Author: "De Waard, A" / Topic: female - Searchworks@Jio Institute Digital Library Search Results

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1. Pre-existing T-cell immunity to SARS-CoV-2 in unexposed healthy controls in Ecuador, as detected with a COVID-19 Interferon-Gamma Release Assay.

Author: Echeverría, Gustavo, Guevara, Ángel, Coloma, Josefina, Ruiz, Alison, Vasquez, María, Tejera, Eduardo, and de Waard, Jacobus
Subjects: COVID-19, ELISPOT, Interferon-Gamma (IFN-γ) release assay (IGRA), Nucleocapsid protein, Pre-existing immunity, SARS-CoV-2, Spike protein, T cells, Adult, COVID-19, Female, Humans, Interferon-gamma Release Tests, Male, Middle Aged, SARS-CoV-2, T-Lymphocytes
Abstract: BACKGROUND: Studies of T-cell immune responses against SARS-CoV-2 are important in understanding the immune status of individuals or populations. Here, we use a simple, cheap, and rapid whole blood stimulation assay - an Interferon-Gamma Release Assay (IGRA) - to study T-cell immunity to SARS-CoV-2 in convalescent COVID-19 patients and in unexposed healthy contacts from Quito, Ecuador. METHODS: Interferon-gamma (INF-γ) production was measured in the heparinized blood of convalescent and unexposed subjects after stimulation for 24 h with the SARS-CoV-2 Spike S1 protein, the Receptor Binding Domain (RBD) protein or the Nucleocapsid (NP) protein, respectively. The presence of IgG-RBD protein antibodies in both study groups was determined with an in-house ELISA. RESULTS: As measured with INF-γ production, 80% of the convalescent COVID-19 patients, all IgG-RBD seropositive, had a strong T-cell response. However, unexpectedly, 44% of unexposed healthy controls, all IgG-RBD seronegative, had a strong virus-specific T-cell response with the COVID-19 IGRA, probably because of prior exposure to common cold-causing coronaviruses or other viral or microbial antigens. CONCLUSION AND DISCUSSION: The high percentage of unexposed healthy subjects with a pre-existing immunity suggests that a part of the Ecuadorian population is likely to have SARS-CoV-2 reactive T-cells. Given that the IGRA technique is simple and can be easily scaled up for investigations where high numbers of patients are needed, this COVID-19 IGRA may serve to determine if the T-cell only response represents protective immunity to SARS-CoV-2 infection in a population-based study.
Published: 2021

2. Lipoarabinomannan antigenic epitope differences in tuberculosis disease subtypes.

Author: Magni, Ruben, Rruga, Fatlum, Alsaab, Fahad M, Sharif, Sara, Howard, Marissa, Espina, Virginia, Kim, Brianna, Lepene, Benjamin, Lee, Gwenyth, Alayouni, Mohamad A, Steinberg, Hannah, Araujo, Robyn, Kashanchi, Fatah, Riccardi, Fabio, Morreira, Sargento, Araujo, Antonia, Poli, Fernando, Jaganath, Devan, Semitala, Fred C, Worodria, William, Andama, Alfred, Choudhary, Alok, Honnen, William J, Petricoin, Emanuel F, Cattamanchi, Adithya, Colombatti, Raffaella, de Waard, Jacobus H, Oberhelman, Richard, Pinter, Abraham, Gilman, Robert H, Liotta, Lance A, and Luchini, Alessandra
Subjects: Humans, Mycobacterium tuberculosis, Tuberculosis, Tuberculosis, Pulmonary, HIV Infections, Lipopolysaccharides, Epitopes, Immunologic Tests, Immunoassay, Sensitivity and Specificity, Adult, Middle Aged, Point-of-Care Systems, Uganda, Guinea-Bissau, United States, Peru, Venezuela, Female, Male, Coinfection
Abstract: An accurate urine test for diverse populations with active tuberculosis could be transformative for preventing TB deaths. Urinary liporabinomannan (LAM) testing has been previously restricted to HIV co-infected TB patients. In this study we evaluate urinary LAM in HIV negative, pediatric and adult, pulmonary and extrapulmonary tuberculosis patients. We measured 430 microbiologically confirmed pretreatment tuberculosis patients and controls from Peru, Guinea Bissau, Venezuela, Uganda and the United States using three monoclonal antibodies, MoAb1, CS35, and A194, which recognize distinct LAM epitopes, a one-sided immunoassay, and blinded cohorts. We evaluated sources of assay variability and comorbidities (HIV and diabetes). All antibodies successfully discriminated TB positive from TB negative patients. ROAUC from the average of three antibodies' responses was 0.90; 95% CI 0.87-0.93, 90% sensitivity, 73.5% specificity (80 pg/mL). MoAb1, recognizing the 5-methylthio-D-xylofuranose(MTX)-mannose(Man) cap epitope, performed the best, was less influenced by glycosuria and identified culture positive pediatric (N = 19) and extrapulmonary (N = 24) patients with high accuracy (ROAUC 0.87, 95% CI 0.77-0.98, 0.90 sensitivity 0.80 specificity at 80 pg/mL; ROAUC = 0.96, 95% CI 0.92-0.99, 96% sensitivity, 80% specificity at 82 pg/mL, respectively). The MoAb1 antibody, recognizing the MTX-Man cap epitope, is a novel analyte for active TB detection in pediatric and extrapulmonary disease.
Published: 2020

3. Cell-autonomous progeroid changes in conditional mouse models for repair endonuclease XPG deficiency.

Author: Barnhoorn, Sander, Uittenboogaard, Lieneke M, Jaarsma, Dick, Vermeij, Wilbert P, Tresini, Maria, Weymaere, Michael, Menoni, Hervé, Brandt, Renata MC, de Waard, Monique C, Botter, Sander M, Sarker, Altaf H, Jaspers, Nicolaas GJ, van der Horst, Gijsbertus TJ, Cooper, Priscilla K, Hoeijmakers, Jan HJ, and van der Pluijm, Ingrid
Subjects: Liver, Central Nervous System, Brain, Animals, Mice, Inbred C57BL, Mice, Transgenic, Osteoporosis, Deficiency Diseases, Disease Models, Animal, Cachexia, Endonucleases, DNA-Binding Proteins, Nuclear Proteins, Transcription Factors, DNA Repair, Aging, Longevity, Pregnancy, Female, Male, Digestive Diseases, Genetics, Liver Disease, Neurosciences, Rare Diseases, 2.1 Biological and endogenous factors, Mice, Inbred C57BL, Transgenic, Disease Models, Animal, Developmental Biology
Abstract: As part of the Nucleotide Excision Repair (NER) process, the endonuclease XPG is involved in repair of helix-distorting DNA lesions, but the protein has also been implicated in several other DNA repair systems, complicating genotype-phenotype relationship in XPG patients. Defects in XPG can cause either the cancer-prone condition xeroderma pigmentosum (XP) alone, or XP combined with the severe neurodevelopmental disorder Cockayne Syndrome (CS), or the infantile lethal cerebro-oculo-facio-skeletal (COFS) syndrome, characterized by dramatic growth failure, progressive neurodevelopmental abnormalities and greatly reduced life expectancy. Here, we present a novel (conditional) Xpg-/- mouse model which -in a C57BL6/FVB F1 hybrid genetic background- displays many progeroid features, including cessation of growth, loss of subcutaneous fat, kyphosis, osteoporosis, retinal photoreceptor loss, liver aging, extensive neurodegeneration, and a short lifespan of 4-5 months. We show that deletion of XPG specifically in the liver reproduces the progeroid features in the liver, yet abolishes the effect on growth or lifespan. In addition, specific XPG deletion in neurons and glia of the forebrain creates a progressive neurodegenerative phenotype that shows many characteristics of human XPG deficiency. Our findings therefore exclude that both the liver as well as the neurological phenotype are a secondary consequence of derailment in other cell types, organs or tissues (e.g. vascular abnormalities) and support a cell-autonomous origin caused by the DNA repair defect itself. In addition they allow the dissection of the complex aging process in tissue- and cell-type-specific components. Moreover, our data highlight the critical importance of genetic background in mouse aging studies, establish the Xpg-/- mouse as a valid model for the severe form of human XPG patients and segmental accelerated aging, and strengthen the link between DNA damage and aging.
Published: 2014

4. Coronary CTA With AI-QCT Interpretation

Author: Isabella Lipkin, Anha Telluri, Yumin Kim, Alfateh Sidahmed, Joseph M. Krepp, Brian G. Choi, Rebecca Jonas, Hugo Marques, Hyuk-Jae Chang, Jung Hyun Choi, Joon-Hyung Doh, Ae-Young Her, Bon-Kwon Koo, Chang-Wook Nam, Hyung-Bok Park, Sang-Hoon Shin, Jason Cole, Alessia Gimelli, Muhammad Akram Khan, Bin Lu, Yang Gao, Faisal Nabi, Ryo Nakazato, U. Joseph Schoepf, Roel S. Driessen, Michiel J. Bom, James J. Jang, Michael Ridner, Chris Rowan, Erick Avelar, Philippe Généreux, Paul Knaapen, Guus A. de Waard, Gianluca Pontone, Daniele Andreini, Mouaz H. Al-Mallah, Tami R. Crabtree, James P. Earls, Andrew D. Choi, James K. Min, Cardiology, ACS - Atherosclerosis & ischemic syndromes, and ACS - Heart failure & arrhythmias
Subjects: Male, Computed Tomography Angiography, CCTA, artificial intelligence, atherosclerosis, coronary CT, coronary CTA, coronary artery disease, fractional flow reserve, quantitative coronary angiography, Myocardial Ischemia, Settore MED/11 - Malattie dell'Apparato Cardiovascolare, Constriction, Pathologic, Coronary Angiography, Predictive Value of Tests, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Aged, Retrospective Studies, Coronary Stenosis, Myocardial Perfusion Imaging, General Medicine, Middle Aged, Reference Standards, Fractional Flow Reserve, Myocardial, Female
Abstract: BACKGROUND. Deep learning frameworks have been applied to interpretation of coronary CTA performed for coronary artery disease (CAD) evaluation. OBJECTIVE. The purpose of our study was to compare the diagnostic performance of myocardial perfusion imaging (MPI) and coronary CTA with artificial intelligence quantitative CT (AI-QCT) interpretation for detection of obstructive CAD on invasive angiography and to assess the downstream impact of including coronary CTA with AI-QCT in diagnostic algorithms. METHODS. This study entailed a retrospective post hoc analysis of the derivation cohort of the prospective 23-center Computed Tomographic Evaluation of Atherosclerotic Determinants of Myocardial Ischemia (CREDENCE) trial. The study included 301 patients (88 women and 213 men; mean age, 64.4 ± 10.2 [SD] years) recruited from May 2014 to May 2017 with stable symptoms of myocardial ischemia referred for nonemergent invasive angiography. Patients underwent coronary CTA and MPI before angiography with quantitative coronary angiography (QCA) measurements and fractional flow reserve (FFR). CTA examinations were analyzed using an FDA-cleared cloud-based software platform that performs AI-QCT for stenosis determination. Diagnostic performance was evaluated. Diagnostic algorithms were compared. RESULTS. Among 102 patients with no ischemia on MPI, AI-QCT identified obstructive (≥ 50%) stenosis in 54% of patients, including severe (≥ 70%) stenosis in 20%. Among 199 patients with ischemia on MPI, AI-QCT identified nonobstructive (1-49%) stenosis in 23%. AI-QCT had significantly higher AUC (all p < .001) than MPI for predicting ≥ 50% stenosis by QCA (0.88 vs 0.66), ≥ 70% stenosis by QCA (0.92 vs 0.81), and FFR < 0.80 (0.90 vs 0.71). An AI-QCT result of ≥ 50% stenosis and ischemia on stress MPI had sensitivity of 95% versus 74% and specificity of 63% versus 43% for detecting ≥ 50% stenosis by QCA measurement. Compared with performing MPI in all patients and those showing ischemia undergoing invasive angiography, a scenario of performing coronary CTA with AIQCT in all patients and those showing ≥ 70% stenosis undergoing invasive angiography would reduce invasive angiography utilization by 39%; a scenario of performing MPI in all patients and those showing ischemia undergoing coronary CTA with AI-QCT and those with ≥ 70% stenosis on AI-QCT undergoing invasive angiography would reduce invasive angiography utilization by 49%. CONCLUSION. Coronary CTA with AI-QCT had higher diagnostic performance than MPI for detecting obstructive CAD. CLINICAL IMPACT. A diagnostic algorithm incorporating AI-QCT could substantially reduce unnecessary downstream invasive testing and costs. TRIAL REGISTRATION. Clinicaltrials.gov NCT02173275.
Published: 2022
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5. A regular contribution from Lars Ovesen, which we hope will help the busy scientist in keeping up with the literature

Author: Meyskens, FL, Jungi, WF, Gerber, M, de Waard, F, Heidemann, E, Heim, ME, Joossens, JV, Salvini, S, Trichopoulou, A, Varela, G, and Wolfram, G
Subjects: Biomedical and Clinical Sciences, Health Sciences, Public Health, Oncology and Carcinogenesis, Animals, Breast Neoplasms, Carcinoma, Diet, Female, Guidelines as Topic, Humans, Risk Factors, World Health Organization, Public Health and Health Services, Oncology & Carcinogenesis, Oncology and carcinogenesis, Public health
Published: 2000

6. WHO consensus conference on diet and cancer. Members of the breast cancer panel.

Author: Meyskens, FL, Jungi, WF, Gerber, M, de Waard, F, Heidemann, E, Heim, ME, Joossens, JV, Salvini, S, Trichopoulou, A, Varela, G, and Wolfram, G
Subjects: Animals, Humans, Carcinoma, Breast Neoplasms, Diet, Risk Factors, World Health Organization, Female, Guidelines as Topic, Oncology & Carcinogenesis, Oncology and Carcinogenesis
Published: 2000

7. Icosapent Ethyl Reduces Ischemic Events in Patients With a History of Previous Coronary Artery Bypass Grafting: REDUCE-IT CABG

Author: Subodh Verma, Deepak L. Bhatt, Ph. Gabriel Steg, Michael Miller, Eliot A. Brinton, Terry A. Jacobson, Nitish K. Dhingra, Steven B. Ketchum, Rebecca A. Juliano, Lixia Jiao, Ralph T. Doyle, Craig Granowitz, C. Michael Gibson, Duane Pinto, Robert P. Giugliano, Matthew J. Budoff, R. Preston Mason, Jean-Claude Tardif, Christie M. Ballantyne, Fabrice M.A.C. Martens, Astrid Schut, Brian Olshansky, Mina Chung, Al Hallstrom, Lesly Pearce, Cyrus Mehta, Rajat Mukherjee, Anjan K. Chakrabarti, Eli V. Gelfand, Megan Carroll Leary, Duane S. Pinto, Yuri B. Pride, Steven Ketchum, Ramakrishna Bhavanthula, Gertrude Chester, Christina Copland, Katelyn Diffin, Ralph Doyle, Kurt Erz, Alex Giaquinto, Paula Glanton, Angela Granger, Richard H. Iroudayassamy, Rebecca Juliano, James Jin, Dimitry Klevak, Hardik Panchal, Robert Wang, Shin-Ru Wang, Gerard Abate, Peggy J. Berry, Rene Braeckman, Declan Doogan, Anne Elson, Amy HauptmannBaker, Isabel Lamela, Catherine Lubeck, Mehar Manku, Sabina Murphy, Monica Sanford, William Stirtan, Paresh Soni, Arnaud Bastien, Demetria Foster, Evangelito Gascon, Judith Johnson, Lasbert Latona, Gang Liu, Sandra Palleja, Nelly Sanjuan, Jimmy Shi, William Stager, Mukund Venkatakrishnan, Ahmed Youssef-Agha, Julie Zhu, Leela Aertker, Suresh Ankolekar, Lisa Goldberg, Natasa Rajicic, Jianfen Shu, Heng Zou, Magdy Mikhail, Gamil Dawood, N. Mathew Koshy, Sandip K. Mukherjee, Rafik Abadier, Andrea L. Lawless, William P. McGuinn, Howard Weintraub, Kathryn Rohr, Edmund Claxton, Robert J. Weiss, Terry D. Klein, Mani Nallasivan, Stephen Crowley, Marilyn King, Anthony D. Alfieri, David Fitz-Patrick, Irving Loh, Nolan J. Mayer, Rakesh Prashad, Samuel Lederman, Debra Weinstein, Harold E. Bays, Keith Chu, Alireza Maghsoudi, Paul D. Thompson, Jeff Carstens, Anna Chang, Kenneth R. Cohen, Julius Dean, Howard S. Ellison, Bernard Erickson, Enrique A. Flores, Daniel W. Gottlieb, Paul Grena, John R. Guyton, Peter H. Jones, John M. Joseph, Norman E. Lepor, Sam Lerman, Robert D. Matheney, Theodore R. Pacheco, Michael B. Russo, John Rubino, Edward S. Pereira, Albert A. Seals, Eduardo Viera, Alan D. Steljes, Jason Thompson, Shaival Kapadia, Michael McIvor, Jorge E. Salazar, Jose O. Santiago, Ralph Vicari, Martin R. Berk, William A. Kaye, Marcus McKenzie, David Podlecki, Brian D. Snyder, Stephen Nash, David M. Herrington, Wallace Johnson, Joseph R. Lee, Ronald Blonder, Alpa M. Patel, Ramon Castello, Susan Greco, Dean J. Kereiakes, Venkatesh K. Nadar, Mark Nathan, Ranganatha P. Potu, Robert Sangrigoli, Richard Smalling, Mitchell Davis, Robert Braastad, James McCriskin, Kunal Bodiwala, Joe L. Hargrove, Mark W. Graves, George Emlein, Raegan W. Durant, James W. Clower, Rohit Arora, Narendra Singh, Lisa Warsinger Martin, W Herbert Haught, Marc P. Litt, Michael D. Klein, Peter Hoagland, Michael Goldstein, Marco S. Mazzella, Daniel H. Dunker, Brian H. Kahn, Carlos S. Ince, Frank A. McGrew, Jay Lee, David Pan, Salman A. Khan, Uri Elkayam, Wasim Deeb, Anne C. Goldberg, Christopher S. Brown, Wayne N. Leimbach, Thomas S. Backer, David R. Sutton, Joel Gellman, Anu R. George, Alan S. Hoffman, Mark Kates, Kishlay Anand, Robert Bear, Brendan J. Cavanaugh, Ramon G. Reyes, Rodolfo Sotolongo, Kenneth Sabatino, Kevin Gallagher, Ehab Sorial, Chris Geohas, Kathleen E. Magness, Bernard P. Grunstra, Frederik A. Martin, William S. Knapp, Mel E. Lucas, John J. Champlin, Jason Demattia, Patrick H. Peters, Judith Kirstein, William J. Randall, Cezar S. Staniloae, Jennifer G. Robinson, Alexander Adler, Christopher Case, Andrew J. Kaplan, Gregory F. Lakin, Krishan K. Goyle, Michael J. DiGiovanna, Chester L. Fisher, Michael Lillestol, Michael Robinson, Robert G. Perry, Lawrence S. Levinson, Brian G. Everhart, Robert D. Madder, Earl F. Martin, Earl E. Martin, Imtiaz Alam, Jose Mari L. Elacion, Robina Poonawala, Taddese T. Desta, Jerome A. Robinson, Gilbert J. Martinez, Jakkidi S. Reddy, Jeffrey D. Wayne, Samuel Mujica Trenche, Westbrook I. Kaplan, Rubin H. Saavedra, Michael D. DiGregorio, Barry D. Bertolet, Neil J. Fraser, Terence T. Hart, Ronald J. Graf, David A. Jasper, Michael Dunn, Dan A. Streja, David J. Strobl, Nan Jiang, Vicki Kalen, Richard Mascolo, Mercedes B. Samson, Michael Stephens, Bret M. Bellard, Mario Juarez, Patrick J. McCarthy, John B. Checton, Michael Stillabower, Edward Goldenberg, Amin H. Karim, Naseem Jaffrani, Robert C. Touchon, Erich R. Fruehling, Clayton J. Friesen, Pradipta Chaudhuri, Frank H. Morris, Robert E. Broker, Rajesh J. Patel, Susan Hole, Randall P. Miller, Francisco G. Miranda, Sadia Dar, Shawn N. Gentry, Paul Hermany, Charles B. Treasure, Miguel E. Trevino, Raimundo Acosta, Anthony Japour, Samuel J. Durr, Thomas Wang, Om P. Ganda, Perry Krichmar, James L. Arter, Douglas Jacoby, Michael A. Schwartz, Amer Al-Karadsheh, Nelson E. Gencheff, John A. Pasquini, Richard Dunbar, Sarah Kohnstamm, Hector F. Lozano, Francine K. Welty, Thomas L. Pitts, Brian Zehnder, Salah El Hafi, Mark A. King, Arnold Ghitis, Marwan M. Bahu, Hooman Ranjbaran Jahromi, Ronald P. Caputo, Robert S. Busch, Michael D. Shapiro, Suhail Zavaro, Munib Daudjee, Shahram Jacobs, Vipul B. Shah, Frank Rubalcava, Mohsin T. Alhaddad, Henry Lui, Raj T. Rajan, Fadi E. Saba, Mahendra Pai N Gunapooti, Tshiswaka B. Kayembe, Timothy Jennings, Robert A. Strzinek, Michael H. Shanik, Pradeep K. Singh, Alastair C. Kennedy, Howard Rubenstein, Ramin Manshadi, Joanne Ladner, Lily Kakish, Ashley Kakish, Amy L. Little, Jaime Gerber, Nancy J. Hinchion, Janet Guarino, Denise Raychok, Susan Budzinski, Kathleen Kelley-Garvin, April Beckord, Jessica Schlinder, Arthur Schwartzbard, Stanley Cobos, Deborah Freeman, David Abisalih, Dervilla McCann, Kylie Guy, Jennifer Chase, Stacey Samuelson, Madeline Cassidy, Marissa Tardif, Jaime Smith, Brenna Sprout, Nanette Riedeman, Julie Goza, Lori Johnson, Chad Kraske, Sheila Hastings, Chris Dutka, Stephanie Smith, Toni McCabe, Kathleen Maloney, Paul Alfieri, Vinay Hosemane, Chanhsamone Syravanh, Cindy Pau, April Limcoiloc, Tabitha Carreira, Taryn S. Kurosawa, Razmig Krumian, Krista Preston, Ashraf Nashed, Daria Schneidman-Fernandez, Jack Patterson, John Tsakonas, Jennifer Esaki, Lynn Sprafka, Porous Patel, Brian Mitchell, Erin M. Ross, Donna Miller, Akash Prashad, Kristina M. Feyler, Natasha Juarbe, Sandra Herrera, Sarah M. Keiran, Becky Whitehead, Whitney Asher, Coury Hobbs, Abbey Elie, Jean Brooks, Amanda L. Zaleski, Brenda Foxen, Barb Lapke, Philippa Wright, Bristol Pavol, Gwen Carangi, Marla Turner, Katharine W. Sanders, Rikita S. Delamar, Virginia L. Wilson, Sarah M. Harvel, Alison M. Cartledge, Kaitlyn R. Bailey, Kathleen Mahon, Timothy Schuchard, Jen Humbert, Mark C. Hanson, Michael P. Cecil, James S. Abraham, Lorie Benedict, Claudia Slayton, Curtis S. Burnett, Rachel W. Ono-Lim, Sharon Budzinski, Shubi A. Khan, Sharon Goss, Terry Techmanski, Farida Valliani, Rimla Joseph, Edith Flores, Laurn Contreras, Ana Aguillon, Carrie-Ann Silvia, Maria Martin, Edmund K. Kerut, Leslie W. Levenson, Louis B. Glade, Brian J. Cospolich, Maureen W. Stein, Stephen P. LaGuardia, Thelma L. Sonza, Tracy M. Fife, Melissa Forschler, Jasmyne Watts, Judy Fritsch, Emese Futchko, Sarah Utech, Scott B. Baker, Miguel F. Roura, Scott A. Segel, James S. Magee, Cathy Jackson, Rebecca F. Goldfaden, Liudmila Quas, Elizabeth C. Ortiz, Michael Simpson, Robert Foster, Christopher Brian, James Trimm, Michael Bailey, Brian Snoddy, Van Reeder, Rachel Wilkinson, Harold Settle, Cynthia Massey, Angela Maiola, Michele Hall, Shelly Hall, Wanda Hall, Mark Xenakis, Janet Barrett, Giovanni Campanile, David Anthou, Susan F. Neill, Steven Karas, Enrique Polanco, Norberto Schechtman, Grace Tischner, Kay Warren, Cynthia St Cyr, Menna Kuczinski, Latrina Alexander, Maricruz Ibarra, Barry S. Horowitz, Jaime Steinsapir, Jeanette Mangual-Coughlin, Brittany Mooney, Precilia Vasquez, Kathleen Rodkey, Alexandria Biberstein, Christine Ignacio, Irina Robinson, Marcia Hibberd, Lisa B. Hoffman, Daniel J. Murak, Raghupathy Varavenkataraman, Theresa M. Ohlson Elliott, Linda A. Cunningham, Heather L. Palmerton, Sheri Poole, Jeannine Moore, Helene Wallace, Ted Chandler, Robert Riley, Farah Dawood, Amir Azeem, Michael Cammarata, Ashleigh Owen, Shivani Aggarwal, Waqas Qureshi, Mohamed Almahmoud, Abdullahi Oseni, Adam Leigh, Erin Barnes, Adam Pflum, Amer Aladin, Karen Blinson, Vickie Wayne, Lynda Doomy, Michele Wall, Valerie Bitterman, Cindi Young, Rachel Grice, Lioubov Poliakova, Jorge Davalos, David Rosenbaum, Mark Boulware, Heather Mazzola, J. Russell Strader, Russell Linsky, David Schwartz, Elizabeth Graf, Alicia Gneiting, Melissa Palmblad, Ashley Donlin, Emily Ensminger, Hillary Garcia, Dawn Robinson, Carolyn Tran, Jeffrey Jacqmein, Darlene Bartilucci, Michael Koren, Barbara Maluchnik, Melissa Parks, Jennifer Miller, Cynthia DeFosse, Albert B. Knouse, Amy Delancey, Stephanie Chin, Thomas Stephens, Mag Sohal, Juana Ingram, Swarooparani Kumar, Heather Foley, Nina Smith, Vera McKinney, Linda Schwarz, Judith Moore, Hildreth Vernon Anderson, Stefano Sdringola-Maranga, Ali Denktas, Elizabeth Turrentine, Rhonda Patterson, John Marshall, Terri Tolar, Donna Patrick, Pamela Schwartzkopf, Anthony M. Fletcher, Frances R. Harris, Sherry Clements, Tiffany Brown, William Smith, Stacey J. Baehl, Robin Fluty, Daniel VanHamersveld, Dennis Breen, Nancy Bender, Beverly Stafford, Tamika Washington, Margaret N. Pike, Mark A. Stich, Evyan Jawad, Amin Nadeem, Jill Nyland, Rhonda Hamer, Kendra Calhoun, Charlotte Mall, Samuel Cadogan, Kati Raynes, Richard Katz, Lorraine Marshall, Rashida Abbas, Jay L. Dinerman, John T. Hartley, Beth Lamb, Lisa Eskridge, Donna Raymond, Kristy Clemmer, Denise M. Fine, Paula Beardsley, Janet Werner, Bette Mahan, Courtney VanTol, Robert Herman, Christine Raiser-Vignola, Felicia McShan, Stefanie A. Neill, David R. Blick, Michael J. Liston, Denetta K. Nelson, Sandra K. Dorrell, Patricia Wyman, Ambereen Quraishi, Fernando Ferro, Frank Morris, Vicki J. Coombs, Autumn M. Mains, Austin A. Campbell, Jeanne Phelps, Cheryl A. Geary, Ellen G. Sheridan, Jean M. Downing, Arie Swatkowski, Tish Redden, Brian Dragutsky, Susan Thomas, Candace Mitchell, Diana Barker, Elanie Turcotte, Deborah Segerson, Jill Guy, Karena De La Mora, Jennifer Hong, Dennis Do, Rose Norris, Faisal Khan, Hector Montero, Stacy Kelly-White, Alan Cleland, Rosalyn Alcalde-Crawford, Melissa Morgan, Brijmohan Sarabu, Megan Minor, Shweta Kamat, Stephanie M. Estes, Nancee Harless, Alicia Disney, Jodi L. Pagano, Chad M. Alford, Noel W. Bedwell, Warren D. Hardy, Kevin DeAndrade, Jessica G. Elmore, Eric Auerbach, Anthony W. Haney, Miriam H. Brooks, Jose Torres, Lois Roper, Terry Backer, Katie Backer, John G. Evans, Ricardo A. Silva, Lorraine H. Dajani, Veronica Yousif, Tammy Ross, Sion K. Roy, Ronald Oudiz, Sajad Hamal, Ferdinand Flores, Amor Leahy, Debra Ayer, Swapna George, Chrisi Carine Stewart, Elvira Orellana, Cristina Boccalandro, Mary Rangel, Suzanne Hennings, Carl Vanselow, Teri Victor, Darlene Birdwell, Paul Haas, Anthony Sandoval, Gina Ciavarella, Caroline Saglam, Amy Bird, Keith Beck, Brian Poliquin, David Dominguez, Brittany Tenorio, Harvonya Perkins, Esther San Roman, Paris Bransford, Christy Lowrance, Marcy Broussard, Mary Ellis, Bobbi Skiles, Jessica Hamilton, Kathryn Hall, Diego Olvera, Julee A. Hartwell, Nevien Sorial, Mary Rickman, Kevin Berman, Nirav Mehta, Annie Laborin, Rodger Rothenberger, Sarah Beauvilliers, Kathy Morrell, Michael P. Schachter, Cindy L. Perkins, Elizabeth A. Gordon, Jennifer Lauer, Kim Bichsel, Kelly Oliver, Leslie J. Mellor, Candice Demattia, Jennifer Schomburg, Yenniffer Moreno, Eduardo Mansur-Garza, Lena Rippstein, Lorie Chacon, Andrea Pena, Michelle King, Susan Richardson, Annette Jessop, Nicole Tucker, Whitney Royer, Gilbert Templeton, Ann Moell, Christine Weller, Melissa J. Botts, Gretel Hollon, Elsa Homberg-Pinassi, Paula Forest, Aref Bin Abhulhak, Devona Chun-Furlong, Deborah Harrington, Emily Harlynn, Marjorie Schmitt, Constance Shelsky, Patricia Feldick, Mary Cherrico, Courtney Jagle, Nicholas Warnecke, Debra Myer, Deanna J. Ruder, Albina Underwood, Alan Rauba, George Carr, Barbara Oberhaus, Jessica Vanderfeltz, Mary Jo Stucky-Heil, Dale R. Gibson, Vonnie Fuentes, Kimberly L. Talbot, William C. Simon, Katlyn J. Grimes, Christina R. Wheeler, Cassaundra Shultz, Rhonda A. Metcalf, Jennifer L. Hill, Michelle R. Oliver, Basharat Ahmad, Fouzal Azeem, Abdul Rahim, George H. Freeman, Dawn Bloch, Heather Freeman, Jamie Brown, Sarah Rosbach, Pamela Melander, Nick Taralson, Alex Liu, Katlyn Harms, Mahfouz Michale, Jose Lopez, Maria Revoredo, Shari Edevane, Sarah Shawley, Timothy L. Jackson, Michael J. Oliver, Dina DeSalle, Patricia J. Matlock, Ionna M. Beraun, Heather Hendrix, Garrett Bromley, Ashley Niemerski, Gabby Teran, Sonia Guerrero, Murtaza Marvi, Zehra Palanpurwala, Andrea Torres, Patty Gloyd, Michelle Conger, Aziz Laurent, Olia Nayor, Catalina S. Villanueva, Munira Khambati, Tabetha J. Mumford, Melanie J. Castillo, Taddese Desta, Jerome Robinson, La Shawn Woods, Anita Bahri, Nancy Herrera, Cecilia Casaclang, Jeffrey R. Unger, Geraldine Martinez, Mia K. Moon, Stephen M. Mohaupt, Larry Sandoval, Louisito Valenzuela, Victora Ramirez, Nelly Mata, Veronica Avila, Marisol Patino, Cynthia Montano-Pereira, Omar Barnett, William M. Webster, Lorraine M. Christensen, Leighna Bofman, Melanie Livingston, Stacey Adams, Joseph Hobbs, Leesa Koskela, Mia Katz, Samuel Mujica-Trenche, Franklin Cala, Noreen T. Rana, Jennifer Scarlett, Milagros Cala Anaya, Marsha R. Jones, Kelly D. Hollis, Debbie Roth, Kristin Eads, Tina Watts, Judy Perkins, Alice Arnold, Daniel C. Ginsberg, Denise Quinn, Nicole Cureton, David B. Fittingoff, Mohammed I. Iqbal, Stephen R. White, Edith Sisneros, Michelle Ducca, David Streja, Danny Campos, Jennifer L. Boak, Farzeen Amir, Felice Anderson, James J. Kmetzo, Mary O. Bongarzone, Dawn Scott, Mary Grace De Leon, Cynthia Buda, William Graettinger, Michelle Alex, Erika Hess, James Govoni, Melissa Bartel, Travis L. Monchamp, Julie S. Roach, Sara Gibson, Amy M. Allfrey, Kristen Timpy, Kathy Bott, Karin A. Soucy, Jean Willis, Cecilia A. Valerio, Anusha Chunduri, Rebecca Coker, Nicole Vidrine, Ellen A. Thompson, Mark A. Studeny, Melissa K. Marcum, Tammy S. Monway, Douglas L. Kosmicki, Melissa J. Kelley, Corey M. Godfrey, Susan L. Krenk, Randy R. Holcomb, Deb K. Baehr, Mary K. Trauernicht, David Rowland Lowry, Betty Bondy Herts, Jeanne E Phelps, Jean-Marie Downing, Carol Gamer Dignon, Elisabeth S. Cockrill, Pravinchandra G. Chapla, Diane Fera, Margaret Chang, Patricia Fredette, Tamie Ashby, Renee Bergin, Zebediah A. Stearns, David B. Ware, Rachael M. Boudreaux, Joanna Rodriguez, Robert McKenzie, Amanda Huber, Rebecca Sommers, Heather Rowe, Stacy McLallen, Michale Haynes, Ashley Adamson, Janice Henderson, Lori McClure, Beverly A. Harris, Laura Ference, Sue Meissner-Dengler, Lisa Treasure, Doreen Nicely, Timothy L. Light, Tracey A. Osborn, Kimberly J. Mai, Pablo Vivas, Jose Rios, Dunia Rodriguez, Roger DeRaad, James Walder, Oscar Bailon, Denice Hockett, Debbie Anderson, Kelli McIntosh, Amber Odegard, Andrew Shepherd, Mary Seifert, Laurence Kelley, Rajendra Shetty, Michael Castine, David Brill, Gregory Fisher, Nicole Richmond, Kathleen Gray, Patricia Miller, Charlene Coneys, Yarixa Chanza, Monica Sumoza, Victoria M. Caudill, Kelly D. Harris, Courtney A. Manion, Melody J. Lineberger-Moore, Julie J. Wolfe, Barbara J. Rosen, Patricia DiVito, Janet L. Moffat, Christina Michaelis, Prashant Koshy, Diana Perea, Ghaith Al Yacoub, Stephanie Sadeghi, Thomas D. LeGalley, Rudolph F. Evonich, William J. Jean, Gary M. Friesen, John M. Pap, David A. Pesola, Mark D. Cowan, Kristofer M. Dosh, Dianna Larson, Adele M. Price, Jodi A. Nease, Jane E. Anderson, Lori A. Piggott, Robert Iwaoka, Kevin Sharkey, Edward McMillan, Laurie Lowder, Latisha Morgan, Kyle Davis, Tara Caldwell, Erica Breglio, Jasmine Summers, Rachel Poulimas, Muhammad Zahid, Hamid Syed, Maria Escobar, Jacob Levy, Rahma Warsi, Carol Ma, Puxiao Cen, Kimberly A. Cawthon, Delores B. Barnes, Deanna G. Allen, Margaret L. Warrington, Carol R. Stastny, Robin J. Michaels, Mohamad Saleh, John Sorin, Sunny Rathod, Urakay Juett, Steven Spencer, Aziza Keval, Jill McBride, Shane Young, Catherine Baxter, Carol Rasmussen, Shari L. Coxe, Luis Campos, Shahin Tavackoli, Diana Beckham, Darlynee Sanchez, Karanjit Basrai, Dorian Helms, Erica Clinton, Kasie Smith, Henry Cusnir, Mary Klaus Clark, Madhavagopal V. Cherukuri, Ameta Scarfaru, Stephen D. Nash, Loretta C. Grimm, Anna Grace, Kylie McElheran, Dino Subasic, Zedrick Buhay, Janet Litvinoff, Deepak Shah, Shannon Cervantes, Freda Usher, Farra Yasser, Theodore Trusevich, Ronnie L. Garcia, Jamison Wyatt, Rahul Bose, Holllilyn Miska, Traci Spivey, Amy B. Wren, Katie E. Vance, Lani L. Holman, Pam Gibbons, Elaine Eby, Sandra Shepard, Soratree Charoenthongtrakul, Brett Snodgrass, Mohammed Nazem, Shelly Keteenburg, Prathima Murthy, Frederic Prater, Ashley Rumfelt, Christina Eizensmits, Lisa Iannuzzi, Pourus R. Patel, Clellia Bergamino, Elizabeth McFeaters, Botros Rizk, Emiljia Pflaum, Danny Kalish, Rex Ambatali, Mona Ameli, Delaina Sanguinetti, Rakesh Vaidya, Martinus A.W. Broeders, Dorman Henrikus, Adrianus F.M. Kuijper, Nadea Al-Windy, Michael Magro, Karim Hamraoui, Ismail Aksoy, Guy L.J. Vermeiren, H.W.O. Roeters van Lennep, Gerard Hoedemaker, Johannes Jacobus Remmen, Kjell Bogaard, Dirk van der Heijden, Nicole MJ Knufman, Joost Frederiks, Johannes Willem Louwerenburg, Piet van Rossum, Johannes Milhous, Peter van der Meer, Arno van der Weerdt, Rob Breedveld, Mitran Keijzers, Walter Hermans, Ruud van de Wal, Peter A.G. Zwart, Marc M.J.M. van der Linden, Gerardus Zwiers, Dirk J. Boswijk, Jan Geert Tans, Jacob van Eck, Maarten V. Hessen, Barnabas J.B. Hamer, Stieneke Zoet-Nugteren, Lucien Theunissen, E.A. van Beek, Remco Nijmeijer, Pieter R. Nierop, Gerard Linssen, H.P. Swart, Timo Lenderink, Gerard L. Bartels, Frank den Hartog, Brian J. Berg van den, Wouter van Kempen, Susanne Kentgens, Gloria M. Rojas Lingan, Martinus M. Peeters, Hilligje Keterberg, Melchior Nierman, Annemieke K. den Hollander, Jacqueline Hoogendijk, Christine Voors-Pette, Vicdan Kose, Peter Viergever, Larysa Yena, Viktor Syvolap, Mykola P. Kopytsya, Olga Barna, Svitlana S. Panina, Mykhailo I. Lutai, Oxana V. Shershnyova, Iryna Luzkiv, Larysa S. Bula, Sergii Zotov, Ivan Vyjhovaniuk, Olena Lysunets, Volodymyr I. Koshlia, Nataliya Sydor, Myroslava F. Vayda, Olexiy Ushakov, Mykola Rishko, Viktor P. Shcherbak, Yevgeniya Svyshchenko, Vira Tseluyko, Andriy Yagensky, Viktoriia I. Zolotaikina, Olga Godlevska, Larysa Ivanova, Olena Koval, Olena I. Mitchenko, Galyna Y. Kardash, Yurii S. Rudyk, Mykola Stanislavchuk, Volodymyr Ivanovych Volkov, Olena G. Karlinskaya, Susanna A. Tykhonova, Nikolay Vatutin, Ganna Smirnova, Volodymyr M. Kovalenko, Viktor Lizogub, Denys Sebov, Oleksandr Dyadyk, Svetlana Andrievskaya, Mykola P. Krasko, Alexander N. Parkhomenko, Lidiya Horbach, Iryna G. Kupnovytska, Tetyana Pertseva, Oleksandr Karpenko, Dmytro Reshotko, Svitlana V. Zhurba, Leonid Rudenko, Viktoriia Yu Zharinova, Valerii B. Shatylo, Yuriy I. Karpenko, Mariya A. Orynchak, Tatiana R. Kameneva, Elena Zherlitsina, Diana N. Alpenidze, Grigoriy P. Arutyunov, Elena Baranova, Boris Bart, Dmitriy I. Belenkiy, Svetlana A. Boldueva, Elena A. Demchenko, Vera V. Eltishcheva, Alexander M. Gofman, Boris M. Goloshchekin, Ivan Gennadyevich Gordeev, Nikolay Gratsianskiy, Gadel Kamalov, Niyaz R. Khasanov, Irina M. Kholina, Zhanna D. Kobalava, Elena V. Kobeleva, Alexandra O. Konradi, Victor A. Kostenko, Andrey Dmitrievich Kuimov, Polina Y. Ermakova, Sofia K. Malyutina, Alexey V. Panov, Natalia V. Polezhaeva, Olga Reshetko, Nataliya P. Shilkina, Sergey B. Shustov, Elena A. Smolyarchuk, Raisa I. Stryuk, Elena Yurievnar Solovieva, Andrey V. Susekov, Natalia Vezikova, Svetlana N. Ivanova, Alexander A. Petrov, Vladimir O. Konstantinov, Alina S. Agafina, Victor Gurevich, Konstantin N. Zrazhevskiy, Tatiana V. Supryadkina, Nikita B. Perepech, Vadim L. Arkhipovskiy, Dmitry Yu Butko, Irina A. Zobenko, Olga V. Orlikova, Viktor Mordovin, Olga L. Barbarash, Anastasiya Lebedeva, Vladimir Nosov, Oleg V. Averkov, Elena P. Pavlikova, Yuri B. Karpov, Marina Lvovna Giorgadze, Oleg A. Khrustalev, Mikhail Arkhipov, Tatiana A. Raskina, Julia V. Shilko, Yulia Samoilova, Elena D. Kosmacheva, Sergey V. Nedogoda, Kathleen Coetzee, Lesley J. Burgess, F.C.R. Theron, Iftikhar O. Ebrahim, Gerbrand A. Haasbroek, Maria Pretorius, Julien S. Trokis, Dorothea V. Urbach, Mark J. Abelson, Adrian R. Horak, Aysha E. Badat, Ellen M. Makotoko, Hendrik Du Toit Theron, Padaruth Ramlachan, Clive H. Corbett, Ismail H. Mitha, Hendrik F.M. Nortje, Dirkie J. Jansen van Rensburg, Peter J. Sebastian, F.C.J. Bester, Louis J. van Zyl, Brian L. Rayner, Elżbieta Błach, Magda Dąbrowska, Grzegorz Kania, Agata E. Kelm-Warchol, Leszek P. Kinasz, Janusz Korecki, Mariusz Kruk, Ewa Laskowska-Derlaga, Andrzej Madej, Krzysztof Saminski, Katarzyna Wasilewska, Katarzyna Szymkowiak, Małgorzata Wojciechowska, Natalia Piorowska, Andrzej Dyczek, Rajpal K. Abhaichand, Ramesh B. Byrapaneni, Basavanagowdappa Hattur, Malipeddi Bhaskara Rao, Nitin Ghaisas, Sujit Shankar Kadam, Jugal B. Gupta, Santhosh M. Jayadev, V.A. Kothiwale, Atul Mathur, Vijay Bhaskar, Ravi K. Aluri, Udaya P. Ponangi, Mukesh K. Sarna, Sunil Sathe, Manish K. Sharma, Jilendra Pal Singh Sawhney, Chakrabhavi B. Keshavamurthy, Arun Srinivas, Hemant P. Thacker, A. Sharda, Johny Joseph, Sunil Dwivedi, Viswanathan Mohan, Rajendra K. Premchand, Jacques Bedard, Jean Bergeron, Ronald Collette, David Crowley, Richard Dumas, Sam Henein, Geoff Moran, William F. O’Mahony, Michael O’Mahony, Sammy Chan, Mark H. Sherman, Graham C. Wong, Brian D. Carlson, Milan K. Gupta, David Borts, Sean R. Peterson, Martyn Chilvers, Allan J. Kelly, Jean C. Gregoire, Simon Kouz, Josep Rodés Cabau, Minodora Andor, Mircea Cinteza, Radu Ciudin, Radu I. Cojan, Roxana O. Darabont, Dan-Lucian Dumitrascu, Carmen Fierbinteanu-Braticievici, Ana Gabriela Fruntelata, Constantin Militaru, Bogdon E. Minescu, Doina Luminita Serban, Florin Mitu, Dorel Nastase Melicovici, Ovidiu Petrascu, Octavian M. Pirvu, Cristian Podoleanu, Calin Pop, Rodica-Valentina V. Stanescu-Cioranu, Adrian Tase, Cristina Voiculet, Constantine N. Aroney, Anthony M. Dart, Timothy Davis, Karam Kostner, David N. O’Neal, Peter W. Purnell, Bhuwanendu B. Singh, David R. Sullivan, Peter Thompson, Gerald F. Watts, Adam F. Blenkhorn, John V. Amerena, Rafeeq Samie, Randall Hendriks, Joseph Proietto, Nikolai Petrovsky, Alan Whelan, David Colquhoun, Russell S. Scott, Simon C. Young, Tammy Pegg, Samuel JS Wilson, Andrew W. Hamer, Richard A. Luke, Hamish H. Hart, Gerard P. Devlin, Gerard T. Wilkins, Ian F. Ternouth, Samraj Nandra, Bruno S. Loeprich, Nicole McGrath, Stuart L. Tie, Rob J. Bos, Alexandra Wils, Tamara Jacobs, Erik A. Badings, Lillian A. Ebels-Tuinbeek, Mayke L. Scholten, Esther Bayraktar-Verver, Debby Zweers, Manoek Schiks, Carolien Kalkman, Tineke Tiemes, Jeanette Mulderij, Katarzyna Dabrowska, Wilma Wijnakker, Riny Van de Loo, Jeanne de Graauw, Giny Reijnierse, Mirjam van der Zeijst, Mariska Scholten, Henk R. Hofmeijer, Antoinette van Dijk-van der Zanden, Dineke J. van Belle, Jan Van Es, Gera Van Buchem, Wendy Zijda, Harald Verheij, Linnea Oldenhof-Janssen, Martina Bader, Marije Löwik, Sandra Stuij, Pascal Vantrimpont, Krista van Aken, Karen Hamilton, Han Blömer, Gabriela van Laerhoven, Raymond Tukkie, Maarten Janssen, Gerard Verdel, Jon Funke Küpper, Bob van Vlies, Caroline Kalkman, Joke Vooges, Marinella Vermaas, Rachel Langenberg, Niek Haenen, Frans Smeets, Arko Scheepmaker, Marcel Grosfeld, Ilvy Van Lieshout, Marleen van den Berg, Marian Wittekoek, Petra Mol, Antionette Stapel, Margaretha Sierevogel, Nancy van der Ven, Annemiek Berkelmans, Eric Viergever, Hanneke Kramer, Wilma Engelen, Karen V. Houwelingen, Thierry X. Wildbergh, Arend Mosterd, Coriet Hobé-Rap, Marjan van Doorn, Petra Bunschoten, Michel Freericks, Mireille Emans, Petra Den Boer-Penning, Els Verlek, Christine Freericks, Cornelis de Nooijer, Christina Welten, Ingrid Groenenberg, Claudia van der Horst, Esther Vonk, Geert Tjeerdsma, Gerard M. Jochemsen, Corinne van Daalen, Ingrid Y. Danse, Lucy Kuipers, Anke Pieterse, Antonius Oomen, Daan de Waard, Willem Jan Flu, Zusan Kromhout, Petra Van der Bij, Rob Feld, Brigitta Hessels-Linnemeijer, Rob Lardinois, Jan L. Posma, Zwanette R. Aukema-Wouda, Marjolijn Hendriks-van Woerden, Desiree van Wijk, Driek P. Beelen, Ingrid H. Hendriks, Jan J. Jonker, Stefanie Schipperen, Vicdan Köse, Gloria Rojas, Linda Goedhart, Hanneke van Meurs, Jacqueline Rijssemus, Lindy Swinkels-Diepenmaat, Marloes de Louw-Jansen, Dominique Bierens-Peters, Willem W. van Kempen, Marianne E. Wittekoek, Irmaina Agous, Geert Schenk, Janneke Wittekoek, Kevin Cox, Deborah F. Julia, Jan J.C. Jonker, Roel Janssen, Melchor Nierman, Hilligje Katerberg, Irene van der Haar, Willem W. Van Kempen, Taco van Mesdag, Leyda M. Alvarez Costa, Manon Schensema, Salomé Zweekhorst, Deborah Font Julia, Lauri Hanewinckel, Joyce Olsthoorn, Johan C. Berends, Arie C. van der Spek, Roy van der Berg, Rob J. Timmermann, Ingrid Boerema, Iryna Mudruk, Anna Khrystoforova, Serhii Kyselov, Yaroslava V. Hilova, Pavlo Logoida, Nataliia A. Sanina, Ilona P. Golikova, Olena O. Nemchyna, Ivan I. Isaichikov, Olga B. Potapova, Iurii V. Gura, Larysa Berestetska, Olena O. Kulianda, Oleksandr Tantsura, Oleksandr S. Kulbachuk, Volodymyr Petsentiy, Ihor Biskub, Tetyana Handych, Oleg Lagkuti, Alyna Gagarina, Taras Chendey, Oksana F. Bilonko, Olena Matova, Larysa Bezrodna, Olena Yarynkina, Tetiana Ovdiienko, Volodymyr Randchenko, Maryna Mospan, Olena Butko, Olga Romanenko, Mykhailo Pavelko, Iryna Sichkaruk, Svitlana O. Lazareva, Olena A. Kudryk, Inessa M. Koltsun, Tetiana Magdalits, Sergei Zadorozhniy, Kira Kompaniiets, Andrii Ivanov, Sergiy Romanenko, Pavlo Kaplan, Vadym Y. Romanov, Oksana P. Mykytyuk, Nataliia S. Zaitseva, Sergiy N. Pyvovar, Lyudmyla Burdeuna, Emerita Serdobinska, Tatiana I. Shevchenko, Igor I. Ivanytskyi, Olena V. Khyzhnyak, Nataliya Kalinkina, Olena Keting, Olena Sklyanna, Olga Kashanska, Anna Shevelok, Marina Khristichenko, Ievgenii Y. Titov, Danilenko O. Oleksander, Nataliia S. Polenova, Nataliia Altunina, Viktoriia Kororaieva, Stanislav Zborovskiy, Leonid Kholopov, Iurii Suliman, Lanna Lukashenko, Stanislav Shvaykin, Olexandr M. Glavatskiy, Roman O. Sychov, Roman L. Kulynych, Oleksandr A. Skarzhevskyi, Nataliia V. Dovgan, Marta Horbach, Olga Cherkasova, Iryna Tyshchenko, Liudmyla Todoriuk, Svitlana Kizim, Nataliia Brodi, Oleksandr Ivanko, Olga Garbarchuk, Liudmyla Alieksieieva, Tetiana L. Shandra, Olena Beregova, Larisa An Bodretska, Svitlana S. Naskalova, Ivanna A. Antoniuk-Shcheglova, Olena V. Bondarenko, Natalia G. Andreeva, Iryna I. Vakalyuk, Olha S. Chovganyuk, Nataliya R. Artemenko, Kiril A. Maltsev, Natalia Kalishevich, Natalia G. Kondratyeva, Svetlana A. Nikitina, Maria V. Martjanova, Anna V. Sokolova, Dmitrii O. Dragunov, Olga Kolesnik, Vera Larina, Oxana V. Tsygankova, Maria Ivanova, Illia A. Karpov, Elena M. Aronova, Ekaterina S. Vedernikova, Ekaterina I. Lubinskaya, Taras Y. Burak, Sergey I. Skichko, Farhad Rasulev, Ekaterina B. Soldatova, Alexander L. Fenin, Ilya I. Laptev, Elena E. Luchinkina, Alexandr Akatov, Natalia V. Polenova, Natalia N. Slavina, Irina N. Korovnika, Marina Yu Prochorova, Regina Shakirova, Elena N. Andreicheva, Olga A. Krasnova, Tinatin V. Lobzhanidze, Tatiana B. Dmitrova, Viktoriya V. Stakhiv, Maria I. Pechatnikova, Alexandra V. Panova, Maria Y. Tipikina, Oxana P. Rotar, Nikolay A. Bokovin, Saule K. Karabalieva, Farid Y. Tumarov, Elena V. Vasileva, Natalya Gennadevna Lozhkina, Ekaterina V. Filippova, Alisa I. Sharkaeva, Ekanerina V. Filippova Deilik, Natalia Yu Tolkacheva, Elena N. Domracheva, Andrey N. Ryabikov, Inga T. Abesadze, Marianna Z. Alugishvili, Elena P. Nikolaeva, Nadezda V. Smirnova, Valentina I. Rodionova, Polina V. Dolovstaya, Igor E. Yunonin, Sergey V. Kadin, Tatyana S. Sveklina, Anna V. Bushmanova, Elena L. Barkova, Irina S. Gomova, Yana V. Brytkova, Tatiana B. Ivanova, Marina Y. Zubareva, Inga Skopets, Lybov A. Galashevskaya, Emilia D. Butinskaya, Olga G. Gusarova, Natalia B. Kalishevich, Yana R. Pavlova, Marianna P Serebrenitskaya, Vitalina F. Grygorieva, Gulnara R. Kuchaeva, Inna A. Vasileva, Gulnara I. Ospanova, Yulia V. Vahrusheva, Irina A. Semenova, Irina E.E. Mikhailova, Olga O. Kvasova, Valeria D. Shurygina, Alexey E. Rivin, Alexey O. Savelyev, Alexey A. Savelyev, Olesya O. Milyaeva, Nadezhda N. Lapshina, Ninel A. Lantsova, Pavel V. Alexandrov, Evgeniy A. Orlikov, Alla Falkovskaya, Tatiana Ripp, Sergei Triss, Stanislav Pekarskiy, Sitkova Ekaterina, Evgeniya N. Zhuravleva, Olga Perova, Galina Kovaleva, Liubov Koroleva, Lydia Mishchenko, Boris P. Garshin, Svetlana A. Kutuzova, Lyudmila I. Provotorova, Igor P. Zadvorny, Olga V. Okhapkina, Anatoly O. Khrustalev, Tatiana Suvorova, Elena S. Shaf, Varvara A. Vershinina, Andrey A. Kozulin, Oxana A. Oleynik, Irina Y. Martynova, Natalia V. Kizhvatova, Alla S. Salasyuk, Vera V. Tsoma, Alla A. Ledyaeva, Elena V. Chumachek, S.C. Blignaut, Tersia Y. Alexander, Chano Du Plessis, Thirumani Govender, Samatha M. Du Toit, Leya Motala, Areesh Gassiep, Christina Naude (Smit), Marli Terblanche, Marlien Snoer (Kruger), Berenice Pillay, De Vries Basson, Marisa E. Theron, Bianca Fouche, Mareli E. Coetzee, Pieter Odendall, Frederik H. Van Wijk, Anna-Mari Conradie, Trudie Van der Westhuizen, Carine Tredoux, Mohamed S. Mookdam, Andie J. Van der Merwe, Karin Snyman, Gerda Smal, Yvonne De Jager, Thomas A. Mabin, Annusca King, Lindy L. Henley, Brenda M. Zwane, Jane Robinson, Marinda Karsten, Andonia M. Page, Valerie Nsabiyumva, Charmaine Krahenbuhl, Jaiprakash D. Patel, Yunus E. Motala, Ayesha Dawood, Nondumiso B. Koza, Lenore M.S. Peters, Shavashni Ramlachan, Wilhelm J. Bodenstein, Pierre Roux, Lizelle Fouche, Cecilia M. Boshoff, Haroon M. Mitha, Fathima Khan, Henry P. Cyster, Helen Cyster, E. C. Wessels, Florence J. Jacobs, Melanie A. Sebastian, Deborah A. Sebastian, Nadia Mahomed, Ignatius P. Immink, Celia Cotzee, Tanja Cronje, Madele Roscher, Maria Le Roux, Yvonne A. Trinder, Renata Wnętrzak-Michalska, Magdalena Piszczek, Andrzej Piela, Ewa Czernecka, Dorota Knychas, Alina Walczak, Izabella Gładysz, Katarzyna Filas, Ewelina Kiluk, Krzysztof Świgło, Iwona Jędrzejczyk, Kamila Łuczyńska, Katarzyna Tymendorf, Wojciech Piesiewicz, Wojciech L. Kinasz, Stefan Samborski, Ilona Bartuś, Gramzyna Latocha Korecka, Ewa Gulaj, Jolanta Sopa, Bogusław Derlaga, Marcin Baisiak, Allicia Kowalisko, Edyta Stainszewska-Marasazlek, Bartosz Szafran, Malgorzata Swiatkiewicz, Artur Racewicz, Sławomir Grycel, Jerzy Supronik, Sylwia Walendziuk, Magdalena Tarantowicz, Agata Stasiak, Anna Sidorowicz-Białynicka, Marek Dwojak, Ewa Jaźwińska-Tarnawska, Katarzyna Kupczyk, Kamila Martowska, Kamila Kulon, Katarzyna Gajda, Bivin Wilson, Krithika Velusamy, Swaidha S. Sadhiq, Bhavani Siddeshi, M. Bhanukumar, Abhishek Srivatsav, Madhan Ramesh, Sri Harsha Chalasani, Mini Johnson, Prashanth Gopu, Jeesa George, Sowmya Reddy, Swetha Tessy Thara Eleena, Damodara Rao Kodem, Haritha N. Nakkella, Padma Kumari Mandula, Anjan Kumar Vuriya, Syamala Rajana, Aruna Kale, Tiwari Rajeev, Raina Jain, Vipin Jain, Srilakshmi Mandayam Adhyapak, Lumin Sheeba, Uma C R, Ramya R, Aditya V. Kulkarni, M.S. Ganachari, Ruma Sambrekar, Mohammad Bilal, Kalyan Chakravarthy, Ravi Badhavath, Sravan Kumar, Meenakshi Simhadri, Farooque Salamuddin, Venkat Prasad, Vivek Dwivedi, Sudha Sarna, Tilak Arora, Deepak Chawla, Archana Sathe, Chaware Gayatree, Ajeet Nanda, Ram Avtar, Jyoti Sharma, Vaibhavi P S, Sasirekha D, Deepthi Kobbajji, Ramya Ningappa, Shwetha Shree, Chandrashekar K, Nandini M R, Sowjanya S, Devika I G, Yashaswini N, Sonika G, Rathna L, Priyanka R, Rupal J. Shrimanker, Lakshmi Vinutha Reddy, K. Sumathi, Babitha Devi, Bina N. Naik, Rohini Manjunath, Rajeshwari Ashok, Tony V. Kunjumon, Jesline Thomas, Shaik Samdhani, Kasthuri Selvam, Poongothai Subramani, Nandakumar Parthasarathy, Nirmal K. Bohra, Anvesh K. Gatla, Cheryl Horbatuk, Julie Sills, E B. Davey, Liz Paramonczyk, Olga Racanelli, Sandy Strybosch, Andre Belanger, Jean Palardy, Alicia Schiffrin, Sylvie Gauthier, Norman Kalyniuk, Shawn D. Whatley, Heather Lappala, Grishma Patel, Matthew Reeve, Catherine Moran, Jody Everitt, Teresa Ferrari, Christine Bouffard, Jirir Frohlich, Gordon Francis, John Mancini, Gregory Bondy, Debbie DeAngelis, Patricia Fulton, David W. Blank, Angela Lombardo, Mylène Roy, Jackie Chow, Hyman Fox, William J. Grootendorst, Angela Hutchinson, Sharon M. Chan, Christie Fitzgerald, Lynn Wilkins, Rebecca L. Raymond, Arlene Reyes, Lavoie Marc André, Denis Fortin, Hélène Ouimet, Thanh-Thao Tôn-Nu, Martine Dussureault, Marie-Hélène Blain, Madeleine Roy, Nathalie Kopajko, Chantal Fleury, Karine Maheux, Gabriela Valentina Ciobotaru, Maria C. Constantinescu, Carmen-Lucia Gherghinescu, Ana-Maria Avram, Ioan Manitiu, Aura Sinpetrean, Lucian Pop, Delia Lupu, Radu Usvat, Ana Petrisor, Nicoleta Dumitru, Camelia Moruju, Adelina Gheorghita, Magda V. Mitu, Cosmin Macarie, Ana Maria Pop, Maria-Catalina Diaconu, Iulia Grancea, Mihaela Cosma, Mihaela Crisan, Elizabeth Herron, Paul Nestel, Sally B. Kay, Kaye S. Carter, Imran Badshah, Ashley Makepeace, Jocelyn Drinkwater, Michelle England, Azette Rafei, Kylie Patterson, Alicia Jenkins, Sybil McAuley, Sue M. Kent, Joy E. Vibert, Leonie Perrett, Thomas David, Samantha L. Kaye, Monika O’Connor, Nimalie J. Perera, Nicole T. Lai, Kerry A. Kearins, Christinia Dicamillo, Heather Anderson, Louise Ferguson, Sharon D. Radtke, Charles T. Thamarappillil, Janice M. Boys, Anita K. Long, Toni Shanahan, Michael Nyguyen, Nicole Forrest, Gill Tulloch, Della Greenwell, Sarah L. Price, Aye N. Tint, Priya K. Sumithran, Tamara L. Debreceni, Lisa Walker, Mary Caruana, Kira Edwards, Maria Stathopoulos, Cilla Haywood, Dimitar Sajkov, Sharen Pringle, Anne Tabner, Kathrina Bartolay, Chamindi Abeyratne, Kylie Bragg, Patrick Mulhern, Peter Purnell, Lyn Williams, Jane Hamlyn, Aurelia Connelly, Jan Hoffman, Samantha Bailey, Jane Kerr, Zarnia Morrison, Sarah Maeder, Roberta McEwan, Prasanna Kunasekera, Patrice McGregor, Jo Young, Sharon Berry, Rick Cutfield, Michelle Choe, Catherine McNamara, Narrinder K. Shergill, Petra Crone, Miles G. Williams, Keith Dyson, Diana H. Schmid, Audrey C. Doak, Melissa Spooner, Colin Edwards, Anne Turner, Grainne M. McAnnalley, Raewyn A. Fisher, Fraser B. Hamilton, Denis H. Friedlander, Melissa R. Kirk, Jayne E. Scales, Marguerite A. McLelland, Neelam A. Dalman, Cathy E. Vickers, Carolyn Jackson, Wendy Coleman, Phillip I. Garden, and Wendy F. Arnold
Subjects: Male, medicine.medical_specialty, Rate ratio, Double-Blind Method, Ischemia, Risk Factors, Physiology (medical), Internal medicine, medicine, Clinical endpoint, Humans, Myocardial infarction, Coronary Artery Bypass, Stroke, Aged, business.industry, Unstable angina, Hazard ratio, Absolute risk reduction, Middle Aged, medicine.disease, Eicosapentaenoic Acid, Number needed to treat, Cardiology, Female, Cardiology and Cardiovascular Medicine, business
Abstract: Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.
Published: 2021
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8. Preferences and Experiences Regarding the Use of the Self-Sampling Device in hrHPV Screening for Cervical Cancer

Author: Geertruida H. de Bock, Karin M. Vermeulen, Marjolein Dieleman, Ed Schuuring, Jolien de Waard, Martha D. Esajas, G. Bea A. Wisman, Targeted Gynaecologic Oncology (TARGON), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Value, Affordability and Sustainability (VALUE), Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), and Life Course Epidemiology (LCE)
Subjects: Cervical cancer, medicine.medical_specialty, Cervical screening, Health economics, Public health, Papillomavirus Infections, MEDLINE, Uterine Cervical Neoplasms, WOMEN, medicine.disease, Health administration, Test (assessment), ACCEPTABILITY, Family medicine, medicine, Humans, Mass Screening, Female, Psychology, Papillomaviridae, Early Detection of Cancer, Qualitative research
Abstract: Background To improve participation in the Dutch cervical cancer screening, a self-sampling device (SSD) was introduced in 2017 into the Dutch population-based screening programme (PBS) for the early detection of cervical cancer. The aim of this study was to gather potential preferences and experiences that might influence a woman's decision to use the SSD in the Dutch PBS. Methods A scoping review was performed in the PubMed database. Studies that assessed preferences and experiences of women regarding the SSD were included, and preferences and experiences were extracted. In addition, in a qualitative study, the list of potential preferences and experiences specific for the Dutch PBS was extended based on semi-structured interviews with SSD users as well as non-SSD users who recently participated in the PBS, analysed in a structured manner by translating full sentences to key words. Results Ninety-eight studies were included in the scoping review and 16 interviews were performed. Frequently mentioned reasons for using the SSD, in both the interviews and the literature, were practicality and comfort. Frequently mentioned reasons for not using the SSD were fear of not performing the SSD procedure correctly and doubts on whether the results of the high-risk human papillomavirus (hrHPV) test will be reliable. A new positive experience elicited in the interviews was accessibility. Negative preferences and experiences were not being aware the SSD was an option, and the inconvenience that after an hrHPV-positive test result of the SSD, an additional smear test at the GP is necessary. Conclusion Several preferences and experiences play a role in the choice whether or not to use the SSD. Based on the currently found preferences and experiences, an app will be developed in order to assess which of these are the most important for women participating in the Dutch population-based cervical screening programme.
Published: 2021
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9. Hypoxia-Inducible Factor 1 and Preeclampsia: A New Perspective

Author: Sarah M, Albogami, Hayder M, Al-Kuraishy, Thabat J, Al-Maiahy, Ali K, Al-Buhadily, Ali I, Al-Gareeb, Mohammed, Alorabi, Saqer S, Alotaibi, Michel, De Waard, Jean-Marc, Sabatier, Hebatallah M, Saad, and Gaber El-Saber, Batiha
Subjects: Oxygen, Pre-Eclampsia, Pregnancy, Placenta, Humans, Female, Hypoxia-Inducible Factor 1, Hypertension, Pregnancy-Induced, Hypoxia
Abstract: Preeclampsia (PE) is a serious and distinct type of pregnancy-induced hypertension, with an incidence of 2-8% worldwide. PE is defined as pregnancy-related hypertension with proteinuria and peripheral edema after 20 weeks of gestation. Hypoxic placenta triggers the release of inflammatory and humoral substances into maternal circulation, leading to induction of oxidative stress, lipid peroxidation, endothelial dysfunction, and peripheral vasoconstriction. The objective of the present narrative review was to find the association between PE and hypoxia-inducible factor 1 (HIF-1) in pregnant women from a new perspective.HIF-1 is the key transcription factor that regulates cellular responses to hypoxia and low oxygen tension. HIF-1α is involved in the differentiation and growth of the placenta mainly in the first and second trimesters. During normal gestation, HIF-1α responds to the alterations in oxygen tension, cytokine, and angiogenic factors release. HIF-1α is considered a key biomarker of placental function and vascularization during pregnancy. HIF-1α plays a crucial role in the pathogenesis of PE through activation of anti-angiogenic and inhibition of proangiogenic factors. As well, HIF-1α increases the expression of the p38MAPK and NLRP3 inflammasomes, which promote placental inflammation and dysfunction. HIF-1α acts as a potential link between inflammatory signaling pathways and the development of PE.
Published: 2022

10. Society for Cardiovascular Magnetic Resonance 2019 Case of the Week series

Author: Ahmed Heny, John F. Younger, Arushi Dhar, J. Michael Kennen, Vinayak Hedge, Omnia Mohammed, Anmar Kanaa'N, Bryant M. Baldwin, Shane Joseph, Maha Taher, Dominique de Waard, Santokh Dhillon, Madhusudan Ganigara, Yassar Nabeel, Jason N. Johnson, Jafar Alzubi, Christian Hamilton-Craig, Rajiv R. Shah, Ahmed Hamdy, Ahmad Jabri, Aoife Sweeney, Chris Hammet, Joseph A. Lahorra, Nilanjana Misra, Arun Dahiya, Sameh Khalil, Taher Moustafa, Sara Ragab, Ashish Aneja, Christopher Malozzi, Michael V. Cohen, Sylvia S. M. Chen, Maria S. Figarola, Charles Chao, Julia Kar, David Horne, Kurian Pannikottu, Shimaa Abdelrahman Ahmed, V. S. Katikireddi, Allan J. Wesley, Anam Chowdhry, and M. Farhan Nasser
Subjects: Cardiac tumor, medicine.medical_specialty, lcsh:Diseases of the circulatory (Cardiovascular) system, Cardiomyopathy, media_common.quotation_subject, Antineoplastic Agents, Review, Disease, Churg-Strauss Syndrome, 030204 cardiovascular system & hematology, Ventricular Function, Left, 030218 nuclear medicine & medical imaging, Diagnosis, Differential, Heart Neoplasms, Ventricular Dysfunction, Left, Young Adult, 03 medical and health sciences, Presentation, 0302 clinical medicine, Predictive Value of Tests, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Medical physics, Cardiac Tumors, Web site, Angiology, media_common, Radiological and Ultrasound Technology, medicine.diagnostic_test, business.industry, Thrombosis, Magnetic resonance imaging, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Cardiotoxicity, lcsh:RC666-701, Female, Cardiology and Cardiovascular Medicine, business, MRI, Eosinophilic granulomatosis
Abstract: The Society for Cardiovascular Magnetic Resonance (SCMR) is an international society focused on the research, education, and clinical application of cardiovascular magnetic resonance (CMR). The SCMR web site (https://www.scmr.org) hosts a case series designed to present case reports demonstrating the unique attributes of CMR in the diagnosis or management of cardiovascular disease. Each clinical presentation is followed by a brief discussion of the disease and unique role of CMR in disease diagnosis or management guidance. By nature, some of these are somewhat esoteric, but all are instructive. In this publication, we provide a digital archive of the 2019 Case of the Week series as a means of further enhancing the education of those interested in CMR and as a means of more readily identifying these cases using a PubMed or similar search engine.
Published: 2021

11. Association between gynaecological disorders and body mass index in a South African cohort: a retrospective observational study

Author: Celesté van Drünick, Liesl de Waard, Christoffel Joseph Brand Muller, and Gerhard Theron
Subjects: South Africa, Risk Factors, Obstetrics and Gynecology, Humans, Female, Obesity, Overweight, Weight Gain, Body Mass Index, Retrospective Studies
Abstract: A retrospective observational study of new patients who visited the gynaecology outpatient clinic at Tygerberg Hospital, South Africa, between February and June 2019 was conducted to determine the association between body mass index (BMI) and gynaecological disorders. BMI was calculated and analysed concerning the presenting complaint and final diagnosis. From the sample of 651 patients, 18.4% had a normal BMI and 47.3% were classified as overweight or obese class 1. Older age was associated with a higher BMI (
Published: 2022

12. Differential Impact of Coronary Revascularization on Long-Term Clinical Outcome According to Coronary Flow Characteristics:Analysis of the International ILIAS Registry

Author: Rikuta Hamaya, Tim P. van de Hoef, Joo Myung Lee, Masahiro Hoshino, Yoshihisa Kanaji, Tadashi Murai, Coen K.M. Boerhout, Guus A. de Waard, Ji-Hyun Jung, Seung Hun Lee, Hernan Mejia Renteria, Mauro Echavarria-Pinto, Martijn Meuwissen, Hitoshi Matsuo, Maribel Madera-Cambero, Ashkan Eftekhari, Mohamed A. Effat, Koen Marques, Joon-Hyung Doh, Evald H. Christiansen, Rupak Banerjee, Chang-Wook Nam, Giampaolo Niccoli, Masafumi Nakayama, Nobuhiro Tanaka, Eun-Seok Shin, Tetsuo Sasano, Steven A.J. Chamuleau, Paul Knaapen, Javier Escaned, Bon Kwon Koo, Jan J. Piek, Tsunekazu Kakuta, Cardiology, Graduate School, ACS - Heart failure & arrhythmias, ACS - Microcirculation, and ACS - Atherosclerosis & ischemic syndromes
Subjects: Male, coronary flow reserve, percutaneous coronary intervention, Coronary Stenosis, Middle Aged, Coronary Angiography, thermodilution, Fractional Flow Reserve, Myocardial, Treatment Outcome, Predictive Value of Tests, Humans, Female, Registries, Cardiology and Cardiovascular Medicine, fractional flow reserve, coronary artery disease
Abstract: Background: Coronary pressure indices such as fractional flow reserve are the standard for guiding elective revascularization. However, considering additional coronary flow parameters could further individualize and optimize the decision on revascularization. We aimed to investigate the potentially differential prognostic associations of elective percutaneous coronary intervention (PCI) according to coronary flow properties represented by coronary flow reserve (CFR), coronary flow capacity (CFC), and baseline CFC (bCFC). Methods: From the ILIAS Registry (Inclusive Invasive Physiological Assessment in Angina Syndromes) composed of 16 hospitals globally from 7 countries, patients with obstructive coronary artery disease who underwent invasive coronary physiological assessment were included (N=2370 vessels). We assessed effect measure modifications of the association of PCI and 5-year target vessel failure according to CFR, CFC, and bCFC either assessed by Doppler-technique or thermodilution-method. Results: The mean age of the population was 63.3 years, and there were 1322 (73.6%) males. Median fractional flow reserve was 0.85, and PCI was performed in 600 (25.3%) vessels. Reduced CFR, CFC, and abnormal bCFC were defined in 988 (41.7%), 542 (22.9%), and 600 (25.3%) vessels, respectively. Significant effect measure modifications were observed by CFC either in odds ratio ( P =0.0018), additive ( P =0.029), and hazard ratio scale ( P =0.0002). The absolute risk of 5-year target-vessel failure was higher if treated by PCI in vessels with normal CFC by 1.8 (−1.7 to 5.3) percent, while that was lower by −5.9 (−12 to −0.1) percent in those with reduced CFC. CFR and bCFC were not significant effect modifiers in any scales. Similar associations were observed in per-patient analyses, whereas the findings were less robust. Conclusions: We observed qualitative effect measure modification of PCI and 5-year clinical outcomes according to CFC status in additive scale. CFR and bCFC were not robust effect modifiers. Therefore, CFC could be potentially used to optimize the patient selection for elective PCI treatment combined with fractional flow reserve.
Published: 2022
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13. The value of a dedicated multidisciplinary expert panel to assess treatment strategy in patients suffering from colorectal cancer liver metastases

Author: M E de Swart, Geert Kazemier, B.M. Zonderhuis, J J A Joosten, A A van Zweeden, Tessa Hellingman, Martijn R. Meijerink, J W D de Waard, J.J. de Vries, Surgery, General practice, Radiology and nuclear medicine, AGEM - Re-generation and cancer of the digestive system, CCA - Cancer Treatment and quality of life, Internal medicine, and Amsterdam Gastroenterology Endocrinology Metabolism
Subjects: Male, medicine.medical_specialty, Colorectal cancer, Intraclass correlation, 030230 surgery, Tertiary referral hospital, Systemic therapy, 03 medical and health sciences, 0302 clinical medicine, Multidisciplinary approach, Physicians, Humans, Medicine, In patient, Aged, Netherlands, Retrospective Studies, Aged, 80 and over, Patient Care Team, business.industry, General surgery, Liver Neoplasms, Middle Aged, medicine.disease, Inter-rater reliability, Oncology, 030220 oncology & carcinogenesis, Treatment strategy, Female, Interdisciplinary Communication, Surgery, Colorectal Neoplasms, business
Abstract: BACKGROUND: For patients with colorectal cancer liver metastases (CRLM), local treatment is the only treatment with curative intent. The majority of patients with CRLM are however evaluated in multidisciplinary teams of colorectal cancer specialists often lacking expertise in local treatment of liver tumors. The aim of this study was therefore to assess the value of a dedicated multidisciplinary panel consisting of hepatobiliary surgeons and interventional radiologists for patients suffering from liver-only CRLM.METHODS: Patients diagnosed with liver-only CRLM in 2016 were identified in a tertiary referral hospital, and two of the referring hospitals in the Netherlands. Diagnostic imaging was independently reviewed by a panel of four hepatobiliary surgeons and two interventional radiologists to re-evaluate treatment strategy retrospectively. If two or more panelists assessed all lesions eligible for resection and/or ablation, patients were deemed eligible for local treatment with curative intent. Interrater reliability between hepatobiliary surgeons was assessed through intraclass correlation coefficient (ICC) and weighted Cohen's kappa.RESULTS: Diagnostic imaging of 61 patients with liver-only metastases were reviewed. Local treatment strategies appeared feasible in 40/61 (65.6%) patients. Five out of 25 patients (20.0%) initially assigned to systemic therapy were deemed eligible for upfront local treatment with curative intent (p = 0.015). In this subgroup, interrater reliability between hepatobiliary surgeons was substantial (ICC: 0.704, 95% CI: 0.536-0.838, n = 25).CONCLUSION: Assessment of treatment strategy by a dedicated multidisciplinary panel including liver experts may result in an increased number of patients eligible for potentially curative treatment and reduce undertreatment of patients suffering from liver-only CRLM.
Published: 2020
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14. Perinatal fluoxetine exposure disrupts the circadian response to a phase-shifting challenge in female rats

Author: Danielle J. Houwing, Jolien de Waard, Tom Woelders, Jocelien D A Olivier, Sietse F. de Boer, Emma J. Wams, Anouschka S. Ramsteijn, Olivier lab, Beersma lab, and Kas lab
Subjects: Serotonin, endocrine system, medicine.medical_specialty, animal structures, SEROTONIN REUPTAKE INHIBITORS, Serotonin reuptake inhibitor, STRESS-INDUCED HYPERTHERMIA, CLOCK, Hypothermia, Perinatal, Anxiety, MOUSE, Internal medicine, Fluoxetine, Adaptation, Psychological, Animals, Medicine, 5-HT1A receptor, Circadian rhythm, Rats, Wistar, Clock genes, Original Investigation, PRENATAL EXPOSURE, Pharmacology, 8-Hydroxy-2-(di-n-propylamino)tetralin, Perinatal Exposure, Suprachiasmatic nucleus, business.industry, IN-VITRO, SUPRACHIASMATIC NUCLEUS, Antidepressive Agents, Coping style, Circadian Rhythm, Rats, PER2, HIPPOCAMPAL BDNF GENE, 5-HT1A RECEPTORS, Endocrinology, PREGNANCY, nervous system, Circadian behavior, Female, sense organs, Rats, Transgenic, business, Selective Serotonin Reuptake Inhibitors, PER1
Abstract: Rationale Selective serotonin reuptake inhibitor (SSRI) antidepressants are increasingly prescribed during pregnancy. Changes in serotonergic signaling during human fetal development have been associated with changes in brain development and with changes in affective behavior in adulthood. The suprachiasmatic nucleus (SCN) is known to be modulated by serotonin and it is therefore assumed that SSRIs may affect circadian rhythms. However, effects of perinatal SSRI treatment on circadian system functioning in the offspring are largely unknown. Objective Our aim was to investigate the effects of perinatal exposure to the SSRI fluoxetine (FLX) on circadian behavior, affective behavior, and 5-HT1A receptor sensitivity in female rats. In addition, we studied the expression of clock genes and the 5-HT1A receptor in the SCN, as they are potentially involved in underlying mechanisms contributing to changes in circadian rhythms. Results Perinatal FLX exposure shortened the free-running tau in response to the 5-HT1A/7 agonist 8-OH-DPAT. However, FLX exposure did not alter anxiety, stress coping, and 5-HT1A receptor sensitivity. No differences were found in 5-HT1A receptor and clock genes Per1, Per2, Cry1, and Cry2 SCN gene expression. Conclusions Perinatal FLX exposure altered the response to a phase-shifting challenge in female rats, whether this may pose health risks remains to be investigated.
Published: 2020

15. Early Prediction of Intensive Care Unit-Acquired Weakness

Author: Marcus J. Schultz, Juultje Sommers, Janneke Horn, Luuk Wieske, Mengalvio E. Sleeswijk, Camiel Verhamme, Jan Jaap Spijkstra, Esther Witteveen, Monique C. de Waard, Saskia Rijkenberg, Henrik Endeman, Ivo N. van Schaik, Wouter de Ruijter, Neurology, Intensive Care Medicine, Graduate School, Rehabilitation medicine, Amsterdam Neuroscience - Neuroinfection & -inflammation, AMS - Rehabilitation & Development, ACS - Diabetes & metabolism, ACS - Pulmonary hypertension & thrombosis, ACS - Microcirculation, and Intensive care medicine
Subjects: Male, medicine.medical_specialty, Weakness, model validation, Delayed Diagnosis, Critical Care, Icu acquired weakness, Critical Care and Intensive Care Medicine, Model validation, 03 medical and health sciences, 0302 clinical medicine, external validation, Risk Factors, Clinical Decision Rules, Intensive care, Early prediction, medicine, Humans, Prospective Studies, Intensive care medicine, Intensive care unit acquired weakness, Aged, Netherlands, Original Research, Muscle Weakness, business.industry, External validation, 030208 emergency & critical care medicine, prediction, Middle Aged, Reference Standards, Prognosis, Respiration, Artificial, Hospitalization, Impaired consciousness, prediction model, Intensive Care Units, predictors, ROC Curve, 030228 respiratory system, Area Under Curve, Calibration, ICU–acquired weakness, Female, medicine.symptom, business
Abstract: Objectives: An early diagnosis of intensive care unit–acquired weakness (ICU-AW) is often not possible due to impaired consciousness. To avoid a diagnostic delay, we previously developed a prediction model, based on single-center data from 212 patients (development cohort), to predict ICU-AW at 2 days after ICU admission. The objective of this study was to investigate the external validity of the original prediction model in a new, multicenter cohort and, if necessary, to update the model. Methods: Newly admitted ICU patients who were mechanically ventilated at 48 hours after ICU admission were included. Predictors were prospectively recorded, and the outcome ICU-AW was defined by an average Medical Research Council score Results: Of 349 analyzed patients in the validation cohort, 190 (54%) developed ICU-AW. Both model calibration and discrimination of the original model were poor in the validation cohort. The area under the receiver operating characteristics curve (AUC-ROC) was 0.60 (95% confidence interval [CI]: 0.54-0.66). Model updating methods improved calibration but not discrimination. The new prediction model, based on all patients of the development and validation cohort (total of 536 patients) had a fair discrimination, AUC-ROC: 0.70 (95% CI: 0.66-0.75). Conclusions: The previously developed prediction model for ICU-AW showed poor performance in a new independent multicenter validation cohort. Model updating methods improved calibration but not discrimination. The newly derived prediction model showed fair discrimination. This indicates that early prediction of ICU-AW is still challenging and needs further attention.
Published: 2020
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16. Ambulance dispatch calls attributable to influenza A and other common respiratory viruses in the Netherlands (2014‐2016)

Author: Geert Jan Kommer, Liselotte van Asten, Jan van de Kassteele, Paul Engelen, Janneke W. Duijster, Annelies Riezebos-Brilman, Jan de Nooij, Susana Monge, Thomas Krafft, Jens P Valk, Jan de Waard, Wim van der Hoek, RS: CAPHRI - R4 - Health Inequities and Societal Participation, and Metamedica
Subjects: Male, Epidemiology, viruses, respiratory syncytial virus, Ambulances, coronavirus, medicine.disease_cause, Influenza A virus, Medicine, Chromatin structure remodeling (RSC) complex, Child, Respiratory Tract Infections, Coronavirus, Netherlands, education.field_of_study, biology, seasonality, virus diseases, adenovirus, Middle Aged, INTENSIVE-CARE UNITS, Infectious Diseases, rhinovirus, Respiratory virus, Original Article, Female, Seasons, Rhinovirus, influenza, Pulmonary and Respiratory Medicine, Adult, medicine.medical_specialty, SYNDROMIC SURVEILLANCE, Adolescent, Population, Virus, Young Adult, Human metapneumovirus, Influenza, Human, Humans, ambulance, education, Aged, business.industry, Public Health, Environmental and Occupational Health, Emergency Medical Dispatch, Original Articles, biology.organism_classification, infection, Emergency medicine, biology.protein, business
Abstract: Background Ambulance dispatches could be useful for syndromic surveillance of severe respiratory infections. We evaluated whether ambulance dispatch calls of highest urgency reflect the circulation of influenza A virus, influenza B virus, respiratory syncytial virus (RSV), rhinovirus, adenovirus, coronavirus, parainfluenzavirus and human metapneumovirus (hMPV). Methods We analysed calls from four ambulance call centres serving 25% of the population in the Netherlands (2014‐2016). The chief symptom and urgency level is recorded during triage; we restricted our analysis to calls with the highest urgency and identified those compatible with a respiratory syndrome. We modelled the relation between respiratory syndrome calls (RSC) and respiratory virus trends using binomial regression with identity link function. Results We included 211 739 calls, of which 15 385 (7.3%) were RSC. Proportion of RSC showed periodicity with winter peaks and smaller interseasonal increases. Overall, 15% of RSC were attributable to respiratory viruses (20% in out‐of‐office hour calls). There was large variation by age group: in
Published: 2020

17. The effect of scan and patient parameters on the diagnostic performance of AI for detecting coronary stenosis on coronary CT angiography

Author: Rebecca A. Jonas, Emil Barkovich, Andrew D. Choi, William F. Griffin, Joanna Riess, Hugo Marques, Hyuk-Jae Chang, Jung Hyun Choi, Joon-Hyung Doh, Ae-Young Her, Bon-Kwon Koo, Chang-Wook Nam, Hyung-Bok Park, Sang-Hoon Shin, Jason Cole, Alessia Gimelli, Muhammad Akram Khan, Bin Lu, Yang Gao, Faisal Nabi, Ryo Nakazato, U. Joseph Schoepf, Roel S. Driessen, Michiel J. Bom, Randall C. Thompson, James J. Jang, Michael Ridner, Chris Rowan, Erick Avelar, Philippe Généreux, Paul Knaapen, Guus A. de Waard, Gianluca Pontone, Daniele Andreini, Marco Guglielmo, Mouaz H. Al-Mallah, Robert S. Jennings, Tami R. Crabtree, James P. Earls, Cardiology, ACS - Atherosclerosis & ischemic syndromes, ACS - Heart failure & arrhythmias, and NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
Subjects: Male, Artificial intelligence, Computed Tomography Angiography, Coronary Stenosis, CCTA, Atherosclerosis, Coronary artery disease, Coronary computed tomography angiography, Image quality, Settore MED/11 - Malattie dell'Apparato Cardiovascolare, Middle Aged, Coronary Angiography, Predictive Value of Tests, Radiology Nuclear Medicine and imaging, Humans, Female, Radiology, Nuclear Medicine and imaging, Tomography, X-Ray Computed, Aged, Retrospective Studies
Abstract: Publisher Copyright: © 2022 The Authors Objectives: To determine whether coronary computed tomography angiography (CCTA) scanning, scan preparation, contrast, and patient based parameters influence the diagnostic performance of an artificial intelligence (AI) based analysis software for identifying coronary lesions with ≥50% stenosis. Background: CCTA is a noninvasive imaging modality that provides diagnostic and prognostic benefit to patients with coronary artery disease (CAD). The use of AI enabled quantitative CCTA (AI-QCT) analysis software enhances our diagnostic and prognostic ability, however, it is currently unclear whether software performance is influenced by CCTA scanning parameters. Methods: CCTA and quantitative coronary CT (QCT) data from 303 stable patients (64 ± 10 years, 71% male) from the derivation arm of the CREDENCE Trial were retrospectively analyzed using an FDA-cleared cloud-based software that performs AI-enabled coronary segmentation, lumen and vessel wall determination, plaque quantification and characterization, and stenosis determination. The algorithm's diagnostic performance measures (sensitivity, specificity, and accuracy) for detecting coronary lesions of ≥50% stenosis were determined based on concordance with QCA measurements and subsequently compared across scanning parameters (including scanner vendor, model, single vs dual source, tube voltage, dose length product, gating technique, timing method), scan preparation technique (use of beta blocker, use and dose of nitroglycerin), contrast administration parameters (contrast type, infusion rate, iodine concentration, contrast volume) and patient parameters (heart rate and BMI). Results: Within the patient cohort, 13% demonstrated ≥50% stenosis in 3 vessel territories, 21% in 2 vessel territories, 35% in 1 vessel territory while 32% had 400 mg/ml 95.2%; p = 0.0287) in the context of low injection flow rates. On a per patient basis there were no significant differences in AI diagnostic performance measures across all measured scanner, scan technique, patient preparation, contrast, and individual patient parameters. Conclusion: The diagnostic performance of AI-QCT analysis software for detecting moderate to high grade stenosis are unaffected by commonly used CCTA scanning parameters and across a range of common scanning, scanner, contrast and patient variables. Condensed abstract: An AI-enabled quantitative CCTA (AI-QCT) analysis software has been validated as an effective tool for the identification, quantification and characterization of coronary plaque and stenosis through comparison to blinded expert readers and quantitative coronary angiography. However, it is unclear whether CCTA screening parameters related to scanner parameters, scan technique, contrast volume and rate, radiation dose, or a patient's BMI or heart rate at time of scan affect the software's diagnostic measures for detection of moderate to high grade stenosis. AI performance measures were unaffected across a broad range of commonly encountered scanner, patient preparation, scan technique, intravenous contrast and patient parameters. publishersversion published
Published: 2022
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18. Exploring the effect of glaucomatous visual field defects of current drivers on a neuropsychological test battery

Author: Dick de Waard, Nomdo M. Jansonius, Iris Tigchelaar, Markku T. Leinonen, Clinical Neuropsychology, and Perceptual and Cognitive Neuroscience (PCN)
Subjects: Male, medicine.medical_specialty, Automobile Driving, vision, Visual acuity, genetic structures, Trail Making Test, Vision Disorders, Glaucoma, TRAIL, Audiology, Neuropsychological Tests, EYE, Severity of Illness Index, DISEASE, Benton Visual Retention Test, 03 medical and health sciences, 0302 clinical medicine, Percentile rank, AGE, medicine, Memory span, Humans, Cognitive Dysfunction, Aged, medicine.diagnostic_test, business.industry, Montreal Cognitive Assessment, General Medicine, Neuropsychological test, visual field defects, MONTREAL COGNITIVE ASSESSMENT, IMPAIRMENT, PERFORMANCE, medicine.disease, neuropsychological testing, fitness to drive, eye diseases, Ophthalmology, glaucoma, Case-Control Studies, 030221 ophthalmology & optometry, Female, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Purpose This study explores the effect of glaucomatous visual field defects on several neuropsychological tests that are often used in research and in clinical settings. Methods Nineteen glaucoma patients and nineteen healthy participants, which are current drivers and older than 65 years old were included. All participants completed the Montreal Cognitive Assessment (MoCA), the Trail Making Test (TMT), the Benton Visual Retention Test (BVRT), the Snellgrove Maze Task (SMT) and the Digit Span Test (DST). All participants were also tested on contrast sensitivity and near and far visual acuity. For the glaucoma patients, visual field tests were downloaded from hospital servers. Results On the MoCA test, glaucoma patients scored lower than the healthy group, but not significantly. On the MoCA-Blind, the difference was statistically significant. Glaucoma patients also had lower percentile scores on the TMT, with a significant difference in the TMT-A, but this difference largely disappeared in the calculated TMT B-A index, which isolates the cognitive component. The BVRT and SMT showed no significant differences between both groups. In the only non-visual test, the DST, glaucoma patients outperformed the healthy group. Glaucoma severity did not influence results, except for the BVRT on which the moderate/severe group has better scores. Conclusion Using visual items might lead to conclusions about cognition when it should be one about vision. Therefore, careful selection of tests is needed when examining cognition in glaucoma patients.
Published: 2022

19. Relationship between the Clinical Frailty Scale and short-term mortality in patients ≥ 80 years old acutely admitted to the ICU: a prospective cohort study

Author: Fronczek, Jakub, Polok, Kamil, de Lange, Dylan W., Jung, Christian, Beil, Michael, Rhodes, Andrew, Fjølner, Jesper, Górka, Jacek, Andersen, Finn H., Artigas, Antonio, Cecconi, Maurizio, Christensen, Steffen, Joannidis, Michael, Leaver, Susannah, Marsh, Brian, Morandi, Alessandro, Moreno, Rui, Oeyen, Sandra, Agvald-Öhman, Christina, Bollen Pinto, Bernardo, Schefold, Joerg C., Valentin, Andreas, Walther, Sten, Watson, Ximena, Zafeiridis, Tilemachos, Sviri, Sigal, van Heerden, Peter Vernon, Flaatten, Hans, Guidet, Bertrand, Szczeklik, Wojciech, Schmutz, R., Wimmer, F., Eller, P., Joannidis, M., De Buysscher, P., De Neve, N., Oeyen, S., Swinnen, W., Bollen Pinto, B., Abraham, P., Hergafi, L., Schefold, J. C., Biskup, E., Piza, P., Taliadoros, I., Fjølner, J., Dey, N., Sølling, C., Rasmussen, B. S., Christensen, S., Forceville, X., Besch, G., Mentec, H., Michel, P., Mateu, P., Vettoretti, L., Bourenne, J., Marin, N., Guillot, M., Aissaoui, N., Goulenok, C., Thieulot-Rolin, N., Messika, J., Lamhaut, L., Guidet, B., Charron, C., Lauten, A., Sacher, A. L., Brenner, T., Franz, M., Bloos, F., Ebelt, H., Schaller, S. J., Fuest, K., Rabe, C., Dieck, T., Steiner, S., Graf, T., Nia, A. M., Jung, C., Janosi, R. A., Meybohm, P., Simon, P., Utzolino, S., Rahmel, T., Barth, E., Schuster, M., Aidoni, Z., Aloizos, S., Tasioudis, P., Lampiri, K., Zisopoulou, V., Ravani, I., Pagaki, E., Antoniou, A., Katsoulas, T. A., Kounougeri, A., Marinakis, G., Tsimpoukas, F., Spyropoulou, A., Zygoulis, P., Kyparissi, A., Gupta, M., Gurjar, M., Maji, I. M., Hayes, I., Marsh, B., Kelly, Y., Westbrook, A., Fitzpatrick, G., Maheshwari, D., Motherway, C., Negri, G., Spadaro, S., Nattino, G., Pedeferri, M., Boscolo, A., Rossi, S., Calicchio, G., Cubattoli, L., Di Lascio, G., Barbagallo, M., Berruto, F., Codazzi, D., Bottazzi, A., Fumagalli, P., Negro, G., Lupi, G., Savelli, F., Vulcano, G. A., Fumagalli, R., Marudi, A., Lefons, U., Lembo, R., Babini, M., Paggioro, A., Parrini, V., Zaccaria, M., Clementi, S., Gigliuto, C., Facondini, F., Pastorini, S., Munaron, S., Calamai, I., Bocchi, A., Adorni, A., Bocci, M. G., Cortegiani, A., Casalicchio, T., Mellea, S., Graziani, E., Barattini, M., Brizio, E., Rossi, M., Hahn, M., Flaatten, H., Kemmerer, N., Strietzel, H. F., Dybwik, K., Legernaes, T., Klepstad, P., Olaussen, E. B., Olsen, K. I., Brresen, O. M., Bjorsvik, G., Andersen, F. H., Maini, S., Fehrle, L., Czuczwar, M., Krawczyk, P., Ziętkiewicz, M., Nowak, Ł. R., Kotfis, K., Cwyl, K., Gajdosz, R., Biernawska, J., Bohatyrewicz, R., Gawda, R., Grudzień, P., Nasiłowski, P., Popek, N., Cyrankiewicz, W., Wawrzyniak, K., Wnuk, M., Maciejewski, D., Studzińska, D., Żukowski, M., Bernas, S., Piechota, M., Szczeklik, W., Nowak-Kózka, I., Fronczek, J., Serwa, M., Machała, W., Stefaniak, J., Wujtewicz, M., Maciejewski, P., Szymkowiak, M., Adamik, B., Polok, K., Górka, J., Catorze, N., Branco, M. C., Barros, N., Barros, I., Krystopchuk, A., Honrado, T., Sousa, C., Munoz, F., Rebelo, M., Gomes, R., Nunes, J., Dias, C., Fernandes, A. M., Petrisor, C., Constantin, B., Belskiy, V., Boskholov, B., Rodriguez, E., Aguilar, G., Masdeu, G., Jaimes, M. I., Mira, A. P., Bodi, M. A., Mendoza, J. A. B., López-Cuenca, S., Guzman, M. H., Rico-Feijoo, J., Ibarz, M., Alvarez, J. Trenado, Kawati, R., Sivik, J., Nauska, J., Smole, D., Parenmark, F., Lyrén, J., Rockstroh, K., Rydén, S., Spångfors, M., Strinnholm, M., Walther, S., De Geer, L., Nordlund, P., Pålsson, S., Zetterquist, H., Nilsson, A., Thiringer, K., Jungner, M., Bark, B., Nordling, B., Sköld, H., Brorsson, C., Persson, S., Bergström, A., Berkius, J., Holmström, J., van Dijk, I., van Lelyveld-Haas, L. E. M., Jansen, T., Nooteboom, F., van der Voort, P. H. J., de Lange, D., Dieperink, W., de Waard, M. C., de Smet, A. G. E., Bormans, L., Dormans, T., Dempsey, G., Mathew, S. J., Raj, A. S., Grecu, I., Cupitt, J., Lawton, T., Clark, R., Popescu, M., Spittle, N., Faulkner, M., Cowton, A., Williams, P., Elloway, E., Reay, M., Chukkambotla, S., Kumar, R., Al-Subaie, N., Kent, L., Tamm, T., Kajtor, I., Burns, K., Pugh, R., Ostermann, M., Kam, E., Bowyer, H., Smith, N., Templeton, M., Henning, J., Goffin, K., Kapoor, R., Laha, S., Chilton, P., Khaliq, W., Crayford, A., Coetzee, S., Tait, M., Stoker, W., Gimenez, M., Pope, A., Camsooksai, J., Pogson, D., Quigley, K., Ritzema, J., Hormis, A., Boulanger, C., Balasubramaniam, M., Vamplew, L., Burt, K., Martin, D., Craig, J., Prowle, J., Doyle, N., Shelton, J., Scott, C., Donnison, P., Shelton, S., Frey, C., Ryan, C., Spray, D., Barnes, V., Barnes, K., Ridgway, S., Saha, R., Clark, T., Wood, J., Bolger, C., Bassford, C., Lewandowski, J., Zhao, X., Humphreys, S., Dowling, S., Richardson, N., Burtenshaw, A., Stevenson, C., Wilcock, D., Nalapko, Y., Helbok, R., Nollet, J., de Neve, N., Mikačić, M., Bastiansen, A., Husted, A., Dahle, B. E. S., Cramer, C., Ørsnes, D., Thomsen, J. Edelberg, Pedersen, J. J., Enevoldsen, M. Hummelmose, Elkmann, T., Kubisz-Pudelko, A., Collins, A., Hart, C., Randell, G., Filipe, H., Welters, I. D., Evans, J., Lord, J., Jones, J., Ball, J., North, J., Salaunkey, K., De Gordoa, L. Ortiz-Ruiz, Bell, L., Vizcaychipi, M., Mupudzi, M., Lea-Hagerty, M., Spivey, M., Love, N., White, N., Morgan, P., Wakefield, P., Savine, R., Jacob, R., Innes, R., Rose, S., Leaver, S., Mane, T., Ogbeide, V., Baird, Y., Romen, A., Galbois, A., Vinsonneau, C., Thevenin, D., Guerot, E., Savary, G., Chagnon, J. L., Rigaud, J. P., Quenot, J. P., Castaneray, J., Rosman, J., Maizel, J., Tiercelet, K., Hovaere, M. M., Messika, M., Djibré, M., Rolin, N., Burtin, P., Garcon, P., Nseir, S., Valette, X., Horacek, M., Bruno, R. Romano, Allgäuer, S., Dubler, S., Schering, S., Koutsikou, A., Vakalos, A., Raitsiou, B., Flioni, E. N., Neou, E., Papathanakos, G., Koutsodimitropoulos, I., Aikaterini, K., Rovina, N., Kourelea, S., Polychronis, T., Zidianakis, V., Konstantinia, V., Read, C., Martin-Loeches, I., Cracchiolo, A. Neville, Morigi, A., Brusa, S., Elhadi, A., Tarek, A., Khaled, A., Ahmed, H., Belkhair, W. Ali, Cornet, A. D., Gommers, D., van Boven, E., Haringman, J., Haas, L., van den Berg, L., Hoiting, O., de Jager, P., Gerritsen, R. T., Breidablik, A., Slapgard, A., Rime, A. K., Jannestad, B., Sjøbøe, B., Rice, E., Jensen, J. P., Langørgen, J., Tøien, K., Strand, K., Biernacka, A., Kluzik, A., Kudlinski, B., Hymczak, H., Solek-Pastuszka, J., Zorska, J., Krzych, Ł. J., Zukowski, M., Lipińska-Gediga, M., Pietruszko, M., Kozera, N., Sendur, P., Zatorski, P., Galkin, P., Kościuczuk, U., Gola, W., Pinto, A. F., Santos, A. R., Ferreira, I. A., Blanco, J. B., Carvalho, J. T., Maia, J., Candeias, N., Lores, A., Cilloniz, C., Perez-Torres, D., Maseda, E., Prol-Silva, E., Eixarch, G., Gomà, G., Velasco, G. Navarro, Jaimes, M. Irazábal, Villamayor, M. Ibarz, Fernández, N. Llamas, Cubero, P. Jimeno, Tomasa, T., Sjöqvist, A., Schiöler, F., Westberg, H., Thiringer, K. Kleiven, Boroli, F., Eckert, P., Yıldız, I., Yovenko, I., for the VIP1, [missing], VIP2 study group, [missing], Fronczek, Jakub, Polok, Kamil, de Lange, Dylan W, Jung, Christian, Beil, Michael, Rhodes, Andrew, Fjølner, Jesper, Górka, Jacek, Andersen, Finn H, Artigas, Antonio, Cecconi, Maurizio, Christensen, Steffen, Joannidis, Michael, Leaver, Susannah, Marsh, Brian, Morandi, Alessandro, Moreno, Rui, Oeyen, Sandra, Agvald-Öhman, Christina, Bollen Pinto, Bernardo, Schefold, Joerg C, Valentin, Andrea, Walther, Sten, Watson, Ximena, Zafeiridis, Tilemacho, Sviri, Sigal, van Heerden, Peter Vernon, Flaatten, Han, Guidet, Bertrand, Szczeklik, Wojciech, R Schmutz, F Wimmer, P Eller, M Joannidis, P De Buysscher, N De Neve, S Oeyen, W Swinnen, B Bollen Pinto, P Abraham, L Hergafi, J C Schefold, E Biskup, P Piza, I Taliadoros, J Fjølner, N Dey, C Sølling, B S Rasmussen, S Christensen, X Forceville, G Besch, H Mentec, P Michel, P Mateu, P Michel, L Vettoretti, J Bourenne, N Marin, M Guillot, N Aissaoui, C Goulenok, N Thieulot-Rolin, J Messika, L Lamhaut, B Guidet, C Charron, A Lauten, A L Sacher, T Brenner, M Franz, F Bloos, H Ebelt, S J Schaller, K Fuest, C Rabe, T Dieck, S Steiner, T Graf, A M Nia, C Jung, R A Janosi, P Meybohm, P Simon, S Utzolino, T Rahmel, E Barth, C Jung, M Schuster, Z Aidoni, S Aloizos, P Tasioudis, K Lampiri, V Zisopoulou, I Ravani, E Pagaki, A Antoniou, T A Katsoulas, A Kounougeri, G Marinakis, F Tsimpoukas, A Spyropoulou, P Zygoulis, A Kyparissi, M Gupta, M Gurjar, I M Maji, I Hayes, B Marsh, Y Kelly, A Westbrook, G Fitzpatrick, D Maheshwari, C Motherway, G Negri, S Spadaro, G Nattino, M Pedeferri, A Boscolo, S Rossi, G Calicchio, L Cubattoli, G Di Lascio, M Barbagallo, F Berruto, D Codazzi, A Bottazzi, P Fumagalli, G Negro, G Lupi, F Savelli, G A Vulcano, R Fumagalli, A Marudi, U Lefons, R Lembo, M Babini, A Paggioro, V Parrini, M Zaccaria, S Clementi, C Gigliuto, F Facondini, S Pastorini, S Munaron, I Calamai, A Bocchi, A Adorni, M G Bocci, A Cortegiani, T Casalicchio, S Mellea, E Graziani, M Barattini, E Brizio, M Rossi, M Hahn, H Flaatten, N Kemmerer, H F Strietzel, K Dybwik, T Legernaes, P Klepstad, E B Olaussen, K I Olsen, O M Brresen, G Bjorsvik, F H Andersen, S Maini, L Fehrle, M Czuczwar, P Krawczyk, M Ziętkiewicz, Ł R Nowak, K Kotfis, K Cwyl, R Gajdosz, J Biernawska, R Bohatyrewicz, R Gawda, P Grudzień, P Nasiłowski, N Popek, W Cyrankiewicz, K Wawrzyniak, M Wnuk, D Maciejewski, D Studzińska, M Żukowski, S Bernas, M Piechota, W Szczeklik, I Nowak-Kózka, J Fronczek, M Serwa, W Machała, J Stefaniak, M Wujtewicz, P Maciejewski, M Szymkowiak, B Adamik, K Polok, J Górka, N Catorze, M C Branco, N Barros, I Barros, A Krystopchuk, T Honrado, C Sousa, F Munoz, M Rebelo, R Gomes, J Nunes, C Dias, A M Fernandes, C Petrisor, B Constantin, V Belskiy, B Boskholov, E Rodriguez, G Aguilar, G Masdeu, M I Jaimes, A P Mira, M A Bodi, J A B Mendoza, S López-Cuenca, M H Guzman, J Rico-Feijoo, M Ibarz, J Trenado Alvarez, R Kawati, J Sivik, J Nauska, D Smole, F Parenmark, J Lyrén, K Rockstroh, S Rydén, M Spångfors, M Strinnholm, S Walther, L De Geer, P Nordlund, S Pålsson, H Zetterquist, A Nilsson, K Thiringer, M Jungner, B Bark, B Nordling, H Sköld, C Brorsson, S Persson, A Bergström, J Berkius, J Holmström, I van Dijk, L E M van Lelyveld-Haas, T Jansen, F Nooteboom, P H J van der Voort, D de Lange, W Dieperink, M C de Waard, A G E de Smet, L Bormans, T Dormans, G Dempsey, S J Mathew, A S Raj, I Grecu, J Cupitt, T Lawton, R Clark, M Popescu, N Spittle, M Faulkner, A Cowton, P Williams, E Elloway, M Reay, S Chukkambotla, R Kumar, N Al-Subaie, L Kent, T Tamm, I Kajtor, K Burns, R Pugh, M Ostermann, E Kam, H Bowyer, N Smith, M Templeton, J Henning, K Goffin, R Kapoor, S Laha, P Chilton, W Khaliq, A Crayford, S Coetzee, M Tait, W Stoker, M Gimenez, A Pope, J Camsooksai, D Pogson, K Quigley, J Ritzema, A Hormis, C Boulanger, M Balasubramaniam, L Vamplew, K Burt, D Martin, I Grecu, J Craig, J Prowle, N Doyle, J Shelton, C Scott, P Donnison, S Shelton, C Frey, C Ryan, D Spray, C Ryan, V Barnes, K Barnes, S Ridgway, R Saha, L Kent, T Clark, J Wood, C Bolger, C Bassford, A Cowton, J Lewandowski, X Zhao, S Humphreys, S Dowling, N Richardson, A Burtenshaw, C Stevenson, D Wilcock, Y Nalapko, M Joannidis, P Eller, R Helbok, R Schmutz, J Nollet, N de Neve, P De Buysscher, S Oeyen, W Swinnen, M Mikačić, A Bastiansen, A Husted, B E S Dahle, C Cramer, C Sølling, D Ørsnes, J Edelberg Thomsen, J J Pedersen, M Hummelmose Enevoldsen, T Elkmann, A Kubisz-Pudelko, A Pope, A Collins, A S Raj, C Boulanger, C Frey, C Hart, C Bolger, D Spray, G Randell, H Filipe, I D Welters, I Grecu, J Evans, J Cupitt, J Lord, J Henning, J Jones, J Ball, J North, K Salaunkey, L Ortiz-Ruiz De Gordoa, L Bell, M Balasubramaniam, M Vizcaychipi, M Faulkner, M Mupudzi, M Lea-Hagerty, M Reay, M Spivey, N Love, N Spittle, N White, P Williams, P Morgan, P Wakefield, R Savine, R Jacob, R Innes, R Kapoor, S Humphreys, S Rose, S Dowling, S Leaver, T Mane, T Lawton, V Ogbeide, W Khaliq, Y Baird, A Romen, A Galbois, B Guidet, C Vinsonneau, C Charron, D Thevenin, E Guerot, G Besch, G Savary, H Mentec, J L Chagnon, J P Rigaud, J P Quenot, J Castaneray, J Rosman, J Maizel, K Tiercelet, L Vettoretti, M M Hovaere, M Messika, M Djibré, N Rolin, P Burtin, P Garcon, S Nseir, X Valette, C Rabe, E Barth, H Ebelt, K Fuest, M Franz, M Horacek, M Schuster, P Meybohm, R Romano Bruno, S Allgäuer, S Dubler, S J Schaller, S Schering, S Steiner, T Dieck, T Rahmel, T Graf, A Koutsikou, A Vakalos, B Raitsiou, E N Flioni, E Neou, F Tsimpoukas, G Papathanakos, G Marinakis, I Koutsodimitropoulos, K Aikaterini, N Rovina, S Kourelea, T Polychronis, V Zidianakis, V Konstantinia, Z Aidoni, B Marsh, C Motherway, C Read, I Martin-Loeches, A Neville Cracchiolo, A Morigi, I Calamai, S Brusa, A Elhadi, A Tarek, A Khaled, H Ahmed, W Ali Belkhair, A D Cornet, D Gommers, D de Lange, E van Boven, J Haringman, L Haas, L van den Berg, O Hoiting, P de Jager, R T Gerritsen, T Dormans, W Dieperink, A Breidablik, A Slapgard, A K Rime, B Jannestad, B Sjøbøe, E Rice, F H Andersen, H F Strietzel, J P Jensen, J Langørgen, K Tøien, K Strand, M Hahn, P Klepstad, A Biernacka, A Kluzik, B Kudlinski, D Maciejewski, D Studzińska, H Hymczak, J Stefaniak, J Solek-Pastuszka, J Zorska, K Cwyl, Ł J Krzych, M Zukowski, M Lipińska-Gediga, M Pietruszko, M Piechota, M Serwa, M Czuczwar, M Ziętkiewicz, N Kozera, P Nasiłowski, P Sendur, P Zatorski, P Galkin, R Gawda, U Kościuczuk, W Cyrankiewicz, W Gola, A F Pinto, A M Fernandes, A R Santos, C Sousa, I Barros, I A Ferreira, J B Blanco, J T Carvalho, J Maia, N Candeias, N Catorze, V Belskiy, A Lores, A P Mira, C Cilloniz, D Perez-Torres, E Maseda, E Rodriguez, E Prol-Silva, G Eixarch, G Gomà, G Aguilar, G Navarro Velasco, M Irazábal Jaimes, M Ibarz Villamayor, N Llamas Fernández, P Jimeno Cubero, S López-Cuenca, T Tomasa, A Sjöqvist, C Brorsson, F Schiöler, H Westberg, J Nauska, J Sivik, J Berkius, K Kleiven Thiringer, L De Geer, S Walther, F Boroli, J C Schefold, L Hergafi, P Eckert, I Yıldız, I Yovenko, Y Nalapko, R Pugh, and Critical Care
Subjects: Male, Short term mortality, Critical Care and Intensive Care Medicine, Cohort Studies, 0302 clinical medicine, kwetsbaarheid, Medicine and Health Sciences, 80 and over, Medicine, 610 Medicine & health, Prospective cohort study, Correlation of Data, 11 Medical and Health Sciences, Aged, 80 and over, OUTCOMES, Intensive care units, Frailty, VIP1, Aged,&nbsp, Medical emergencies. Critical care. Intensive care. First aid, Scale (social sciences), Female, prospectief onderzoek, Life Sciences & Biomedicine, CRITICALLY-ILL PATIENTS, Study groups, medicine.medical_specialty, Anestesi och intensivvård, 80 jaar en ouder, INTENSIVE-CARE, BED AVAILABILITY, NO, 03 medical and health sciences, Critical Care Medicine, Intensive care, sterfte, General & Internal Medicine, Humans, Aged, Prospective studies, Mortality, In patient, ddc:610, Intensive Care Units, Logistic Models, Prospective Studies, Science & Technology, Anesthesiology and Intensive Care, business.industry, RC86-88.9, Research, 030208 emergency & critical care medicine, ADULTS, Aged, 80 and over, Emergency & Critical Care Medicine, 030228 respiratory system, intensivecareafdelingen, Critical illness, Emergency medicine, VIP2 study group, &nbsp, CRITICAL ILLNESS, business
Abstract: Background The Clinical Frailty Scale (CFS) is frequently used to measure frailty in critically ill adults. There is wide variation in the approach to analysing the relationship between the CFS score and mortality after admission to the ICU. This study aimed to evaluate the influence of modelling approach on the association between the CFS score and short-term mortality and quantify the prognostic value of frailty in this context. Methods We analysed data from two multicentre prospective cohort studies which enrolled intensive care unit patients ≥ 80 years old in 26 countries. The primary outcome was mortality within 30-days from admission to the ICU. Logistic regression models for both ICU and 30-day mortality included the CFS score as either a categorical, continuous or dichotomous variable and were adjusted for patient’s age, sex, reason for admission to the ICU, and admission Sequential Organ Failure Assessment score. Results The median age in the sample of 7487 consecutive patients was 84 years (IQR 81–87). The highest fraction of new prognostic information from frailty in the context of 30-day mortality was observed when the CFS score was treated as either a categorical variable using all original levels of frailty or a nonlinear continuous variable and was equal to 9% using these modelling approaches (p p Conclusion Knowledge about a patient’s frailty status adds a substantial amount of new prognostic information at the moment of admission to the ICU. Arbitrary simplification of the CFS score into fewer groups than originally intended leads to a loss of information and should be avoided. Trial registration NCT03134807 (VIP1), NCT03370692 (VIP2)
Published: 2021
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20. Genome-wide methylation patterns in Marfan syndrome

Author: Mitzi M. van Andel, Maarten Groenink, Maarten P. van den Berg, Janneke Timmermans, Arthur J. H. A. Scholte, Barbara J. M. Mulder, Aeilko H. Zwinderman, Vivian de Waard, Cardiovascular Centre (CVC), Graduate School, Medical Biochemistry, Cardiology, ACS - Heart failure & arrhythmias, APH - Aging & Later Life, APH - Personalized Medicine, Epidemiology and Data Science, APH - Methodology, and ACS - Atherosclerosis & ischemic syndromes
Subjects: Adult, Male, musculoskeletal diseases, congenital, hereditary, and neonatal diseases and abnormalities, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], LOCI, BLOOD-PRESSURE, HEART-DISEASE, Clinical events, All institutes and research themes of the Radboud University Medical Center, Genetics, HISTONE DEACETYLASE 4, Humans, skin and connective tissue diseases, Molecular Biology, DNA METHYLATION, MUTATION, Genetics (clinical), POLYMORPHISMS, GENE-EXPRESSION, EWAS, Methylation loci, RISK, Aortic diameters, Research, ASSOCIATION, Middle Aged, Marfan syndrome, Female, Developmental Biology, Genome-Wide Association Study
Abstract: Background Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the Fibrillin-1 gene (FBN1). Here, we undertook the first epigenome-wide association study (EWAS) in patients with MFS aiming at identifying DNA methylation loci associated with MFS phenotypes that may shed light on the disease process. Methods The Illumina 450 k DNA-methylation array was used on stored peripheral whole-blood samples of 190 patients with MFS originally included in the COMPARE trial. An unbiased genome-wide approach was used, and methylation of CpG-sites across the entire genome was evaluated. Additionally, we investigated CpG-sites across the FBN1-locus (15q21.1) more closely, since this is the gene defective in MFS. Differentially Methylated Positions (DMPs) and Differentially Methylated Regions (DMRs) were identified through regression analysis. Associations between methylation levels and aortic diameters and presence or absence of 21 clinical features of MFS at baseline were analyzed. Moreover, associations between aortic diameter change, and the occurrence of clinical events (death any cause, type-A or -B dissection/rupture, or aortic surgery) and methylation levels were analyzed. Results We identified 28 DMPs that are significantly associated with aortic diameters in patients with MFS. Seven of these DMPs (25%) could be allocated to a gene that was previously associated with cardiovascular diseases (HDAC4, IGF2BP3, CASZ1, SDK1, PCDHGA1, DIO3, PTPRN2). Moreover, we identified seven DMPs that were significantly associated with aortic diameter change and five DMP’s that associated with clinical events. No significant associations at p –8 or p –6 were found with any of the non-cardiovascular phenotypic MFS features. Investigating DMRs, clusters were seen mostly on X- and Y, and chromosome 18–22. The remaining DMRs indicated involvement of a large family of protocadherins on chromosome 5, which were not reported in MFS before. Conclusion This EWAS in patients with MFS has identified a number of methylation loci significantly associated with aortic diameters, aortic dilatation rate and aortic events. Our findings add to the slowly growing literature on the regulation of gene expression in MFS patients.
Published: 2021
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21. The impact of frailty on ICU and 30-day mortality and the level of care in very elderly patients (≥ 80 years)

Author: Flaatten, Hans, De Lange, Dylan W., Morandi, Alessandro, Andersen, Finn H., Artigas, Antonio, Bertolini, Guido, Boumendil, Ariane, Cecconi, Maurizio, Christensen, Steffen, Faraldi, Loredana, Fjølner, Jesper, Jung, Christian, Marsh, Brian, Moreno, Rui, Oeyen, Sandra, Öhman, Christina Agwald, Pinto, Bernardo Bollen, Soliman, Ivo W., Szczeklik, Wojciech, Valentin, Andreas, Watson, Ximena, Zaferidis, Tilemachos, Guidet, Bertrand, Schmutz, René, Wimmer, Franz, Eller, Philipp, Zotter, Klemens, Swinnen, Walter, De Buysscher, Pieter, De Neve, Nikolaas, Abraham, Paul, Fleury, Yvan, Schefold, Joerg C., Biskup, Ewelina, Taliadoros, Ioannis, Piza, Petr, Lauten, Alexander, Sacher, Anna Lena, Brenner, Thorsten, Franz, Marcus, Bloos, Frank, Ebelt, Henning, Schaller, Stefan J., Fuest, Kristina, Rabe, Christian, Dieck, Thorben, Steiner, Stephan, Graf, Tobias, Nia, Amir M., Janosi, Rolf Alexander, Meybohm, Patrick, Simon, Philipp, Utzolino, Stefan, Rahmel, Tim, Barth, Eberhard, Schuster, Michael, Dey, Nilanjan, Sølling, Christoffer, Rasmussen, Bodil Steen, Rodriguez, Enver, Rebollo, Sergio, Aguilar, Gerardo, Masdeu, Gaspar, Jaimes, Marián Irazábal, Prado Mira, Ángela, Bodi, Maria A., Barea Mendoza, Jesus A., López-Cuenca, Sonia, Homez Guzman, Marcela, Rico-Feijoo, Jesús, Ibarz, Mercedes, Trenado-Alvarez, Josep, Forceville, Xavier, Besch, Guillaume, Mentec, Herve, Michel, Philippe, Mateu, Philippe, Vettoretti, Lucie, Bourenne, Jeremy, Marin, Nathalie, Guillot, Max, Aissaoui, Naida, Goulenok, Cyril, Thieulot-Rolin, Nathalie, Messika, Jonathan, Lamhaut, Lionel, Charron, Cyril, Dempsey, Ged, Mathew, Shiju J., Raj, Ashok S., Grecu, Irina, Cupitt, Jason, Lawton, Tom, Clark, Richard, Popescu, Monica, Spittle, Nick, Faulkner, Maria, Cowton, Amanda, Elloway, Esme, Williams, Patricia, Reay, Michael, Chukkambotla, Srikanth, Kumar, Ravi, Al-Subaie, Nawaf, Kent, Linda, Tamm, Tiina, Kajtor, Istvan, Burns, Karen, Pugh, Richard, Ostermann, Marlies, Kam, Elisa, Bowyer, Helen, Smith, Neil, Templeton, Maie, Henning, Jeremy, Goffin, Kelly, Kapoor, Ritoo, Laha, Shondipon, Chilton, Phil, Khaliq, Waqas, Crayford, Alison, Coetzee, Samantha, Tait, Moira, Boultoukas, Evangelos, Stoker, Wendy, Gimenez, Marc, Pope, Alan, Camsooksai, Julie, Pogson, David, Quigley, Kate, Ritzema, Jenny, Hormis, Anil, Boulanger, Carole, Balasubramaniam, M., Vamplew, Luke, Burt, Karen, Martin, Daniel, Craig, Jayne, Prowle, John, Doyle, Nanci, Shelton, Jonathon, Scott, Carmen, Donnison, Phil, Shelton, Sarah, Frey, Christian, Ryan, Christine, Spray, Dominic, Barnes, Veronica, Barnes, Kerry, Furneval, Julie, Ridgway, Stephanie, Saha, Rajnish, Clark, Thomas, Wood, James, Bolger, Clare, Bassford, Christopher, Lewandowski, john, Zhao, Xiaobei, Humphreys, Sally, Dowling, Susan, Richardson, Neil, Burtenshaw, Andrew, Stevenson, Carl, Wilcock, Danielle, Aidoni, Zoi, Aloizos, Stavros, Tasioudis, Polychronis, Lampiri, Kleri, Zisopoulou, Vasiliki, Ifigenia, Ravani, Eymorfia, Pagaki, Angela, Anttoniou, Katsoulas, Theodoros A., Kyparissi, Aikaterini, Aikaterini, Kounougeri, Marinakis, George, Tsimpoukas, Fotios, Spyropoulou, Anastasia, Zygoulis, Paris, Hayes, Ivan, Kelly, Yvelynne, Westbrook, Andrew, Fitzpatrick, Gerry, Maheshwari, Darshana, Motherway, Catherine, Gupta, Manish, Gurjar, Mohan, Maji, Ismail M, Negri, Giovanni, Spadaro, Savino, Nattino, Giuseppe, Pedeferri, Matteo, Boscolo, Annalisa, Rossi, Simona, Rossi, Maurizio, Calicchio, Giuseppe, Cubattoli, Lucia, Di Lascio, Gabriella, Barbagallo, Maria, Berruto, Francesco, Codazzi, Daniela, Bottazzi, Andrea, Fumagalli, Paolo, Negro, Giancarlo, Lupi, Giuseppe, Savelli, Flavia, Vulcano, Giuseppe A., Fumagalli, Roberto, Marudi, Andrea, Lefons, Ugo, Lembo, Rita, Babini, Maria, Paggioro, Alessandra, Parrini, Vieri, Zaccaria, Maria, Clementi, Stefano, Gigliuto, Carmelo, Facondini, Francesca, Pastorini, Simonetta, Munaron, Susanna, Calamai, Italo, Bocchi, Anna, Brizio, Elisabetta, Adorni, Adele, Bocci, Maria Grazia, Cortegiani, Andrea, Casalicchio, Tiziana, Mellea, Serena, Graziani, Elia, Barattini, Massimo, van Dijk, I., van Lelyveld-Haas, L. E. M., Ramnarain, D., Jansen, Tim, Nooteboom, Fleur, van der Voort, Peter H. J., Dieperink, Willem, de Waard, Monique C., Bormans, Laura, Hahn, Michael, Kemmerer, Nicolai, Strietzel, Hans Frank, Fehrle, Lutz, Dybwik, Knut, Legernaes, Terje, Klepstad, Pål, Olaussen, Even Braut, Olsen, Knut Inge, Børresen, Ole Marius, Bjørsvik, Geir, Maini, Sameer, Czuczwar, Miroslaw, Krawczyk, Pawel, Ziętkiewicz, Mirosław, Nowak, Łukasz R., Kotfis, Katarzyna, Cwyl, Katarzyna, Gajdosz, Ryszard, Biernawska, Jowita, Grudzień, Paweł, Nasiłowski, Paweł, Popek, Natalia, Cyrankiewicz, Waldemar, Wnuk, Marek, Maciejewski, Dariusz, Studzińska, Dorota, Zukowski, Maciej, Bernas, Szymon, Serwa, Marta, Stefaniak, Jan, Pawel, Maciejewski, Szymkowiak, Malgorzata, Adamik, Barbara, Catorze, Nuno, Castelo Branco, Miguel, Barros, Inês, Barros, Nelson, Krystopchuk, Andriy, Honrado, Teresa, Sousa, Cristina, Munoz, Francisco, Rebelo, Marta, Gomes, Rui, Nunes, Jorge, Dias, Celeste, Fernandes, Ana Margarida, Petrisor, Cristina, Constantin, Bodolea, Belskiy, Vladislav, Boskholov, Boris, Kawati, Rafael, Sivik, Joakim, Nauska, Jessica, Smole, Daniel, Parenmark, Fredric, Lyrén, Johanna, Rockstroh, Katalin, Rydén, Sara, Spångfors, Martin, Strinnholm, Morten, Walther, Sten, De Geer, Lina, Nordlund, Peter, Pålsson, Staffan, Zetterquist, Harald, Nilsson, Annika, Thiringer, Karin, Jungner, Mårten, Bark, Björn, Nordling, Berit, Sköld, Hans, Brorsson, Camilla, Persson, Stefan, Bergström, Anna, Berkius, Johan, Holmström, Johanna, Yapici, Nihan, University of Bergen (UiB), Haukeland University Hospital, University Medical Center [Utrecht], CIBER de Epidemiología y Salud Pública (CIBERESP), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), St George’s University Hospitals, Aarhus University Hospital, Mater Misericordiae University Hospital (The Mater Hospital), NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Ghent University Hospital, Karolinska University Hospital [Stockholm], Hôpitaux Universitaires de Genève (HUG), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, Flaatten, H, De Lange, D, Morandi, A, Andersen, F, Artigas, A, Bertolini, G, Boumendil, A, Cecconi, M, Christensen, S, Faraldi, L, Fjolner, J, Jung, C, Marsh, B, Moreno, R, Oeyen, S, Ohman, C, Pinto, B, Soliman, I, Szczeklik, W, Valentin, A, Watson, X, Zaferidis, T, Guidet, B, Schmutz, R, Wimmer, F, Eller, P, Zotter, K, Swinnen, W, De Buysscher, P, De Neve, N, Abraham, P, Fleury, Y, Schefold, J, Biskup, E, Taliadoros, I, Piza, P, Lauten, A, Sacher, A, Brenner, T, Franz, M, Bloos, F, Ebelt, H, Schaller, S, Fuest, K, Rabe, C, Dieck, T, Steiner, S, Graf, T, Nia, A, Janosi, R, Meybohm, P, Simon, P, Utzolino, S, Rahmel, T, Barth, E, Schuster, M, Dey, N, Solling, C, Rasmussen, B, Rodriguez, E, Rebollo, S, Aguilar, G, Masdeu, G, Jaimes, M, Prado Mira, A, Bodi, M, Barea Mendoza, J, Lopez-Cuenca, S, Homez Guzman, M, Rico-Feijoo, J, Ibarz, M, Trenado-Alvarez, J, Forceville, X, Besch, G, Mentec, H, Michel, P, Mateu, P, Vettoretti, L, Bourenne, J, Marin, N, Guillot, M, Aissaoui, N, Goulenok, C, Thieulot-Rolin, N, Messika, J, Lamhaut, L, Charron, C, Dempsey, G, Mathew, S, Raj, A, Grecu, I, Cupitt, J, Lawton, T, Clark, R, Popescu, M, Spittle, N, Faulkner, M, Cowton, A, Elloway, E, Williams, P, Reay, M, Chukkambotla, S, Kumar, R, Al-Subaie, N, Kent, L, Tamm, T, Kajtor, I, Burns, K, Pugh, R, Ostermann, M, Kam, E, Bowyer, H, Smith, N, Templeton, M, Henning, J, Goffin, K, Kapoor, R, Laha, S, Chilton, P, Khaliq, W, Crayford, A, Coetzee, S, Tait, M, Boultoukas, E, Stoker, W, Gimenez, M, Pope, A, Camsooksai, J, Pogson, D, Quigley, K, Ritzema, J, Hormis, A, Boulanger, C, Balasubramaniam, M, Vamplew, L, Burt, K, Martin, D, Craig, J, Prowle, J, Doyle, N, Shelton, J, Scott, C, Donnison, P, Shelton, S, Frey, C, Ryan, C, Spray, D, Barnes, V, Barnes, K, Furneval, J, Ridgway, S, Saha, R, Clark, T, Wood, J, Bolger, C, Bassford, C, Lewandowski, J, Zhao, X, Humphreys, S, Dowling, S, Richardson, N, Burtenshaw, A, Stevenson, C, Wilcock, D, Aidoni, Z, Aloizos, S, Tasioudis, P, Lampiri, K, Zisopoulou, V, Ifigenia, R, Eymorfia, P, Angela, A, Katsoulas, T, Kyparissi, A, Aikaterini, K, Marinakis, G, Tsimpoukas, F, Spyropoulou, A, Zygoulis, P, Hayes, I, Kelly, Y, Westbrook, A, Fitzpatrick, G, Maheshwari, D, Motherway, C, Gupta, M, Gurjar, M, Maji, I, Negri, G, Spadaro, S, Nattino, G, Pedeferri, M, Boscolo, A, Rossi, S, Rossi, M, Calicchio, G, Cubattoli, L, Di Lascio, G, Barbagallo, M, Berruto, F, Codazzi, D, Bottazzi, A, Fumagalli, P, Negro, G, Lupi, G, Savelli, F, Vulcano, G, Fumagalli, R, Marudi, A, Lefons, U, Lembo, R, Babini, M, Paggioro, A, Parrini, V, Zaccaria, M, Clementi, S, Gigliuto, C, Facondini, F, Pastorini, S, Munaron, S, Calamai, I, Bocchi, A, Brizio, E, Adorni, A, Bocci, M, Cortegiani, A, Casalicchio, T, Mellea, S, Graziani, E, Barattini, M, van Dijk, I, van Lelyveld-Haas, L, Ramnarain, D, Jansen, T, Nooteboom, F, van der Voort, P, Dieperink, W, de Waard, M, Bormans, L, Hahn, M, Kemmerer, N, Strietzel, H, Fehrle, L, Dybwik, K, Legernaes, T, Klepstad, P, Olaussen, E, Olsen, K, Borresen, O, Bjorsvik, G, Maini, S, Czuczwar, M, Krawczyk, P, Zietkiewicz, M, Nowak, L, Kotfis, K, Cwyl, K, Gajdosz, R, Biernawska, J, Grudzien, P, Nasilowski, P, Popek, N, Cyrankiewicz, W, Wnuk, M, Maciejewski, D, Studzinska, D, Zukowski, M, Bernas, S, Serwa, M, Stefaniak, J, Pawel, M, Szymkowiak, M, Adamik, B, Catorze, N, Castelo Branco, M, Barros, I, Barros, N, Krystopchuk, A, Honrado, T, Sousa, C, Munoz, F, Rebelo, M, Gomes, R, Nunes, J, Dias, C, Fernandes, A, Petrisor, C, Constantin, B, Belskiy, V, Boskholov, B, Kawati, R, Sivik, J, Nauska, J, Smole, D, Parenmark, F, Lyren, J, Rockstroh, K, Ryden, S, Spangfors, M, Strinnholm, M, Walther, S, De Geer, L, Nordlund, P, Palsson, S, Zetterquist, H, Nilsson, A, Thiringer, K, Jungner, M, Bark, B, Nordling, B, Skold, H, Brorsson, C, Persson, S, Bergstrom, A, Berkius, J, Holmstrom, J, Yapici, N, Flaatten, Han, De Lange, Dylan W., Morandi, Alessandro, Andersen, Finn H., Artigas, Antonio, Bertolini, Guido, Boumendil, Ariane, Cecconi, Maurizio, Christensen, Steffen, Faraldi, Loredana, Fjølner, Jesper, Jung, Christian, Marsh, Brian, Moreno, Rui, Oeyen, Sandra, Öhman, Christina Agwald, Pinto, Bernardo Bollen, Soliman, Ivo W., Szczeklik, Wojciech, Valentin, Andrea, Watson, Ximena, Zaferidis, Tilemacho, Guidet, Bertrand, Schmutz, René, Wimmer, Franz, Eller, Philipp, Zotter, Klemen, Swinnen, Walter, De Buysscher, Pieter, De Neve, Nikolaa, Abraham, Paul, Fleury, Yvan, Schefold, Joerg C., Biskup, Ewelina, Taliadoros, Ioanni, Piza, Petr, Lauten, Alexander, Sacher, Anna Lena, Brenner, Thorsten, Franz, Marcu, Bloos, Frank, Ebelt, Henning, Schaller, Stefan J., Fuest, Kristina, Rabe, Christian, Dieck, Thorben, Steiner, Stephan, Graf, Tobia, Nia, Amir M., Janosi, Rolf Alexander, Meybohm, Patrick, Simon, Philipp, Utzolino, Stefan, Rahmel, Tim, Barth, Eberhard, Schuster, Michael, Dey, Nilanjan, Sølling, Christoffer, Rasmussen, Bodil Steen, Rodriguez, Enver, Rebollo, Sergio, Aguilar, Gerardo, Masdeu, Gaspar, Jaimes, Marián Irazábal, Prado Mira, Ángela, Bodi, Maria A., Barea Mendoza, Jesus A., López-Cuenca, Sonia, Homez Guzman, Marcela, Rico-Feijoo, Jesú, Ibarz, Mercede, Trenado-Alvarez, Josep, Forceville, Xavier, Besch, Guillaume, Mentec, Herve, Michel, Philippe, Mateu, Philippe, Vettoretti, Lucie, Bourenne, Jeremy, Marin, Nathalie, Guillot, Max, Aissaoui, Naida, Goulenok, Cyril, Thieulot-Rolin, Nathalie, Messika, Jonathan, Lamhaut, Lionel, Charron, Cyril, Dempsey, Ged, Mathew, Shiju J., Raj, Ashok S., Grecu, Irina, Cupitt, Jason, Lawton, Tom, Clark, Richard, Popescu, Monica, Spittle, Nick, Faulkner, Maria, Cowton, Amanda, Elloway, Esme, Williams, Patricia, Reay, Michael, Chukkambotla, Srikanth, Kumar, Ravi, Al-Subaie, Nawaf, Kent, Linda, Tamm, Tiina, Kajtor, Istvan, Burns, Karen, Pugh, Richard, Ostermann, Marlie, Kam, Elisa, Bowyer, Helen, Smith, Neil, Templeton, Maie, Henning, Jeremy, Goffin, Kelly, Kapoor, Ritoo, Laha, Shondipon, Chilton, Phil, Khaliq, Waqa, Crayford, Alison, Coetzee, Samantha, Tait, Moira, Boultoukas, Evangelo, Stoker, Wendy, Gimenez, Marc, Pope, Alan, Camsooksai, Julie, Pogson, David, Quigley, Kate, Ritzema, Jenny, Hormis, Anil, Boulanger, Carole, Balasubramaniam, M., Vamplew, Luke, Burt, Karen, Martin, Daniel, Craig, Jayne, Prowle, John, Doyle, Nanci, Shelton, Jonathon, Scott, Carmen, Donnison, Phil, Shelton, Sarah, Frey, Christian, Ryan, Christine, Spray, Dominic, Barnes, Veronica, Barnes, Kerry, Furneval, Julie, Ridgway, Stephanie, Saha, Rajnish, Clark, Thoma, Wood, Jame, Bolger, Clare, Bassford, Christopher, Lewandowski, john, Zhao, Xiaobei, Humphreys, Sally, Dowling, Susan, Richardson, Neil, Burtenshaw, Andrew, Stevenson, Carl, Wilcock, Danielle, Aidoni, Zoi, Aloizos, Stavro, Tasioudis, Polychroni, Lampiri, Kleri, Zisopoulou, Vasiliki, Ifigenia, Ravani, Eymorfia, Pagaki, Angela, Anttoniou, Katsoulas, Theodoros A., Kyparissi, Aikaterini, Aikaterini, Kounougeri, Marinakis, George, Tsimpoukas, Fotio, Spyropoulou, Anastasia, Zygoulis, Pari, Hayes, Ivan, Kelly, Yvelynne, Westbrook, Andrew, Fitzpatrick, Gerry, Maheshwari, Darshana, Motherway, Catherine, Gupta, Manish, Gurjar, Mohan, Maji, Ismail M, Negri, Giovanni, Spadaro, Savino, Nattino, Giuseppe, Pedeferri, Matteo, Boscolo, Annalisa, Rossi, Simona, Rossi, Maurizio, Calicchio, Giuseppe, Cubattoli, Lucia, Di Lascio, Gabriella, Barbagallo, Maria, Berruto, Francesco, Codazzi, Daniela, Bottazzi, Andrea, Fumagalli, Paolo, Negro, Giancarlo, Lupi, Giuseppe, Savelli, Flavia, Vulcano, Giuseppe A., Fumagalli, Roberto, Marudi, Andrea, Lefons, Ugo, Lembo, Rita, Babini, Maria, Paggioro, Alessandra, Parrini, Vieri, Zaccaria, Maria, Clementi, Stefano, Gigliuto, Carmelo, Facondini, Francesca, Pastorini, Simonetta, Munaron, Susanna, Calamai, Italo, Bocchi, Anna, Brizio, Elisabetta, Adorni, Adele, Bocci, Maria Grazia, Cortegiani, Andrea, Casalicchio, Tiziana, Mellea, Serena, Graziani, Elia, Barattini, Massimo, van Dijk, I., van Lelyveld-Haas, L.E.M., Ramnarain, D., Jansen, Tim, Nooteboom, Fleur, van der Voort, Peter H.J., Dieperink, Willem, de Waard, Monique C., Bormans, Laura, Hahn, Michael, Kemmerer, Nicolai, Strietzel, Hans Frank, Fehrle, Lutz, Dybwik, Knut, Legernaes, Terje, Klepstad, Pål, Olaussen, Even Braut, Olsen, Knut Inge, Børresen, Ole Mariu, Bjørsvik, Geir, Maini, Sameer, Czuczwar, Miroslaw, Krawczyk, Pawel, Ziętkiewicz, Mirosław, Nowak, Łukasz R., Kotfis, Katarzyna, Cwyl, Katarzyna, Gajdosz, Ryszard, Biernawska, Jowita, Grudzień, Paweł, Nasiłowski, Paweł, Popek, Natalia, Cyrankiewicz, Waldemar, Wnuk, Marek, Maciejewski, Dariusz, Studzińska, Dorota, Zukowski, Maciej, Bernas, Szymon, Serwa, Marta, Stefaniak, Jan, Pawel, Maciejewski, Szymkowiak, Malgorzata, Adamik, Barbara, Catorze, Nuno, Castelo Branco, Miguel, Barros, Inê, Barros, Nelson, Krystopchuk, Andriy, Honrado, Teresa, Sousa, Cristina, Munoz, Francisco, Rebelo, Marta, Gomes, Rui, Nunes, Jorge, Dias, Celeste, Fernandes, Ana Margarida, Petrisor, Cristina, Constantin, Bodolea, Belskiy, Vladislav, Boskholov, Bori, Kawati, Rafael, Sivik, Joakim, Nauska, Jessica, Smole, Daniel, Parenmark, Fredric, Lyrén, Johanna, Rockstroh, Katalin, Rydén, Sara, Spångfors, Martin, Strinnholm, Morten, Walther, Sten, De Geer, Lina, Nordlund, Peter, Pålsson, Staffan, Zetterquist, Harald, Nilsson, Annika, Thiringer, Karin, Jungner, Mårten, Bark, Björn, Nordling, Berit, Sköld, Han, Brorsson, Camilla, Persson, Stefan, Bergström, Anna, Berkius, Johan, Holmström, Johanna, and Yapici, Nihan
Subjects: Male, Time Factors, Outcome Assessment, Frail Elderly/statistics & numerical data, [SDV]Life Sciences [q-bio], HSJ UCI, Passive, Critical Care and Intensive Care Medicine, Frailty/classification/diagnosis/mortality/therapy, Severity of Illness Index, Severity of illne, Elderly, 0302 clinical medicine, Quality of life, Frailty, ICU, Mortality, Octogenarians, Severity of illness, Aged, 80 and over, Critical Illness, Europe, Euthanasia, Passive, Female, Frail Elderly, Geriatric Assessment, Humans, Intensive Care Units, Length of Stay, Outcome Assessment, Health Care, Proportional Hazards Models, Prospective Studies, Quality of Life, Hospital Mortality, 80 and over, 030212 general & internal medicine, Prospective cohort study, education.field_of_study, ddc:617, Mortality rate, [SDV] Life Sciences [q-bio], Length of Stay/statistics & numerical data, Cohort, Intensive Care Units/statistics & numerical data, Critical Illne, SOFA score, Human, medicine.medical_specialty, Time Factor, Intensive Care Unit, Population, INTENSIVE-CARE, Europe/epidemiology, Outcome Assessment (Health Care), 03 medical and health sciences, Octogenarian, Intensive care, Journal Article, medicine, COHORT, Octogenarinans, Intensive care medicine, education, Aged, OLDER, Euthanasia, business.industry, 030208 emergency & critical care medicine, Health Care, Prospective Studie, Critical Illness/mortality, UNIT, Emergency medicine, Proportional Hazards Model, business
Abstract: Purpose: Very old critical ill patients are a rapid expanding group in the ICU. Indications for admission, triage criteria and level of care are frequently discussed for such patients. However, most relevant outcome studies in this group frequently find an increased mortality and a reduced quality of life in survivors. The main objective was to study the impact of frailty compared with other variables with regards to short-term outcome in the very old ICU population. Methods: A transnational prospective cohort study from October 2016 to May 2017 with 30days follow-up was set up by the European Society of Intensive Care Medicine. In total 311 ICUs from 21 European countries participated. The ICUs included the first consecutive 20 very old (≥80years) patients admitted to the ICU within a 3-month inclusion period. Frailty, SOFA score and therapeutic procedures were registered, in addition to limitations of care. For measurement of frailty the Clinical Frailty Scale was used at ICU admission. The main outcomes were ICU and 30-day mortality and survival at 30days. Results: A total of 5021 patients with a median age of 84years (IQR 81–86years) were included in the final analysis, 2404 (47.9%) were women. Admission was classified as acute in 4215 (83.9%) of the patients. Overall ICU and 30-day mortality rates were 22.1% and 32.6%. During ICU stay 23.8% of the patients did not receive specific ICU procedures: ventilation, vasoactive drugs or renal replacement therapy. Frailty (values ≥5) was found in 43.1% and was independently related to 30-day survival (HR 1.54; 95% CI 1.38–1.73) for frail versus non-frail. Conclusions: Among very old patients (≥80years) admitted to the ICU, the consecutive classes in Clinical Frailty Scale were inversely associated with short-term survival. The scale had a very low number of missing data. These findings provide support to add frailty to the clinical assessment in this patient group. Trial registration: ClinicalTrials.gov (ID: NCT03134807).
Published: 2017
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22. Cumulative Prognostic Score Predicting Mortality in Patients Older Than 80 Years Admitted to the ICU

Author: de Lange D. W., Brinkman S., Flaatten H., Boumendil A., Morandi A., Andersen F. H., Artigas A., Bertolini G., Cecconi M., Christensen S., Faraldi L., Fjolner J., Jung C., Marsh B., Moreno R., Oeyen S., Ohman C. A., Bollen Pinto B., de Smet A. M. G. A., Soliman I. W., Szczeklik W., Valentin A., Watson X., Zafeiridis T., Guidet B., Schmutz R., Wimmer F., Eller P., Joannidis M., De Buysscher P., De Neve N., Swinnen W., Abraham P., Hergafi L., Schefold Joerg. C., Biskup E., Piza P., Taliadoros I., Dey N., Solling C., Rasmussen B. S., Forceville X., Besch G., Mentec H., Michel P., Mateu P., Vettoretti L., Bourenne J., Marin N., Guillot M., Aissaoui N., Goulenok C., Thieulot-Rolin N., Messika J., Lamhaut L., Charron C., Lauten A., Sacher A. L., Brenner T., Franz M., Bloos F., Ebelt H., Schaller S. J., Fuest Kristina., Rabe C., Dieck T., Steiner S., Graf T., Nia A. M., Janosi R. A., Meybohm P., Simon P., Utzolino S., Rahmel T., Barth E., Schuster M., Aidoni Z., Aloizos S., Tasioudis P., Lampiri K., Zisopoulou V., Ravani I., Pagaki E., Antoniou A., Katsoulas T. A., Kounougeri A., Marinakis G., Tsimpoukas F., Spyropoulou A., Zygoulis P., Kyparissi A., Gupta M., Gurjar M., Maji I. M., Hayes I., Kelly Y., Westbrook A., Fitzpatrick G., Maheshwari D., Motherway C., Negri G., Spadaro S., Nattino G., Pedeferri M., Boscolo A., Rossi S., Calicchio G., Cubattoli L., Di Lascio G., Barbagallo M., Berruto F., Codazzi D., Bottazzi A., Fumagalli P., Negro G., Lupi G., Savelli F., Vulcano Giuseppe. A., Fumagalli R., Marudi A., Lefons U., Lembo R., Babini M., Paggioro A., Parrini V., Zaccaria M., Clementi S., Gigliuto C., Facondini F., Pastorini S., Munaron S., Calamai I., Bocchi A., Adorni A., Bocci M. G., Cortegiani A., Casalicchio T., Mellea S., Graziani E., Barattini M., Brizio E., Rossi M., Hahn M., Kemmerer N., Strietzel H. F., Dybwik K., Legernaes T., Klepstad P., Olaussen E. B., Olsen K. I., Brresen O. M., Bjorsvik G., Maini S., Fehrle L., Czuczwar M., Krawczyk P., Zietkiewicz M., Nowak L. R., Kotfis K., Cwyl K., Gajdosz R., Biernawska J., Bohatyrewicz Romuald., Gawda R., Grudzien P., Nasilowski P., Popek N., Cyrankiewicz W., Wawrzyniak K., Wnuk M., Maciejewski D., Studzinska D., Zukowski M., Bernas S., Piechota M., Nowak I., Fronczek J., Serwa M., Machala W., Stefaniak J., Wujtewicz M., Maciejewski P., Szymkowiak M., Adamik B., Catorze N., Branco M. C., Barros I., Barros N., Krystopchuk A., Honrado T., Sousa C., Munoz F., Rebelo M., Gomes R., Nunes J., Dias Celeste., Fernandes A. M., Petrisor C., Constantin B., Belskiy V., Boskholov B., Rodriguez E., Rebollo S., Aguilar G., Masdeu G., Jaimes M. I., Mira A. P., Bodi Maria. A., Mendoza J. A. B., Cuenca S. L., Guzman M. H., Rico-Feijoo J., Ibarz M., Alvarez J. T., Kawati R., Sivik J., Nauska J., Smole D., Parenmark F., Lyren J., Rockstroh K., Ryden S., Strinnholm M., Walther S., De Geer L., Nordlund P., Palsson S., Zetterquist H., Nilsson A., Thiringer K., Jungner M., Bark B., Nordling B., Skold H., Brorsson C., Persson S., Bergstrom A., Berkius J., Holmstrom J., van Dijk I., van Lelyveld-Haas L. E. M., Ramnarain D., Jansen T., Nooteboom F., van der Voort P. H. J., Dieperink W., de Waard M. C., Bormans L., Dormans Tom., Dempsey G., Mathew S. J., Raj A. S., Grecu I., Cupitt J., Lawton T., Clark R., Popescu M., Spittle N., Faulkner M., Cowton A., Elloway E., Williams P., Reay M., Chukkambotla S., Kumar R., Al-Subaie N., Kent L., Tamm T., Kajtor I., Burns K., Pugh R., Ostermann M., Kam E., Bowyer H., Smith N., Templeton M., Henning J., Goffin K., Kapoor R., Laha S., Chilton P., Khaliq W., Crayford A., Coetzee S., Tait M., Stoker W., Gimenez M., Pope A., Camsooksai J., Pogson D., Quigley K., Ritzema J., Hormis A., Boulanger C., Balasubramaniam M., Vamplew L., Burt K., Martin D., Craig J., Prowle J., Doyle N., Shelton J., Scott Carmen., Donnison P., Shelton S., Frey C., Ryan C., Spray D., Barnes V., Barnes K., Ridgway S., Saha R., Clark T., Wood J., Bolger C., Bassford C., Lewandowski J., Zhao X., Humphreys S., Dowling S., Richardson N., Burtenshaw A., Stevenson C., Wilcock D., Nalapko Y., Microbes in Health and Disease (MHD), Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Medical Informatics, APH - Methodology, APH - Quality of Care, de Lange, D, Brinkman, S, Flaatten, H, Boumendil, A, Morandi, A, Andersen, F, Artigas, A, Bertolini, G, Cecconi, M, Christensen, S, Faraldi, L, Fjolner, J, Jung, C, Marsh, B, Favarato, M, Oeyen, S, Ohman, C, Bollen Pinto, B, de Smet, A, Soliman, I, Szczeklik, W, Valentin, A, Watson, X, Zafeiridis, T, Guidet, B, Schmutz, R, Wimmer, F, Eller, P, Joannidis, M, De Buysscher, P, De Neve, N, Swinnen, W, Abraham, P, Hergafi, L, Schefold, J, Biskup, E, Piza, P, Taliadoros, I, Dey, N, Solling, C, Rasmussen, B, Forceville, X, Besch, G, Mentec, H, Michel, P, Mateu, P, Vettoretti, L, Bourenne, J, Marin, N, Guillot, M, Aissaoui, N, Goulenok, C, Thieulot-Rolin, N, Messika, J, Lamhaut, L, Charron, C, Lauten, A, Sacher, A, Brenner, T, Franz, M, Bloos, F, Ebelt, H, Schaller, S, Fuest, K, Rabe, C, Dieck, T, Steiner, S, Graf, T, Nia, A, Janosi, R, Meybohm, P, Simon, P, Utzolino, S, Rahmel, T, Barth, E, Schuster, M, Aidoni, Z, Aloizos, S, Tasioudis, P, Lampiri, K, Zisopoulou, V, Ravani, I, Pagaki, E, Antoniou, A, Katsoulas, T, Kounougeri, A, Marinakis, G, Tsimpoukas, F, Spyropoulou, A, Zygoulis, P, Kyparissi, A, Gupta, M, Gurjar, M, Maji, I, Hayes, I, Kelly, Y, Westbrook, A, Fitzpatrick, G, Maheshwari, D, Motherway, C, Negri, G, Spadaro, S, Nattino, G, Pedeferri, M, Boscolo, A, Rossi, S, Calicchio, G, Cubattoli, L, Di Lascio, G, Barbagallo, M, Berruto, F, Codazzi, D, Bottazzi, A, Fumagalli, P, Negro, G, Lupi, G, Savelli, F, Vulcano, G, Fumagalli, R, Marudi, A, Lefons, U, Lembo, R, Babini, M, Paggioro, A, Parrini, V, Zaccaria, M, Clementi, S, Gigliuto, C, Facondini, F, Pastorini, S, Munaron, S, Calamai, I, Bocchi, A, Adorni, A, Bocci, M, Cortegiani, A, Casalicchio, T, Mellea, S, Graziani, E, Barattini, M, Brizio, E, Rossi, M, Hahn, M, Kemmerer, N, Strietzel, H, Dybwik, K, Legernaes, T, Klepstad, P, Olaussen, E, Olsen, K, Brresen, O, Bjorsvik, G, Maini, S, Fehrle, L, Czuczwar, M, Krawczyk, P, Zietkiewicz, M, Nowak, L, Kotfis, K, Cwyl, K, Gajdosz, R, Biernawska, J, Bohatyrewicz, R, Gawda, R, Grudzien, P, Nasilowski, P, Popek, N, Cyrankiewicz, W, Wawrzyniak, K, Wnuk, M, Maciejewski, D, Studzinska, D, Zukowski, M, Bernas, S, Piechota, M, Nowak, I, Fronczek, J, Serwa, M, Machala, W, Stefaniak, J, Wujtewicz, M, Maciejewski, P, Szymkowiak, M, Adamik, B, Catorze, N, Branco, M, Barros, I, Barros, N, Krystopchuk, A, Honrado, T, Sousa, C, Munoz, F, Rebelo, M, Gomes, R, Nunes, J, Dias, C, Fernandes, A, Petrisor, C, Constantin, B, Belskiy, V, Boskholov, B, Rodriguez, E, Rebollo, S, Aguilar, G, Masdeu, G, Jaimes, M, Mira, A, Bodi, M, Mendoza, J, Cuenca, S, Guzman, M, Rico-Feijoo, J, Ibarz, M, Alvarez, J, Kawati, R, Sivik, J, Nauska, J, Smole, D, Parenmark, F, Lyren, J, Rockstroh, K, Ryden, S, Strinnholm, M, Walther, S, De Geer, L, Nordlund, P, Palsson, S, Zetterquist, H, Nilsson, A, Thiringer, K, Jungner, M, Bark, B, Nordling, B, Skold, H, Brorsson, C, Persson, S, Bergstrom, A, Berkius, J, Holmstrom, J, van Dijk, I, van Lelyveld-Haas, L, Ramnarain, D, Jansen, T, Nooteboom, F, van der Voort, P, Dieperink, W, de Waard, M, Bormans, L, Dormans, T, Dempsey, G, Mathew, S, Raj, A, Grecu, I, Cupitt, J, Lawton, T, Clark, R, Popescu, M, Spittle, N, Faulkner, M, Cowton, A, Elloway, E, Williams, P, Reay, M, Chukkambotla, S, Kumar, R, Al-Subaie, N, Kent, L, Tamm, T, Kajtor, I, Burns, K, Pugh, R, Ostermann, M, Kam, E, Bowyer, H, Smith, N, Templeton, M, Henning, J, Goffin, K, Kapoor, R, Laha, S, Chilton, P, Khaliq, W, Crayford, A, Coetzee, S, Tait, M, Stoker, W, Gimenez, M, Pope, A, Camsooksai, J, Pogson, D, Quigley, K, Ritzema, J, Hormis, A, Boulanger, C, Balasubramaniam, M, Vamplew, L, Burt, K, Martin, D, Craig, J, Prowle, J, Doyle, N, Shelton, J, Scott, C, Donnison, P, Shelton, S, Frey, C, Ryan, C, Spray, D, Barnes, V, Barnes, K, Ridgway, S, Saha, R, Clark, T, Wood, J, Bolger, C, Bassford, C, Lewandowski, J, Zhao, X, Humphreys, S, Dowling, S, Richardson, N, Burtenshaw, A, Stevenson, C, Wilcock, D, Nalapko, Y, de Lange D.W., Brinkman S., Flaatten H., Boumendil A., Morandi A., Andersen F.H., Artigas A., Bertolini G., Cecconi M., Christensen S., Faraldi L., Fjolner J., Jung C., Marsh B., Moreno R., Oeyen S., Ohman C.A., Bollen Pinto B., de Smet A.M.G.A., Soliman I.W., Szczeklik W., Valentin A., Watson X., Zafeiridis T., Guidet B., Schmutz R., Wimmer F., Eller P., Joannidis M., De Buysscher P., De Neve N., Swinnen W., Abraham P., Hergafi L., Schefold Joerg.C., Biskup E., Piza P., Taliadoros I., Dey N., Solling C., Rasmussen B.S., Forceville X., Besch G., Mentec H., Michel P., Mateu P., Vettoretti L., Bourenne J., Marin N., Guillot M., Aissaoui N., Goulenok C., Thieulot-Rolin N., Messika J., Lamhaut L., Charron C., Lauten A., Sacher A.L., Brenner T., Franz M., Bloos F., Ebelt H., Schaller S.J., Fuest Kristina., Rabe C., Dieck T., Steiner S., Graf T., Nia A.M., Janosi R.A., Meybohm P., Simon P., Utzolino S., Rahmel T., Barth E., Schuster M., Aidoni Z., Aloizos S., Tasioudis P., Lampiri K., Zisopoulou V., Ravani I., Pagaki E., Antoniou A., Katsoulas T.A., Kounougeri A., Marinakis G., Tsimpoukas F., Spyropoulou A., Zygoulis P., Kyparissi A., Gupta M., Gurjar M., Maji I.M., Hayes I., Kelly Y., Westbrook A., Fitzpatrick G., Maheshwari D., Motherway C., Negri G., Spadaro S., Nattino G., Pedeferri M., Boscolo A., Rossi S., Calicchio G., Cubattoli L., Di Lascio G., Barbagallo M., Berruto F., Codazzi D., Bottazzi A., Fumagalli P., Negro G., Lupi G., Savelli F., Vulcano Giuseppe.A., Fumagalli R., Marudi A., Lefons U., Lembo R., Babini M., Paggioro A., Parrini V., Zaccaria M., Clementi S., Gigliuto C., Facondini F., Pastorini S., Munaron S., Calamai I., Bocchi A., Adorni A., Bocci M.G., Cortegiani A., Casalicchio T., Mellea S., Graziani E., Barattini M., Brizio E., Rossi M., Hahn M., Kemmerer N., Strietzel H.F., Dybwik K., Legernaes T., Klepstad P., Olaussen E.B., Olsen K.I., Brresen O.M., Bjorsvik G., Maini S., Fehrle L., Czuczwar M., Krawczyk P., Zietkiewicz M., Nowak L.R., Kotfis K., Cwyl K., Gajdosz R., Biernawska J., Bohatyrewicz Romuald., Gawda R., Grudzien P., Nasilowski P., Popek N., Cyrankiewicz W., Wawrzyniak K., Wnuk M., Maciejewski D., Studzinska D., Zukowski M., Bernas S., Piechota M., Nowak I., Fronczek J., Serwa M., Machala W., Stefaniak J., Wujtewicz M., Maciejewski P., Szymkowiak M., Adamik B., Catorze N., Branco M.C., Barros I., Barros N., Krystopchuk A., Honrado T., Sousa C., Munoz F., Rebelo M., Gomes R., Nunes J., Dias Celeste., Fernandes A.M., Petrisor C., Constantin B., Belskiy V., Boskholov B., Rodriguez E., Rebollo S., Aguilar G., Masdeu G., Jaimes M.I., Mira A.P., Bodi Maria.A., Mendoza J.A.B., Cuenca S.L., Guzman M.H., Rico-Feijoo J., Ibarz M., Alvarez J.T., Kawati R., Sivik J., Nauska J., Smole D., Parenmark F., Lyren J., Rockstroh K., Ryden S., Strinnholm M., Walther S., De Geer L., Nordlund P., Palsson S., Zetterquist H., Nilsson A., Thiringer K., Jungner M., Bark B., Nordling B., Skold H., Brorsson C., Persson S., Bergstrom A., Berkius J., Holmstrom J., van Dijk I., van Lelyveld-Haas L.E.M., Ramnarain D., Jansen T., Nooteboom F., van der Voort P.H.J., Dieperink W., de Waard M.C., Bormans L., Dormans Tom., Dempsey G., Mathew S.J., Raj A.S., Grecu I., Cupitt J., Lawton T., Clark R., Popescu M., Spittle N., Faulkner M., Cowton A., Elloway E., Williams P., Reay M., Chukkambotla S., Kumar R., Al-Subaie N., Kent L., Tamm T., Kajtor I., Burns K., Pugh R., Ostermann M., Kam E., Bowyer H., Smith N., Templeton M., Henning J., Goffin K., Kapoor R., Laha S., Chilton P., Khaliq W., Crayford A., Coetzee S., Tait M., Stoker W., Gimenez M., Pope A., Camsooksai J., Pogson D., Quigley K., Ritzema J., Hormis A., Boulanger C., Balasubramaniam M., Vamplew L., Burt K., Martin D., Craig J., Prowle J., Doyle N., Shelton J., Scott Carmen., Donnison P., Shelton S., Frey C., Ryan C., Spray D., Barnes V., Barnes K., Ridgway S., Saha R., Clark T., Wood J., Bolger C., Bassford C., Lewandowski J., Zhao X., Humphreys S., Dowling S., Richardson N., Burtenshaw A., Stevenson C., Wilcock D., Nalapko Y., University Medical Center [Utrecht], University of Amsterdam [Amsterdam] (UvA), Public Health Service of Amsterdam, University of Bergen (UiB), Haukeland University Hospital, Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Universitat Autònoma de Barcelona (UAB), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Aarhus University Hospital, Centro Hospitalar de Lisboa Central E.P.E, Ghent University Hospital, Karolinska University Hospital [Stockholm], Geneva University Hospital (HUG), University Medical Center Groningen [Groningen] (UMCG), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), VIP1 Study Group (Beitragende*r), and Janosi, Rolf Alexander (Beitragende*r)
Subjects: Male, INTENSIVE-CARE-UNIT, Organ Dysfunction Scores, medicine.medical_treatment, Prognosis, Medizin, DECISION-MAKING, Logistic regression, law.invention, older adult, 0302 clinical medicine, PHYSICIANS, Interquartile range, law, 80 and over, Medicine and Health Sciences, 030212 general & internal medicine, Hospital Mortality, Prospective Studies, Prospective cohort study, older adults, Aged, 80 and over, predict, ddc:617, Respiration, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Brief Report, Intensive care unit, ADMISSION, 3. Good health, Europe, Hospitalization, Intensive Care Units, Brier score, Older adults, Artificial, Female, prognosi, medicine.medical_specialty, critical care, model, prognosis, Humans, Respiration, Artificial, 03 medical and health sciences, Intensive care, medicine, Journal Article, ILL ELDERLY-PATIENTS, Renal replacement therapy, Aged, Receiver operating characteristic, business.industry, 030208 emergency & critical care medicine, Emergency medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Brief Reports, Geriatrics and Gerontology, business
Abstract: OBJECTIVES To develop a scoring system model that predicts mortality within 30 days of admission of patients older than 80 years admitted to intensive care units (ICUs). DESIGN Prospective cohort study. SETTING A total of 306 ICUs from 24 European countries. PARTICIPANTS Older adults admitted to European ICUs (N = 3730; median age = 84 years [interquartile range = 81‐87 y]; 51.8% male). MEASUREMENTS Overall, 24 variables available during ICU admission were included as potential predictive variables. Multivariable logistic regression was used to identify independent predictors of 30‐day mortality. Model sensitivity, specificity, and accuracy were evaluated with receiver operating characteristic curves. RESULTS The 30‐day‐mortality was 1562 (41.9%). In multivariable analysis, these variables were selected as independent predictors of mortality: age, sex, ICU admission diagnosis, Clinical Frailty Scale, Sequential Organ Failure Score, invasive mechanical ventilation, and renal replacement therapy. The discrimination, accuracy, and calibration of the model were good: the area under the curve for a score of 10 or higher was .80, and the Brier score was .18. At a cut point of 10 or higher (75% of all patients), the model predicts 30‐day mortality in 91.1% of all patients who die. CONCLUSION A predictive model of cumulative events predicts 30‐day mortality in patients older than 80 years admitted to ICUs. Future studies should include other potential predictor variables including functional status, presence of advance care plans, and assessment of each patient's decision‐making capacity. © 2019 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals, Inc. on behalf of The American Geriatrics Society. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Published: 2019
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23. A protocol for developing a core outcome set for ectopic pregnancy

Author: Krystle Y Chong, Annika Strandell, Kurt T. Barnhart, Jian Zhang, Ben W.J. Mol, Janneke van 't Hooft, James Duffy, Andrew W Horne, Sarah Solangon, Madelon van Wely, George Condous, Munira Oza, Davor Jurkovic, Pamela Ines Causa Andrieu, Maria Memtsa, Perrine Capmas, Femke Mol, Carolina Beatriz Chacon, Lan N. Vuong, James M. Kemper, Liesl de Waard, Center for Reproductive Medicine, ARD - Amsterdam Reproduction and Development, APH - Methodology, and APH - Personalized Medicine
Subjects: Medicine (General), medicine.medical_specialty, Consensus, Delphi Technique, Ectopic pregnancy, Modified delphi, Medicine (miscellaneous), Randomised controlled trials, Outcome (game theory), Likert scale, Study Protocol, R5-920, Pregnancy, Modified Delphi method, Outcome Assessment, Health Care, Humans, Medicine, Pharmacology (medical), Set (psychology), Protocol (science), business.industry, Lived experience, Core outcome set, medicine.disease, Pregnancy, Ectopic, Core (game theory), Treatment Outcome, Consensus study, Research Design, Family medicine, Female, business
Abstract: Background Randomised controlled trials (RCTs) evaluating ectopic pregnancy have reported many different outcomes, which are themselves often defined and measured in distinct ways. This level of variation results in an inability to compare results of individual RCTs. The development of a core outcome set to ensure outcomes important to key stakeholders are collected consistently will guide future research in ectopic pregnancy. Study aim To develop and implement a core outcome set to guide future research in ectopic pregnancy. Methods and analysis We have established an international steering group of key stakeholders, including healthcare professionals, researchers, and individuals with lived experience of ectopic pregnancy. We will identify potential outcomes from ectopic pregnancy from a comprehensive literature review of published randomised controlled trials. We will then utilise a modified Delphi method to prioritise outcomes. Subsequently, key stakeholders will be invited to score potential core outcomes on a nine-point Likert scale, ranging from 1 (not important) to 9 (critical). Repeated reflection and rescoring should promote whole and individual stakeholder group convergence towards consensus ‘core’ outcomes. We will also establish standardised definitions and recommend high-quality measurements for individual core outcomes. Trial registration COMET 1492. Registered in November 2019.
Published: 2021
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24. Relationship of age, atherosclerosis and angiographic stenosis using artificial intelligence

Author: Hyuk Jae Chang, Todd C. Villines, Jung Hyun Choi, Gianluca Pontone, Michiel J. Bom, Hugo Marques, James J. Jang, Chris Rowan, Ryo Nakazato, Mouaz H. Al-Mallah, Bin Lu, Chang-Wook Nam, Muhammad Akram Khan, Ae-Young Her, Joon-Hyung Doh, Roel S. Driessen, Paul Knaapen, Sanghoon Shin, Robert S Jennings, Hyung-Bok Park, Guus A. de Waard, U. Joseph Schoepf, Randall C. Thompson, Tami R Crabtree, Yang Gao, Philippe Généreux, Alessia Gimelli, Andrew D. Choi, Faisal Nabi, Jason H. Cole, James K. Min, Erick Avelar, Michael Ridner, Bon Kwon Koo, James P. Earls, Daniele Andreini, Rebecca A Jonas, NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), Comprehensive Health Research Centre (CHRC) - pólo NMS, Cardiology, ACS - Atherosclerosis & ischemic syndromes, and ACS - Heart failure & arrhythmias
Subjects: Coronary angiography, Male, Myocardial ischemia, diagnostic imaging, Computed Tomography Angiography, Coronary Artery Disease, Coronary Angiography, Severity of Illness Index, Computed tomographic, Lesion, Artificial Intelligence, Predictive Value of Tests, medicine, Humans, Diseases of the circulatory (Cardiovascular) system, Prospective Studies, Computed tomography angiography, Aged, medicine.diagnostic_test, business.industry, Incidence, carotid artery diseases, Coronary Stenosis, Lesion types, Middle Aged, medicine.disease, Coronary Vessels, Plaque, Atherosclerotic, United States, Invasive coronary angiography, Stenosis, RC666-701, Female, Artificial intelligence, medicine.symptom, coronary angiography, atherosclerosis, business, Cardiology and Cardiovascular Medicine, computed tomography angiography, Follow-Up Studies
Abstract: ObjectiveThe study evaluates the relationship of coronary stenosis, atherosclerotic plaque characteristics (APCs) and age using artificial intelligence enabled quantitative coronary computed tomographic angiography (AI-QCT).MethodsThis is a post-hoc analysis of data from 303 subjects enrolled in the CREDENCE (Computed TomogRaphic Evaluation of Atherosclerotic Determinants of Myocardial IsChEmia) trial who were referred for invasive coronary angiography and subsequently underwent coronary computed tomographic angiography (CCTA). In this study, a blinded core laboratory analysing quantitative coronary angiography images classified lesions as obstructive (≥50%) or non-obstructive (ResultsThe cohort was 64.4±10.2 years and 29% women. Overall, patients >65 had more PV and CP than patients 65 had more CP than younger patients in both obstructive (29.2 mm3 vs 48.2 mm3; p3 vs 49.4 mm3; pConclusionAI-QCT identifies a unique APC signature that differs by age and degree of stenosis and provides a foundation for AI-guided age-based approaches to atherosclerosis identification, prevention and treatment.
Published: 2021
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25. Pneumococcal Carriage Among Indigenous Kichwa Children From the Ecuadorian Andes After the 10-Valent Pneumococcal Vaccine Introduction

Author: Daniela, Regalado L, Ismar A, Rivera-Olivero, Miguel Angel, Garcia-Bereguiain, Leandro, Tana, Isabel, Hernandez, Jeannete, Zurita, Jorge E, Vidal, Enrique, Terán, and Jacobus H, de Waard
Subjects: Adult, Male, Adolescent, Vaccination, Microbial Sensitivity Tests, Middle Aged, Serogroup, Pneumococcal Infections, Anti-Bacterial Agents, Pneumococcal Vaccines, Young Adult, Streptococcus pneumoniae, Caregivers, Child, Preschool, Drug Resistance, Multiple, Bacterial, Nasopharynx, Carrier State, Humans, Female, Ecuador, Child, Indigenous Peoples
Abstract: We assessed nasopharyngeal pneumococcal carriage in Andean Kichwa children, the largest Amerindian indigenous population in the Ecuadorian Andes. All children in our study had been vaccinated with the 10-valent pneumococcal vaccine (PCV10).Nasopharyngeal swabs from 63 families, 100 children10 years old including 38 children under 5 years and 63 adult caregivers, from 5 different communities, were cultivated for Streptococcus pneumoniae and isolates were serotyped and antibiotic susceptibility testing was performed.Respectively, 67% of the 38 children under 5 years old, 49% of the 62 children between 6 and 10 years old and 16% of the 100 adults were colonized with S. pneumoniae. Of these, 30.9% carried a vaccine serotype, 5.4% a serotype shared by the PCV10/13-valent pneumococcal vaccine (PCV13) vaccine and 25.5% a PCV13 serotype or PCV13 vaccine-related serotype, with 19A (10.9%) and 6C (10.9%) as the most prominent. Drug susceptibility testing revealed that 46% of the S. pneumoniae strains were susceptible to 6 tested antibiotics. However, 20.3% of the strains were multidrug-resistant or extensively drug-resistant strains, including 82% of the vaccine (-related) serotype 19A and 6C strains.Kichwa children, vaccinated with PCV10, were highly colonized with pneumococci and should be considered a high-risk group for pneumococcal disease. Twenty-five percent of the colonizing S. pneumoniae strains were PCV13-only vaccine-targeted serotypes, and in addition to that, most were multidrug-resistant or extensively drug-resistant strains. The vaccine benefits for this population possibly will significantly increase with the introduction of PCV13.
Published: 2021

26. Aortic distensibility in Marfan syndrome

Author: Aeilko H. Zwinderman, Arthur J.H.A. Scholte, Maarten P. van den Berg, Mitzi M van Andel, Janneke Timmermans, Vivian de Waard, M. Groenink, Barbara J. M. Mulder, Medical Biochemistry, ACS - Atherosclerosis & ischemic syndromes, Epidemiology and Data Science, APH - Methodology, Cardiology, ACS - Heart failure & arrhythmias, APH - Aging & Later Life, APH - Personalized Medicine, and Cardiovascular Centre (CVC)
Subjects: Adult, Male, Marfan syndrome, medicine.medical_specialty, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Magnetic Resonance Imaging, Cine, Aorta, Thoracic, Young Adult, All institutes and research themes of the Radboud University Medical Center, Vascular Stiffness, Aneurysm, Internal medicine, medicine.artery, MAGNETIC-RESONANCE, Diseases of the circulatory (Cardiovascular) system, Humans, Medicine, magnetic resonance imaging, Patient group, Retrospective Studies, Aorta, Aortic Aneurysm, Thoracic, medicine.diagnostic_test, Clinical events, business.industry, STIFFNESS, Magnetic resonance imaging, dissecting, Aortic and Vascular Disease, medicine.disease, RC666-701, Descending aorta, cardiovascular system, Cardiology, aneurysm, Female, Cardiology and Cardiovascular Medicine, business, Cardiac magnetic resonance, Follow-Up Studies
Abstract: ObjectivesPatients with Marfan syndrome (MFS) are prone to develop aortic aneurysms due to fragmentation of elastic fibres, resulting in reduced distensibility of the aorta. Reduced distensibility was previously shown to predict progressive descending aorta dilatation. Here, we investigated longitudinal changes in distensibility, as a potential predictor of aortic events.MethodsThis retrospective study included all patients with MFS with at least four cardiac magnetic resonance examinations performed between 1996 and 2012. Aortic distensibility was assessed, in the ascending (level 1), proximal descending (level 2) and distal descending (level 3) aorta. Changes in distensibility were studied using linear mixed-effects regression models.ResultsIn total, 35 patients with MFS (age at inclusion 28 (IQR 23–32) years, 54% men) were included. Mean aortic distensibility was already low (between 2.9×10–3/mm Hg/year and 6.4×10–3/mm Hg/year) at all levels at baseline, and significantly decreased over time at levels 2 and 3 (respectively, p=0.012 and p=0.002). The rate of distensibility loss per year (×10-3/mm Hg/year) was 0.01, 0.03 and 0.06×10–3/mm Hg at levels 1, 2 and 3, respectively. At inclusion, men exhibited very low distensibility, whereas women showed moderately reduced distensibility, gradually decreasing with age.Aortic dilatation rate at level 2 was associated with reduced aortic distensibility. However, we could not demonstrate a direct correlation between distensibility and clinical events during a follow-up of 22 years.ConclusionPatients with MFS display reduced aortic distensibility already at an early age, inversely relating to aortic dilatation rate. However, in this selected patient group, distensibility seems less suitable as an individual predictor of aortic events.
Published: 2021

27. Adverse Plaque Characteristics Relate More Strongly With Hyperemic Fractional Flow Reserve and Instantaneous Wave-Free Ratio Than With Resting Instantaneous Wave-Free Ratio

Author: James K. Min, Roel S. Driessen, Juhani Knuuti, Michiel J. Bom, Paul Knaapen, Wijnand J. Stuijfzand, Jonathon Leipsic, Niels van Royen, Justin E. Davies, Jagat Narula, Peter M. van de Ven, Amir Ahmadi, Pieter G. Raijmakers, Albert C. van Rossum, Ibrahim Danad, Guus A. de Waard, Cardiology, Radiology and nuclear medicine, Amsterdam Movement Sciences - Restoration and Development, ACS - Atherosclerosis & ischemic syndromes, Epidemiology and Data Science, ACS - Heart failure & arrhythmias, AMS - Tissue Function & Regeneration, and APH - Methodology
Subjects: Male, medicine.medical_specialty, Adenosine, Computed Tomography Angiography, Vasodilator Agents, Hemodynamics, Hyperemia, Perfusion scanning, Coronary Artery Disease, Fractional flow reserve, 030204 cardiovascular system & hematology, Coronary Angiography, medicine.disease_cause, Severity of Illness Index, 030218 nuclear medicine & medical imaging, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Internal medicine, Multidetector Computed Tomography, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Prospective Studies, Instantaneous wave-free ratio, Aged, business.industry, Coronary Stenosis, Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16], Middle Aged, medicine.disease, Vulnerable plaque, Plaque, Atherosclerotic, Fractional Flow Reserve, Myocardial, Coronary arteries, Stenosis, medicine.anatomical_structure, Cardiology, Female, Cardiology and Cardiovascular Medicine, business
Abstract: Contains fulltext : 229194.pdf (Publisher’s version ) (Closed access) OBJECTIVES: The current substudy of the PACIFIC (Prospective Comparison of Cardiac PET/CT, SPECT/CT Perfusion Imaging and CT Coronary Angiography With Invasive Coronary Angiography) trial explores the impact of computed tomography (CT)-derived unfavorable plaque features on both hyperemic and non-hyperemic flow indices. BACKGROUND: Next to lesion severity, plaque vulnerability as assessed using coronary CT angiography affects fractional flow reserve (FFR), which is associated with imminent acute coronary syndromes. Instantaneous wave-free ratio (iFR) has recently emerged as an alternative for FFR to interrogate coronary lesions for ischemia. It is, however, unknown whether vasodilator-free assessment with iFR is associated with plaque stability similarly as FFR. METHODS: Of 120 patients (62% men, age 58.3 +/- 8.6 years) with suspected coronary artery disease, 257 vessels were prospectively evaluated. Each patient underwent 256-slice coronary CT angiography to assess stenosis severity and plaque features (positive remodeling [PR], low attenuation plaque [LAP], spotty calcification [SC], and napkin ring sign [NRS]), as well as intracoronary pressure measurements (FFR, iFR, Pd/Pa, and pressure ratio during adenosine within the wave-free period [iFRa]). CT-derived plaque characteristics were related to these invasive pressure measurements. RESULTS: Atherosclerotic plaques were present in 170 (66%) coronary arteries. On a per-vessel basis, luminal stenosis severity was significantly associated with impaired FFR, iFR, Pd/Pa, and iFRa. Multivariable analysis revealed that FFR and iFR were independently related to >/=70% stenosis (-0.10, p < 0.001 and -0.09, p = 0.003, respectively) and plaque volume (-0.02, p = 0.020 and -0.02, p = 0.030, respectively). Additionally, PR and SC were also independent predictors of an impaired FFR (-0.10, p < 0.001 and -0.07, p = 0.021, respectively), but adverse plaque characteristics were not independently related to the vasodilator-free iFR. CONCLUSIONS: CT-derived vulnerable plaque characteristics are independently associated with hyperemic flow indices as assessed with FFR and iFRa, but not with non-hyperemic indices such as iFR and Pd/Pa. These findings suggest that the effects of hyperemia on pressure-derived indices might depend not only on hemodynamic stenosis severity but also on plaque characteristics.
Published: 2020
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28. A Clinical Validation Study of Anatomical Risk Scoring for Procedural Stroke in Patients Treated by Carotid Artery Stenting in the International Carotid Stenting Study

Author: Peter J. Koudstaal, Aad van der Lugt, Martin M. Brown, Paul J. Nederkoorn, Mechteld M. Arnold, Evelien E. de Vries, Leo H. Bonati, Djurre D. de Waard, Gert J. de Borst, A. Huibers, Lukas C. van Dijk, Neurology, ACS - Atherosclerosis & ischemic syndromes, Amsterdam Neuroscience - Neurovascular Disorders, and Radiology & Nuclear Medicine
Subjects: Male, Aortic arch, medicine.medical_specialty, Computed Tomography Angiography, medicine.medical_treatment, Operative Time, Aorta, Thoracic, Context (language use), 030204 cardiovascular system & hematology, 030230 surgery, Risk Assessment, Blood Vessel Prosthesis Implantation, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, medicine.artery, Internal medicine, Preoperative Care, Post-hoc analysis, medicine, Humans, Carotid Stenosis, Intraoperative Complications, Stroke, Aged, Endarterectomy, Carotid, Framingham Risk Score, medicine.diagnostic_test, business.industry, Prognosis, medicine.disease, Atheroma, Angiography, Cardiology, Female, Stents, Surgery, Carotid stenting, Cardiology and Cardiovascular Medicine, business
Abstract: Objectives: Vascular anatomy of the aortic arch and supra-aortic arteries has been suggested as influencing the risk of carotid artery stenting (CAS). The expert opinion based Delphi anatomical risk (DAR) score was developed to predict difficulty of CAS in relation to procedural stroke risk, and thereby aid patient selection. The aim was to validate the DAR score in the context of a randomised clinical trial. Methods: In this post hoc analysis of the International Carotid Stenting Study (ICSS), only patients treated by CAS with available pre-procedural CT angiography (CTA) were included. Patients with tortuous anatomy unsuitable for stenting were excluded from ICSS. CTA based vascular anatomy was rated by two independent observers. Every possible combination of anatomy resulted in a risk score, divided in four categories of expected risk (low, < 5.0; low–intermediate, 5.0–5.9; high–intermediate, 6.0–6.9; high, ≥ 7.0). Binomial logistic regression was used to assess the relationship between anatomical risk score and procedural risk of any stroke. Differences between predefined age groups were also assessed. Results: A total of 275 patients were included. Interobserver reliability for all anatomical risk factors was high (κ = 0.76–0.84). In total, 16 strokes (6%) occurred in the procedural period. No significant relationship was observed between the DAR score and risk of procedural stroke, with the risk of stroke being 9% in the high risk vs. 4% in the low risk categories (p = .49). A higher mean DAR score was observed in patients ≥70 years compared with younger patients (4.6 ± 1.5 vs. 3.9 ± 1.4, p < .001), which was mainly explained by higher rates of arch atheroma (44% vs. 20%, p < .001). Prolonged intervention duration was significantly associated with increased stroke risk (11% vs. 4%, p < .04), but not with the DAR score. Conclusions: No statistically significant association was found between anatomical difficulty, as defined in the DAR score, and procedural stroke risk. However, the small sample size potentially rendered the study underpowered to detect group differences, and confirmation with a larger sample is essential.
Published: 2019
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29. Exercise responses in children and adults with a Fontan circulation at simulated altitude

Author: Christian Schroer, Erik H. J. Hulzebos, Alyanne Evertse, Mandy Spoorenburg, Martijn Kuijpers, Fleur de Waard, and Tim Takken
Subjects: Male, Cardiac output, Time Factors, Hemodynamics, 030204 cardiovascular system & hematology, Fontan Procedure, Pediatrics, 0302 clinical medicine, Heart Rate, Fontan circulation, Respiratory system, acute high altitude, Cardiac Output, Child, Hypoxia, Exercise Tolerance, exercise, Altitude, Respiration, Age Factors, General Medicine, Effects of high altitude on humans, Perinatology, and Child Health, Treatment Outcome, Cardiorespiratory Fitness, Radiology Nuclear Medicine and imaging, Cardiology, Original Article, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, Adult, Heart Defects, Congenital, medicine.medical_specialty, Adolescent, 03 medical and health sciences, Heart disorder, Young Adult, Simulated altitude, Oxygen Consumption, CPET, 030225 pediatrics, Internal medicine, medicine, Journal Article, Humans, Radiology, Nuclear Medicine and imaging, Pediatrics, Perinatology, and Child Health, business.industry, hypoxia, Original Articles, Hypoxia (medical), Case-Control Studies, Pediatrics, Perinatology and Child Health, Surgery, business
Abstract: Background Traveling to high altitude has become more popular. High‐altitude exposure causes hypobaric hypoxia. Exposure to acute high altitude, during air travel or mountain stays, seems to be safe for most patients with congenital heart disorders (CHD). Still, current guidelines for CHD patients express concerns regarding safety of altitude exposure for patients with a Fontan circulation. Therefore, investigating hemodynamic and pulmonary responses of acute high‐altitude exposure (±2500 m) at rest and during maximal exercise in patients with Fontan circulation can provide clarity in this dispute and may contribute to improvement of clinical counseling. Methods Twenty‐one Fontan patients with 21 age‐matched healthy controls, aged 8‐40 years, were enrolled in an observational study. Participants performed two cardiopulmonary exercise tests on a cycle ergometer with breath‐by‐breath respiratory gas analyses combined with noninvasive impedance cardiac output measurements: one at sea level (±6 m) and one at simulated high altitude (±2500 m), respectively. Results The effect of altitude exposure was different in rest for saturation (−2.3% vs −4.1%) between Fontan patients and healthy controls (P
Published: 2019

30. Screening for distant metastases in patients with ipsilateral breast tumor recurrence

Author: Poodt, Ingrid G. M., Schipper, Robert-Jan, de Greef, Bianca T. A., Vugts, Guusje, Maaskant-Braat, Adriana J. G., Jansen, Frits H., Wyndaele, Dirk N. J., Voogd, Adri C., Nieuwenhuijzen, Grard A. P., Roumen, R. M. H., Luiten, E. J. T., Rutgers, E. J. T., Vrancken-Peeters, M. T. F. D., Bessems, M., Klaase, J. M., Muller, S., Francken, A. B., Van Dalen, T., Koopal, S. A., Vissers, Y. L. J., Smidt, M. L., Merkus, J. W. S., Contant, C. M. E., Veldman, P. H., Linthorst-Niers, E. M. H., van der Sijp, J. R., Guicherit, O. R., Koppert, L. B., Bosch, A. M., Strobbe, L. J. A., Schlooz-Vries, M. S., Arntz, I. E., van Essen, J. A., de Waard, J. W. D., Vrouenraets, B. C., van Ooijen, B., Smidt, Marjolein, Groningen Institute for Organ Transplantation (GIOT), Value, Affordability and Sustainability (VALUE), Klinische Neurowetenschappen, MUMC+: KIO Kemta (9), RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, RS: MHeNs - R3 - Neuroscience, Epidemiologie, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Surgery, and MUMC+: MA Heelkunde (9)
Subjects: 0301 basic medicine, Cancer Research, Palliative care, PROGNOSIS, medicine.medical_treatment, ACCURACY, Scintigraphy, Multimodal Imaging, 0302 clinical medicine, Breast cancer, Positron Emission Tomography Computed Tomography, Breast, FDG-PET, Early Detection of Cancer, Mastectomy, Netherlands, Aged, 80 and over, medicine.diagnostic_test, 18F-FDG PET-CT, Liver Neoplasms, Palliative Care, Middle Aged, Sentinel node, Propensity score weight, Clinical Trial, Combined Modality Therapy, F-18-FDG PET-CT, PROPENSITY SCORE, Oncology, Positron emission tomography, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Distant metastasis, Female, Radiology, Adult, Conventional imaging, medicine.medical_specialty, Breast Neoplasms, Preoperative screening, 03 medical and health sciences, POSITRON-EMISSION-TOMOGRAPHY, Fluorodeoxyglucose F18, medicine, Humans, COMPUTED-TOMOGRAPHY, CANCER PATIENTS, Radionuclide Imaging, SURGICAL ADJUVANT BREAST, Aged, Neoplasm Staging, LOCOREGIONAL RECURRENCES, Proportional hazards model, business.industry, medicine.disease, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], 030104 developmental biology, Ipsilateral breast tumor recurrence, SENTINEL NODE, Neoplasm Recurrence, Local, business
Abstract: Purpose In patients with ipsilateral breast tumor recurrence (IBTR), the detection of distant disease determines whether the intention of the treatment is curative or palliative. Therefore, adequate preoperative staging is imperative for optimal treatment planning. The aim of this study is to evaluate the impact of conventional imaging techniques, including chest X-ray and/or CT thorax-(abdomen), liver ultrasonography(US), and skeletal scintigraphy, on the distant recurrence-free interval (DRFI) in patients with IBTR, and to compare conventional imaging with 18F-FDG PET-CT or no imaging at all. Methods This study was exclusively based on the information available at time of diagnoses of IBTR. To adjust for differences in baseline characteristics between the three imaging groups, a propensity score (PS) weighted method was used. Results Of the 495 patients included in the study, 229 (46.3%) were staged with conventional imaging, 89 patients (19.8%) were staged with 18F-FDG PET-CT, and in 168 of the patients (33.9%) no imaging was used (N = 168). After a follow-up of approximately 5 years, 14.5% of all patients developed a distant recurrence as first event after IBTR. After adjusting for the PS weights, the Cox regression analyses showed that the different staging methods had no significant impact on the DRFI. Conclusions This study showed a wide variation in the use of imaging modalities for staging IBTR patients in the Netherlands. After using PS weighting, no statistically significant impact of the different imaging modalities on DRFI was shown. Based on these results, it is not possible to recommend staging for distant metastases using 18F-FDG PET-CT over conventional imaging techniques. Electronic supplementary material The online version of this article (10.1007/s10549-019-05205-z) contains supplementary material, which is available to authorized users.
Published: 2019

31. Renal Resistive Index: Response to Shock and its Determinants in Critically Ill Patients

Author: Jelle L G Haitsma Mulier, Sander Rozemeijer, Heleen M. Oudemans-van Straaten, Pieter R. Tuinman, Angelique M. E. Spoelstra-de Man, Paul W. G. Elbers, Monique C. de Waard, Jantine G Röttgering, Intensive care medicine, ACS - Diabetes & metabolism, AII - Inflammatory diseases, ACS - Atherosclerosis & ischemic syndromes, and ACS - Pulmonary hypertension & thrombosis
Subjects: cardiac index, Male, estimated glomerular filtration rate, RRI, SDF, shock, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Clinical Science Aspects, Doppler ultrasound, intensive care unit, sidestream dark field, HI, Cohort Studies, Xc, 0302 clinical medicine, HR, eGFR, heart rate, SIRS, Prospective Studies, Prospective cohort study, interclass correlation coefficient, APACHE, intensive care, pulse pressure index, venous oxygen saturation, central venous pressure, Central venous pressure, Acute kidney injury, FENa, CI, Acute Kidney Injury, Middle Aged, Pulse pressure, CVP, systemic inflammatory response syndrome, predictive mean matching, standard error, Shock (circulatory), Emergency Medicine, Cardiology, MAP, mean arterial pressure, Female, medicine.symptom, standard deviation, Cohort study, microvascular flow index, medicine.medical_specialty, Mean arterial pressure, MFI, PPI, Critical Illness, VP, perfused vessel density, Renal function, microcirculation, PPV, vasopressor, fractional excretion of sodium, resistance, 03 medical and health sciences, AKI, Internal medicine, BIA, vessel density, bioimpedance, medicine, Humans, proportion of perfused vessels, FEUrea, SE, SD, Aged, bioelectral impedance analysis, PMM, business.industry, ICC, fractional excretion of urea, renal resistive index, IC, 030208 emergency & critical care medicine, medicine.disease, heterogeneity index, PVD, VD, acute physiology and chronic health evaluation, ICU, SvO2, bioelectral impedance-derived reactance (membrane capacitance), business, human activities
Abstract: INTRODUCTION: Shock is characterised by micro- and macrovascular flow impairment contributing to acute kidney injury (AKI). Routine monitoring of the circulation regards the macrocirculation but not the renal circulation which can be assessed with Doppler ultrasound as renal resistive index (RRI). RRI reflects resistance to flow. High RRI predicts persistent AKI. Study aims were to determine whether RRI is elevated in shock and to identify determinants of RRI.MATERIALS AND METHODS: This prospective observational cohort study included two cohorts of patients, with and without shock RESULTS: 92 patients were included (40 shock, 52 non-shock), median age was 69 [60-76] vs. 67 [59-76], p = 0.541; APACHE III was 87 [65-119] vs. 57 [45-69], p CONCLUSIONS: Patients with shock have a higher RRI than patients without. Independent determinants of high RRI were pressure indices of the systemic circulation, low membrane capacitance and pre-admission renal dysfunction. Markers of the sublingual microcirculation were not. TRIAL REGISTRATION CLINICALTRIALS.GOV:: NCT02558166.DATE OF REGISTRATION: 22-09-2015, retrospectively registeredThis is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.
Published: 2019
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32. Clinical auditing as an instrument to improve care for patients with ovarian cancer

Author: N. Leffers, H.T.C. Nagel, Roy F.P.M. Kruitwagen, R.A. Smit, F.A. Ten Cate, A.D. Ten Cate, S.F.P.J. Coppus, A.M.L.D. Van Haaften-de Jong, J.H.A. Vollebergh, M.J.A. Engelen, Eva Maria Roes, L.C. De Vries, P.J. Timmers, E.A. Ooms, J. Diepstraten, G.H. Jansen, W. Minderhoud-Bassie, N.M.S. Baldewpersad Tewarie, M.I. Baas, M.A. van der Aa, M. van Ham, A.J. Kruse, T.K. Schikken, T.C. Stam, I.M.W. Ebisch, J.A. Louwers, J.W. Mens, A.M.G. van de Swaluw, E. Davelaar, C.G. Gerestein, M.W. Glas, R. van de Laar, B.A.J.T. Visschers, H.P.M. Smedts, W.J. van Driel, E.B.L. van Dorst, R. Yigit, M.W.G. Moonen Delarue, W.M. van Baal, Y.W.C.M. Van der Plas – Koning, M.Y. Tjiong, L.R. Bartelink, F.M.F. Rosier-van Dunné, M.B. Verbruggen, J.G. Lange, Michel W.J.M. Wouters, C.M.W.H. Smeets, G. Fons, F.E.M. Rijcken, H.R. Verhoeve, J.W.D. de Waard, E.J.M. Van Es, J.E.W. Van Dijk, J. Briet, C.C.M. Buis, K. Overmars, A. van der Kolk, M. Kleppe, M.A. Huisman, P. Kolk, E.J.M. Robbe, M. van den Hende, M. Huisman, Brigitte F. M. Slangen, A.L. Aalders, S.M. Westenberg, H.H. Keizer, M.C. Vos, A. Baalbergen, L.N. Hofman, J. Kaijser, D. Boll, N. Reesink, D. Boskamp, P.M.L.H. Vencken, K.N. Gaarenstroom, D.H. Ngo, M.D. Wust, Gynecological Oncology, Radiotherapy, Obstetrie & Gynaecologie, MUMC+: MA Obstetrie Gynaecologie (3), MUMC+: Vrouw Moeder en Kind Centrum (3), MUMC+: MA Arts Assistenten Obstetrie Gynaecologie (9), MUMC+: MA Toegelatenen Obstetrie Gynaecologie (9), RS: GROW - R2 - Basic and Translational Cancer Biology, MUMC+: MA Medische Staf Obstetrie Gynaecologie (9), Epidemiology and Data Science, APH - Aging & Later Life, APH - Societal Participation & Health, Obstetrics and gynaecology, Amsterdam Reproduction & Development (AR&D), Targeted Gynaecologic Oncology (TARGON), Obstetrics and Gynaecology, and CCA - Cancer Treatment and Quality of Life
Subjects: Clinical audit, Adult, medicine.medical_specialty, Commission on professional and hospital activities, Adolescent, SURGERY, Best practice, SOCIETY, Quality indicators, Audit, 030230 surgery, 03 medical and health sciences, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, Health care, Commission on professional and hospital, CENTRALIZATION, Medicine, Humans, Registries, Quality of care, Aged, Netherlands, Aged, 80 and over, Ovarian Neoplasms, activities, Gynecological oncology, OUTCOMES, Medical Audit, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], business.industry, Gynecologic neoplasms, General Medicine, Cytoreduction Surgical Procedures, Middle Aged, medicine.disease, Quality Improvement, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], Case ascertainment, Oncology, 030220 oncology & carcinogenesis, Family medicine, INSTITUTE, Female, business, Ovarian cancer
Abstract: Introduction: The Dutch Gynecological Oncology Audit (DGOA) was initiated in 2014 to serve as a nationwide audit, which registers the four most prevalent gynecological malignancies. This study presents the first results of clinical auditing for ovarian cancer in the Netherlands.Methods: The Dutch Gynecological Oncology Audit is facilitated by the Dutch Institute of Clinical Auditing (DICA) and run by a scientific committee. Items are collected through a web-based registration based on a set of predefined quality indicators. Results of quality indicators are shown, and benchmarked information is given back to the user. Data verification was done in 2016. Results: Between January 01, 2014 and December 31, 2018, 6535 patients with ovarian cancer were registered. The case ascertainment was 98.3% in 2016. The number of patients with ovarian cancer who start therapy within 28 days decreased over time from 68.7% in 2014 to 62.7% in 2018 (p < 0.001). The percentage of patients with primary cytoreductive surgery decreased over time (57.8%-39.7%, P < 0.001). However, patients with complete primary cytoreductive surgery improved over time (53.5%-69.1%, P < 0.001). Other quality indicators did not significantly change over time.Conclusion: The Dutch Gynecological Oncology Audit provides valuable data on the quality of care on patients with ovarian cancer in the Netherlands. Data show variation between hospitals with regard to pre-determined quality indicators. Results of 'best practices' will be shared with all participants of the clinical audit with the aim of improving quality of care nationwide.(c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license(http://creativecommons.org/licenses/by/4.0/).
Published: 2021
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33. A Novel Hypothesis: A Role for Follicle Stimulating Hormone in Abdominal Aortic Aneurysm Development in Postmenopausal Women

Author: Victoria N. Tedjawirja, Kak K. Yeung, Vivian de Waard, Max Nieuwdorp, Ron Balm, Surgery, Internal medicine, ACS - Diabetes & metabolism, AGEM - Endocrinology, metabolism and nutrition, ACS - Atherosclerosis & ischemic syndromes, ACS - Microcirculation, Graduate School, Experimental Vascular Medicine, Vascular Medicine, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Medical Biochemistry, and ACS - Heart failure & arrhythmias
Subjects: medicine.medical_specialty, endocrine system, Endocrinology, Diabetes and Metabolism, Adipose tissue, menopause, macromolecular substances, Diseases of the endocrine glands. Clinical endocrinology, Follicle-stimulating hormone, Aneurysm, Endocrinology, abdominal aortic aneurysm, medicine.artery, Internal medicine, Hypothesis and Theory, medicine, Humans, cardiovascular diseases, Aortic atherosclerosis, follicle stimulating hormone, Aorta, adiposity, business.industry, Abdominal aorta, RC648-665, medicine.disease, Prognosis, osteoporosis, Abdominal aortic aneurysm, macrophages, Menopause, Postmenopause, cardiovascular system, Female, women, atherosclerosis, business, Aortic Aneurysm, Abdominal
Abstract: An abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta, which can potentially be fatal due to exsanguination following rupture. Although AAA is less prevalent in women, women with AAA have a more severe AAA progression compared to men as reflected by enhanced aneurysm growth rates and a higher rupture risk. Women are diagnosed with AAA at an older age than men, and in line with increased osteoporosis and cardiovascular events, the delayed AAA onset has been attributed to the reduction of the protective effect of oestrogens during the menopausal transition. However, new insights have shown that a high follicle stimulating hormone (FSH) level during menopause may also play a key role in those diseases. In this report we hypothesize that FSH may aggravate AAA development and progression in postmenopausal women via a direct and/or indirect role, promoting aorta pathology. Since FSH receptors (FSHR) are reported on many other cell types than granulosa cells in the ovaries, it is feasible that FSH stimulation of FSHR-bearing cells such as aortic endothelial cells or inflammatory cells, could promote AAA formation directly. Indirectly, AAA progression may be influenced by an FSH-mediated increase in osteoporosis, which is associated with aortic calcification. Also, an FSH-mediated decrease in cholesterol uptake by the liver and an increase in cholesterol biosynthesis will increase the cholesterol level in the circulation, and subsequently promote aortic atherosclerosis and inflammation. Lastly, FSH-induced adipogenesis may lead to obesity-mediated dysfunction of the microvasculature of the aorta and/or modulation of the periaortic adipose tissue. Thus the long term increased plasma FSH levels during the menopausal transition may contribute to enhanced AAA disease in menopausal women and could be a potential novel target for treatment to lower AAA-related events in women.
Published: 2021
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34. Chemical Synthesis, Proper Folding, Na

Author: Sébastien, Nicolas, Claude, Zoukimian, Frank, Bosmans, Jérôme, Montnach, Sylvie, Diochot, Eva, Cuypers, Stephan, De Waard, Rémy, Béroud, Dietrich, Mebs, David, Craik, Didier, Boturyn, Michel, Lazdunski, Jan, Tytgat, and Michel, De Waard
Subjects: Voltage-Gated Sodium Channel Blockers, Analgesics, Protein Folding, pain target, NAV1.7 Voltage-Gated Sodium Channel, spider toxin, Pain, Spider Venoms, Spiders, Nav channel activity, CHO Cells, directed disulfide bond formation, Article, Mice, Inbred C57BL, Xenopus laevis, Cricetulus, Formaldehyde, Oocytes, Animals, Female, Amino Acid Sequence, Peptides, automated patch-clamp, Nav1.7
Abstract: Phlotoxin-1 (PhlTx1) is a peptide previously identified in tarantula venom (Phlogius species) that belongs to the inhibitory cysteine-knot (ICK) toxin family. Like many ICK-based spider toxins, the synthesis of PhlTx1 appears particularly challenging, mostly for obtaining appropriate folding and concomitant suitable disulfide bridge formation. Herein, we describe a procedure for the chemical synthesis and the directed sequential disulfide bridge formation of PhlTx1 that allows for a straightforward production of this challenging peptide. We also performed extensive functional testing of PhlTx1 on 31 ion channel types and identified the voltage-gated sodium (Nav) channel Nav1.7 as the main target of this toxin. Moreover, we compared PhlTx1 activity to 10 other spider toxin activities on an automated patch-clamp system with Chinese Hamster Ovary (CHO) cells expressing human Nav1.7. Performing these analyses in reproducible conditions allowed for classification according to the potency of the best natural Nav1.7 peptide blockers. Finally, subsequent in vivo testing revealed that intrathecal injection of PhlTx1 reduces the response of mice to formalin in both the acute pain and inflammation phase without signs of neurotoxicity. PhlTx1 is thus an interesting toxin to investigate Nav1.7 involvement in cellular excitability and pain.
Published: 2019

35. Ocular motility changes and diplopia in sutured versus unsutured implantation of the Baerveldt glaucoma device

Author: Caroline P. Jordaan-Kuip, Peter W.T. de Waard, Hans G Lemij, Koen A. Vermeer, and Esma Islamaj
Subjects: Male, medicine.medical_specialty, Eye Movements, genetic structures, medicine.medical_treatment, Visual Acuity, Glaucoma, surgical technique, Postoperative Complications, Ophthalmology, Diplopia, medicine, Glaucoma surgery, Humans, Prospective Studies, baerveldt, Glaucoma Drainage Implants, Prospective cohort study, Aged, Netherlands, business.industry, Incidence, Ocular motility, Suture Techniques, Significant difference, Original Articles, General Medicine, medicine.disease, eye diseases, Strabismus, glaucoma surgery, Hyperdeviation, Filtering Surgery, Original Article, Female, sense organs, Implant, medicine.symptom, business
Abstract: Purpose To investigate the effect of two surgical techniques in primary Baerveldt glaucoma implant (BGI) surgery, that is the sutured technique and the unsutured (free) plate technique, on the ocular motility and prevalence of diplopia. We hypothesize that the free plate technique results in a lower diplopia prevalence. Methods We performed a prospective study of patients who underwent BGI surgery with the free plate technique and compared them with patients from a previous study who had undergone BGI surgery with the sutured technique. Their ductions, ocular alignment and fusion range and the prevalence of diplopia were measured before surgery and at 3 months, 6 months and 1 year postoperatively. Results We analysed 57 free plate and 51 sutured plate patients. One year postoperatively, we found no statistically significant difference in the prevalence of diplopia between the two techniques. All duction changes between baseline and 1‐year follow‐up were restrictions and occurred statistically significantly more frequently in the free plate than in the sutured plate group (p = 0.03; 60% versus 34%). About the ocular alignment, in the horizontal direction, a change in exodirection was more common in both groups, while in the vertical direction, a hyperdeviation of the operated eye was more common. The vertical ocular alignment change was smaller in the free plate group than in the sutured plate group (p = 0.04 at near and p = 0.02 at distance). Conclusions One year postoperatively, the prevalence of diplopia was not significantly different between patients with the sutured plate and patients with the free plate technique. Both surgical techniques induce diplopia and changes in ocular motility and/or in ocular alignment.
Published: 2021
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36. Driving performance and neurocognitive skills of long‐term users of sedating antidepressants

Author: van der Sluiszen, Nick N J J M, Vermeeren, Annemiek, van Dijken, Joke H, J A E van de Loo, Aurora, Veldstra, Janet L, de Waard, Dick, C Verster, Joris, A Brookhuis, Karel, Ramaekers, Johannes G, Afd Pharmacology, dIRAS RA-1, Pharmacology, RS: FPN NPPP II, Section Psychopharmacology, Clinical Neuropsychology, Afd Pharmacology, dIRAS RA-1, and Pharmacology
Subjects: Male, long‐term use, neurocognition, Audiology, ACCIDENTS, ROAD, 0302 clinical medicine, on‐the‐road driving, Hypnotics and Sedatives, Amitriptyline, Pharmacology (medical), RISK, PLACEBO, PAIN, driving performance, Antidepressants, Middle Aged, Antidepressive Agents, Psychiatry and Mental health, Neurology, antidepressants, Antidepressant, Blood Alcohol Content, Female, DEPRESSED-PATIENTS, medicine.drug, Research Article, long-term use, medicine.medical_specialty, Automobile Driving, Driving test, Mirtazapine, Clinical Neurology, Placebo, 03 medical and health sciences, HYPNOTICS, medicine, Humans, DRUGS, Clinical significance, METAANALYSIS, business.industry, on-the-road driving, 030227 psychiatry, STANDARD-DEVIATION, Neurocognitive Tests, Neurology (clinical), business, Neurocognitive, 030217 neurology & neurosurgery, Psychomotor Performance
Abstract: Objective To assess driving performance and neurocognitive skills of long‐term users of sedating antidepressants, in comparison to healthy controls. Methods Thirty‐eight long‐term (>6 months) users of amitriptyline (n = 13) and mirtazapine (n = 25) were compared to 65 healthy controls. Driving performance was assessed using a 1‐h standardised highway driving test in actual traffic, with road‐tracking error (standard deviation of lateral position [SDLP]) being the primary measure. Secondary measures included neurocognitive tasks related to driving. Performance differences between groups were compared to those of blood alcohol concentrations of 0.5 mg/ml to determine clinical relevance. Results Compared to controls, mean increase in SDLP of all antidepressant users was not significant, nor clinically relevant (+0.75 cm, 95% CI: −0.83 cm; +2.33 cm). However, users treated less than 3 years (n = 20) did show a significant and clinically relevant increase in SDLP (+2.05 cm). No significant effects were observed on neurocognitive tasks for any user group, although large individual differences were present. Most results from neurocognitive tests were inconclusive, while a few parameters confirmed non‐inferiority for users treated longer than 3 years. Conclusion The impairing effects of antidepressant treatment on driving performance and neurocognition mitigate over time following long‐term use of 3 years.
Published: 2021

37. Implications of a Soy-Based Diet for Animal Models

Author: J. Dhot, Michel De Waard, Benjamin Lauzier, Virginie Aillerie, Valentine Prat, Bertrand Rozec, Angélique Erraud, Marine Ferron, and C. Gauthier
Subjects: Male, 0301 basic medicine, endothelium, Heart Ventricles, Rat model, Physiology, Phytoestrogens, 030204 cardiovascular system & hematology, Catalysis, Inorganic Chemistry, lcsh:Chemistry, 03 medical and health sciences, 0302 clinical medicine, Diastole, Male rats, Animals, Humans, Medicine, sex, Diastolic function, Physical and Theoretical Chemistry, Molecular Biology, lcsh:QH301-705.5, Spectroscopy, business.industry, Communication, Organic Chemistry, diastolic function, General Medicine, Animal Feed, Diet, Rats, Computer Science Applications, Clinical Practice, Disease Models, Animal, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, Receptors, Adrenergic, beta-3, soy-based diet, phytoestrogen, Female, Soybeans, Rats, Transgenic, business
Abstract: The use of animal models in fundamental or pre-clinical research remains an absolute requirement for understanding human pathologies and developing new drugs. In order to transpose these results into clinical practice, many parameters must be taken into account to limit bias. Attention has recently been focused on the sex, age or even strain of each animal, but the impact of diet has been largely neglected. Soy, which is commonly used in the diet in varying quantities can affect their physiology. In order to assess whether the presence of soy can impact the obtained results, we studied the impact of a soy-based diet versus a soy-free diet, on diastolic function in a rat model based on transgenic overexpression of the β3-adrenergic receptors in the endothelium and characterized by the appearance of diastolic dysfunction with age. Our results show that the onset of diastolic dysfunction is only observed in transgenic male rats fed with a soy-free diet in the long term. Our study highlights the importance of the diet’s choice in the study design process, especially regarding the proportion of soy, to correctly interpret the outcome as low-cost diets are more likely to be highly concentrated in soy.
Published: 2021

38. Postoperative outcomes of primary and interval cytoreductive surgery for advanced ovarian cancer registered in the Dutch Gynecological Oncology Audit (DGOA)

Author: MC Vos, H.T.C. Nagel, R.A. Smit, N. Reesink, A. Baalbergen, Eva Maria Roes, P.J. Timmers, Arnold-Jan Kruse, Jan Willem M. Mens, Mirjam J. A. Engelen, B.A.J.T. Visschers, T.C. Stam, H.P.M. Smedts, N.M.S. Baldewpersad Tewarie, A. van der Kolk, J. Lange, H. Verhoeve, Katja N. Gaarenstroom, Michel W.J.M. Wouters, Brigitte F. M. Slangen, I. Ebisch, Sjors F.P.J. Coppus, D. Boll, L. Hofman, C. G. Gerestein, Y.W.C.M. van der Plas-Koning, J. de Waard, A.M.L.D. van Haaften-de Jong, E.B.L. van Dorst, J. Diepstraten, A.D. Ten Cate, M.Y. Tjiong, M.A. van der Aa, R. Yigit, A.L. Aalders, R Kruitwagen, J. Briet, W.J. van Driel, M. van Ham, P.M.L.H. Vencken, M.B. Verbruggen, M. Huisman, Guus Fons, RS: GROW - R2 - Basic and Translational Cancer Biology, Obstetrie & Gynaecologie, MUMC+: MA Obstetrie Gynaecologie (3), MUMC+: MA Arts Assistenten Obstetrie Gynaecologie (9), MUMC+: Vrouw Moeder en Kind Centrum (3), Obstetrics and Gynaecology, CCA - Cancer Treatment and Quality of Life, Obstetrics and gynaecology, Amsterdam Reproduction & Development (AR&D), Epidemiology and Data Science, APH - Aging & Later Life, APH - Societal Participation & Health, Radiotherapy, and Gynecological Oncology
Subjects: 0301 basic medicine, Complications, DEBULKING SURGERY, Severity of Illness Index, DISEASE, NEOADJUVANT CHEMOTHERAPY, Postoperative Complications, 0302 clinical medicine, Netherlands, Aged, 80 and over, Ovarian Neoplasms, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], Geography, Obstetrics and Gynecology, Postoperative outcomes, Cytoreduction Surgical Procedures, Middle Aged, Debulking, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], Oncology, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, SURVIVAL, Female, Cytoreductive surgery, Adult, medicine.medical_specialty, Adolescent, Audit, Time-to-Treatment, Young Adult, 03 medical and health sciences, Case mix index, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, Time to adjuvant chemotherapy, medicine, Humans, Aged, Neoplasm Staging, Retrospective Studies, Advanced ovarian cancer, Gynecological oncology, business.industry, Confidence interval, Surgery, 030104 developmental biology, Cytroreductive surgery, Complication, business
Abstract: Objectives. The challenge when performing cytoreductive surgery (CRS) is to balance the benefits and risks. The aim of this study was to report short term postoperative morbidity and mortality in relation to surgical outcome in patients undergoing primary debulking surgery (PDS) or interval debulking (IDS) surgery in the Netherlands. Methods. The Dutch Gynecological Oncology Audit (DGOA) was used for retrospective analysis. Patients undergoing PDS or IDS between January 1st, 2015 -December 31st, 2018 were included. Outcome was frequency of postoperative complications. Median time to adjuvant chemotherapy and severity of complications were related to outcome of CRS. Complications with Clavien-Dindo >= 3 were analyzed per region and case mix corrected. Statistical analysis was performed with R.Studio. Results. 1027 patients with PDS and 1355 patients with IDS were included. Complications with re-invention were significantly higher in PDS compared to IDS (5.7% vs. 3.6%, p = 0.048). Complete cytoreduction was 69.7% in PDS and 62.1% IDS, p < 0.001. Time to adjuvant chemotherapy was 49 days in patients with complete CRS and a complication with re-intervention. Regional variation for severe complications showed one region outside confidence intervals. Conclusions. Higher complete cytoreduction rate in the PDS group indicates that the correct patients have been selected, but is associated with a higher percentage of complication with re-intervention. As result, time to start adjuvant chemotherapy is longer in this group. Maintaining a balance in aggressiveness of surgery and outcome of the surgical procedure with respect to severe complications is underlined. Bench marked data should be discussed nationally to improve this balance. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).
Published: 2021
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39. Stress Myocardial Perfusion Imaging vs Coronary Computed Tomographic Angiography for Diagnosis of Invasive Vessel-Specific Coronary Physiology: Predictive Modeling Results From the Computed Tomographic Evaluation of Atherosclerotic Determinants of Myocardial Ischemia (CREDENCE) Trial

Author: Alessia Gimelli, Chris J. Rowan, Guus A. de Waard, Gianluca Pontone, Michiel J. Bom, Yao Lu, Faisal Nabi, U. Joseph Schoepf, Roel S. Driessen, Yang Gao, Inge J. van den Hoogen, Sanghoon Shin, James J. Jang, Credence Investigators, Chang-Wook Nam, Hyung-Bok Park, Mouaz H. Al-Mallah, Ryo Nakazato, Jason H. Cole, James K. Min, Leslee J. Shaw, Michael Ridner, Philippe Généreux, Alexander R. van Rosendael, Erick Avelar, Muhammad Akram Khan, Bin Lu, Joon-Hyung Doh, Fay Y. Lin, Bon-Kwon Koo, Wijnand J. Stuijfzand, Randall C. Thompson, Jagat Narula, Jeroen J. Bax, Daniele Andreini, Ae-Young Her, Hyuk Jae Chang, Jung Hyun Choi, Daniel S. Berman, Umberto Gianni, Paul Knaapen, Cardiology, ACS - Atherosclerosis & ischemic syndromes, and ACS - Heart failure & arrhythmias
Subjects: Male, medicine.medical_specialty, Myocardial Ischemia, Fractional flow reserve, 030204 cardiovascular system & hematology, Coronary Angiography, Coronary artery disease, 03 medical and health sciences, Myocardial perfusion imaging, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Aged, Original Investigation, medicine.diagnostic_test, business.industry, Myocardial Perfusion Imaging, Magnetic resonance imaging, Middle Aged, medicine.disease, Prognosis, Plaque, Atherosclerotic, Fractional Flow Reserve, Myocardial, Stenosis, Atheroma, Positron emission tomography, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Tomography, X-Ray Computed, Perfusion
Abstract: Key PointsQuestionAre atherosclerotic plaque measurements associated with physiologic measures of invasive fractional flow reserve? FindingsIn this analysis of the CREDENCE clinical trial that included 612 patients, nonobstructive and obstructive measures of atherosclerotic plaque were significantly associated with invasive fractional flow reserve. A comprehensive set of atherosclerotic plaque features improved the accuracy of classifying vessel-specific reduced fractional flow reserve vs rest/stress myocardial perfusion imaging measurements. MeaningUsing coronary computed tomographic angiography for detection of atherosclerotic plaque features associated with coronary physiology may improve diagnostic certainty and guide clinical management of symptomatic patients.ImportanceStress imaging has been the standard for diagnosing functionally significant coronary artery disease. It is unknown whether novel, atherosclerotic plaque measures improve accuracy beyond coronary stenosis for diagnosing invasive fractional flow reserve (FFR) measurement. ObjectiveTo compare the diagnostic accuracy of comprehensive anatomic (obstructive and nonobstructive atherosclerotic plaque) vs functional imaging measures for estimating vessel-specific FFR. Design, Setting, and ParticipantsControlled clinical trial of diagnostic accuracy with a multicenter derivation-validation cohort of patients referred for nonemergent invasive coronary angiography. A total of 612 patients (64 [10] years; 30% women) with signs and symptoms suggestive of myocardial ischemia from 23 sites were included. Patients were recruited from 2014 to 2017. Data analysis began in August 2018. InterventionsPatients underwent invasive coronary angiography with measurement of invasive FFR, coronary computed tomographic angiography (CCTA) quantification of atherosclerotic plaque and FFR by CT (FFR-CT), and semiquantitative scoring of rest/stress myocardial perfusion imaging (by magnetic resonance, positron emission tomography, or single photon emission CT). Multivariable generalized linear mixed models were derived and validated calculating the area under the receiver operating characteristics curve. Main Outcomes and MeasuresThe primary end point was invasive FFR of 0.80 or less. ResultsOf the 612 patients, the mean (SD) age was 64 (10) years, and 426 (69.9%) were men. An invasive FFR of 0.80 or less was measured in 26.5% of 1727 vessels. In the derivation cohort, CCTA vessel-specific factors associated with FFR 0.80 or less were stenosis severity, percentage of noncalcified atheroma volume, lumen volume, the number of lesions with high-risk plaque (>= 2 of low attenuation plaque, positive remodeling, napkin ring sign, or spotty calcification), and the number of lesions with stenosis greater than 30%. Fractional flow reserve-CT was not additive to this model including stenosis and atherosclerotic plaque. Significant myocardial perfusion imaging predictors were the summed rest and difference scores. In the validation cohort, the areas under the receiver operating characteristic curve were 0.81 for CCTA vs 0.67 for myocardial perfusion imaging (P
Published: 2020
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40. Prevalence of paratuberculosis in dairy cattle in ecuador

Author: Gustavo Echeverr, Henry Escobar, Darwin Changoluisa, Lenin Ron, Andrea Proaño, Freddy Proaño-Pérez, Martin J Zumárraga, and Jacobus H de Waard
Subjects: nontuberculous mycobacteria, lcsh:QR1-502, Enzyme-Linked Immunosorbent Assay, bacterial infections and mycoses, indirect enzyme-linked immunosorbent assay, lcsh:Microbiology, Mycobacterium avium subsp. paratuberculosis, Dairying, Feces, Seroepidemiologic Studies, Paratuberculosis, Prevalence, Animals, Cattle, Female, Ecuador, paratuberculosis or john's disease, polymerase chain reaction-insertion sequence 900
Abstract: Background: Mycobacterium avium subsp. paratuberculosis (MAP) is the causal agent of paratuberculosis, a chronic infectious contagious disease of the intestinal tract of ruminants that are also associated with Crohn's disease in humans. The existence of paratuberculosis in Ecuador is virtually unknown; hence, the present study was performed to gain insight into the prevalence of this disease. Methods: Three dairy cattle farms in different geographic regions in Ecuador were investigated for the infection with MAP, and 600 blood samples, 200 of each cattle herd, were processed with an indirect enzyme-linked immunosorbent assay. Fecal samples of the seropositive cows were processed for culture on modified Löwenstein–Jensen medium. Results: One hundred and fifty bovines (25%) resulted seropositive and we confirmed with culture the presence of MAP in 4.7% (7/150) of the seropositive cows. Approximately 20% of the fecal samples of seropositive cows yielded nontuberculous mycobacteria (NTM) species including M. avium subsp. avium, a NTM species closely related to MAP. Conclusions: The seroprevalence of paratuberculosis in this first study for Ecuador is high (25%). We discuss a possible interference of NTM species, isolated from fecal samples, with the diagnosis of paratuberculosis. With this report, a baseline study, we confirm for the first time the presence of paratuberculosis in Ecuador, and we provide the necessary information for future studies and control of this disease.
Published: 2020

41. Low Risk of Development of a Regional Recurrence After an Unsuccessful Repeat Sentinel Lymph Node Biopsy in Patients with Ipsilateral Breast Tumor Recurrence

Author: Poodt, Ingrid G. M., Walstra, Coco J. E. F., Vugts, Guusje, Maaskant-Braat, Adriana J. G., Voogd, Adri C., Schipper, Robert-Jan, Nieuwenhuijzen, Grard A. P., Roumen, R. M. H., Luiten, E. J. T., Rutgers, E. J. T., Vrancken-Peeters, M. T. F. D., Bessems, M., Klaase, M., Muller, S., Francken, A. B., Van Dalen, T., Jansen, L., Koopal, S. A., Vissers, Y. L. J., Smidt, M. L., Merkus, J. W. S., Contant, C. M. E., Veldman, P. H., Linthorst-Niers, E. M. H., van der Sijp, J. R., Guicherit, O. R., Koppert, L. B., Bosch, A. M., Strobbe, L. J. A., Schlooz-Vries, M. S., Arntz, I. E., van Essen, J. A., de Waard, J. W. D., Vrouenraets, B. C., van Ooijen, B., Developmental Psychology, Surgery, Epidemiologie, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, and MUMC+: MA Heelkunde (9)
Subjects: Adult, medicine.medical_specialty, SURGERY, medicine.medical_treatment, Sentinel lymph node, Regional Disease, Breast Neoplasms, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Biopsy, Medicine, FIBROSIS, Humans, Neoplasm Invasiveness, Aged, Aged, 80 and over, medicine.diagnostic_test, business.industry, Sentinel Lymph Node Biopsy, Axillary Lymph Node Dissection, WOMEN, Sentinel node, Middle Aged, medicine.disease, EUROPEAN INSTITUTE, Prognosis, CANCER, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Radiation therapy, Axilla, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Lymphatic Metastasis, METASTASIS, Lymph Node Excision, 030211 gastroenterology & hepatology, TRIAL, Female, Radiology, Neoplasm Recurrence, Local, Sentinel Lymph Node, business, RADIOTHERAPY, Follow-Up Studies
Abstract: Item does not contain fulltext BACKGROUND: Unlike sentinel lymph node biopsy (SLNB) in the primary setting, the repeat SLNB (rSLNB) in patients with ipsilateral breast tumor recurrence (IBTR) is challenging, because it is difficult to visualize and/or harvest a sentinel lymph node in every patient. Regional treatments options and safety in terms of regional disease control after such an unsuccessful rSLNB remain unclear. This study assesses factors associated with the performance of axillary lymph node dissection (ALND) after unsuccessful rSLNB and evaluates the occurrence of regional recurrences. METHODS: Data were obtained from the Sentinel Node and Recurrent Breast Cancer (SNARB) study. In 239 patients, the rSLNB was unsuccessful, of whom 60 patients underwent ipsilateral ALND. RESULTS: A shorter time interval between primary treatment and IBTR, and a primary negative SLNB were significantly associated with a higher probability to be treated with ALND after unsuccessful rSLNB (P < 0.001). The 5-year regional-recurrence rate was 0.0% in the ALND group compared with 3.7% in the group treated without ALND (P = 0.113). Of the 179 patients treated without ALND, after a median follow-up of 5.1 years (range 0.3-13.2), 7 (3.9%) developed a regional recurrence as first event after unsuccessful rSLNB. None of the seven recurrences occurred in the ipsilateral axilla. Univariable analysis showed no factors associated with regional recurrence as first event after unsuccessful rSLNB (P > 0.05). CONCLUSIONS: The present study demonstrates that the risk of regional recurrence in patients with an IBTR and an unsuccessful rSLNB is negligible, irrespective of the use of ALND. This suggests that there is no need for additional treatment of the axilla after an unsuccessful rSLNB.
Published: 2019

42. Prognostic impact of repeat sentinel lymph node biopsy in patients with ipsilateral breast tumour recurrence

Author: I G M Poodt, G Vugts, R J Schipper, R M H Roumen, H J T Rutten, A J G Maaskant-Braat, A C Voogd, G A P Nieuwenhuijzen, E J T Luiten, E J T Rutgers, M T F D Vrancken-Peeters, M Bessems, J M Klaase, S Muller, A B Francken, T Van Dalen, L Jansen, S A Koopal, Y L J Vissers, M L Smidt, J W S Merkus, C M E Contant, P H Veldman, E M H Linthorst-Niers, J R van der Sijp, O R Guicherit, L B Koppert, A M Bosch, L J A Strobbe, M S Schlooz-Vries, I E Arntz, J A van Essen, J W D de Waard, B C Vrouenraets, B van Ooijen, Surgery, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, and Epidemiologie
Subjects: Oncology, Adult, medicine.medical_specialty, Time Factors, SURGERY, Sentinel lymph node, Breast Neoplasms, LOCAL RECURRENCE, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Internal medicine, CONSERVING THERAPY, Biopsy, Medicine, Humans, FAILURE, In patient, Neoplasm Metastasis, Survival rate, SURGICAL ADJUVANT BREAST, METAANALYSIS, Aged, LOCOREGIONAL RECURRENCES, medicine.diagnostic_test, business.industry, Proportional hazards model, Sentinel Lymph Node Biopsy, Sentinel node, Middle Aged, medicine.disease, Prognosis, CANCER, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], 030220 oncology & carcinogenesis, Ipsilateral breast, PATTERNS, 030211 gastroenterology & hepatology, Female, CONSERVATION THERAPY, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract: Background Ipsilateral breast tumour recurrence (IBTR) has an unfavourable prognosis, with a significant subsequent risk of distant recurrence. Repeat sentinel lymph node biopsy (rSLNB) has recently been demonstrated to be technically feasible and useful in tailoring adjuvant treatment plans in patients with IBTR. The prognostic impact of rSLNB in patients with IBTR remains unclear. This study analysed the risk of distant recurrence after IBTR, and evaluated the prognostic impact of rSLNB and other patient and tumour characteristics on distant recurrence-free survival. Methods Data were obtained from the SNARB (Sentinel Node and Recurrent Breast Cancer) study. Cox proportional hazards analyses were performed to assess the prognostic effect of tumour, patient and treatment factors on distant recurrence-free survival. Results Of the 515 included patients, 230 (44·7 per cent) had a tumour-negative rSLNB and 46 (8·9 per cent) a tumour-positive rSLNB. In 239 patients (46·4 per cent) the rSLNB procedure was unsuccessful. After a median follow-up of 5·1 years, 115 patients (22·3 per cent) had developed a recurrence. The overall 5-year distant recurrence-free survival rate was 84·2 (95 per cent c.i. 80·7 to 87·7) per cent. An interval of less than 2 years between primary breast cancer treatment and ipsilateral recurrence (P = 0·018), triple-negative IBTR (P = 0·045) and absence of adjuvant chemotherapy after IBTR (P = 0·010) were independently associated with poor distant recurrence-free survival. The association between the outcome of rSLNB and distant recurrence-free survival was not statistically significant (P = 0·682). Conclusion The outcome of rSLNB is not an important prognostic factor for distant recurrence, and its value as a staging tool in patients with IBTR seems disputable.
Published: 2019
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43. Nutrition During Pregnancy, Lactation and Early Childhood and its Implications for Maternal and Long-Term Child Health

Author: Koletzko, B, Godfrey, KM, Poston, L, Szajewska, H, van Goudoever, JB, de Waard, M, Brands, B, Grivell, RM, Deussen, AR, Dodd, JM, Patro-Golab, B, Zalewski, BM, Alberdi, G, Buonocore, G, Campoy, C, Demmelmair, H, Desoye, G, Gomez, MD, Escribano, J, Geraghty, A, Gil, A, Hanson, M, Inskip, HM, Larque, E, Lassel, T, Luque, V, Mader, S, Manios, Y, Mearin, LM, Oddy, WH, Reynolds, RM, Rueda, R, Sherry, C, Socha, P, Taylor, P, Van der Beek, EM, Weber, M, Crespo-Escobar, P, Gutser, M, Kouwenhoven, SMP, Calvo-Lerma, J, Veldhorst, M, and EarlyNutr Project Systematic Revie
Subjects: 0301 basic medicine, Gerontology, Infancy, PROTEIN-INTAKE, Maternal Health, Breastfeeding, Medicine (miscellaneous), Disease, Overweight, Recommendations, Nutrition Policy, 0302 clinical medicine, Pregnancy, FORMULA-FED INFANTS, AGE FOLLOW-UP, Medicine, Early childhood, Micronutrients, Infant Nutritional Physiological Phenomena, Prenatal Nutritional Physiological Phenomena, media_common, 2. Zero hunger, Child health, GESTATIONAL WEIGHT-GAIN, Nutrition and Dietetics, Preconception, 3. Good health, Systematic review, Breast Feeding, Child, Preschool, Female, LIFE-STYLE, medicine.symptom, VITAMIN-D DEFICIENCY, YOUNG-CHILDREN, 030209 endocrinology & metabolism, Early nutrition, Developmental programming, 03 medical and health sciences, Metabolic programming, media_common.cataloged_instance, Humans, Lactation, Obesity, European union, Life Style, 030109 nutrition & dietetics, business.industry, Infant, medicine.disease, Lifestyle, PERICONCEPTIONAL FOLIC-ACID, BODY-MASS INDEX, BREAST-FED INFANTS, business, Systematic Reviews as Topic
Abstract: Background: A considerable body of evidence accumulated especially during the last decade, demonstrating that early nutrition and lifestyle have long-term effects on later health and disease (“developmental or metabolic programming”). Methods: Researchers involved in the European Union funded international EarlyNutrition research project consolidated the scientific evidence base and existing recommendations to formulate consensus recommendations on nutrition and lifestyle before and during pregnancy, during infancy and early childhood that take long-term health impact into account. Systematic reviews were performed on published dietary guidelines, standards and recommendations, with special attention to long-term health consequences. In addition, systematic reviews of published systematic reviews on nutritional interventions or exposures in pregnancy and in infants and young children aged up to 3 years that describe effects on subsequent overweight, obesity and body composition were performed. Experts developed consensus recommendations incorporating the wide-ranging expertise from additional 33 stakeholders. Findings: Most current recommendations for pregnant women, particularly obese women, and for young children do not take long-term health consequences of early nutrition into account, although the available evidence for relevant consequences of lifestyle, diet and growth patterns in early life on later health and disease risk is strong. Interpretation: We present updated recommendations for optimized nutrition before and during pregnancy, during lactation, infancy and toddlerhood, with special reference to later health outcomes. These recommendations are developed for affluent populations, such as women and children in Europe, and should contribute to the primary prevention of obesity and associated non-communicable diseases.
Published: 2019
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44. Temporal Changes in Coronary Hyperemic and Resting Hemodynamic Indices in Nonculprit Vessels of Patients With ST-Segment Elevation Myocardial Infarction

Author: Ricardo Petraco, Maarten A.H. van Leeuwen, Justin E. Davies, Gladys N. Janssens, Nina W. van der Hoeven, Henk Everaars, Javier Escaned, Guus A. de Waard, Niels van Royen, Peter M. van de Ven, Robin Nijveldt, Casper W.H. Beijnink, Christopher Cook, Tim ten Cate, Clemens von Birgelen, Christopher Broyd, Health Technology & Services Research, Academic Medical Center, Cardiology, ACS - Atherosclerosis & ischemic syndromes, APH - Methodology, ACS - Heart failure & arrhythmias, and Epidemiology and Data Science
Subjects: Male, medicine.medical_specialty, Time Factors, medicine.medical_treatment, Rest, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Hemodynamics, Hyperemia, Fractional flow reserve, 030204 cardiovascular system & hematology, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, Myocardial infarction, Instantaneous wave-free ratio, Aged, business.industry, Microcirculation, Coronary Stenosis, Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16], Coronary flow reserve, Percutaneous coronary intervention, Middle Aged, medicine.disease, Coronary Vessels, n/a OA procedure, Conventional PCI, Aortic pressure, Cardiology, ST Elevation Myocardial Infarction, Female, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies
Abstract: Importance: Percutaneous coronary intervention (PCI) of nonculprit vessels among patients with ST-segment elevation myocardial infarction (STEMI) is associated with improved clinical outcome compared with culprit vessel-only PCI. Fractional flow reserve (FFR) and coronary flow reserve are hyperemic indices used to guide revascularization. Recently, instantaneous wave-free ratio was introduced as a nonhyperemic alternative to FFR. Whether these indices can be used in the acute setting of STEMI continues to be investigated. Objective: To assess the value of hemodynamic indices in nonculprit vessels of patients with STEMI from the index event to 1-month follow-up. Design, Setting, and Participants: This substudy of the Reducing Micro Vascular Dysfunction in Revascularized STEMI Patients by Off-target Properties of Ticagrelor (REDUCE-MVI) randomized clinical trial enrolled 98 patients with STEMI who had an angiographic intermediate stenosis in at least 1 nonculprit vessel. Patient enrollment was between May 1, 2015, and September 19, 2017. After successful primary PCI, nonculprit intracoronary hemodynamic measurements were performed and repeated at 1-month follow-up. Cardiac magnetic resonance imaging was performed from 2 to 7 days and 1 month after primary PCI. Main Outcomes and Measures: The value of nonculprit instantaneous wave-free ratio, FFR, coronary flow reserve, hyperemic index of microcirculatory resistance, and resting microcirculatory resistance from the index event to 1-month follow-up. Results: Of 73 patients with STEMI included in the final analysis, 59 (80.8%) were male, with a mean (SD) age of 60.8 (9.9) years. Instantaneous wave-free ratio (SD) did not change significantly (0.93 [0.07] vs 0.94 [0.06]; P =.12) and there was no change in resting distal pressure/aortic pressure (mean [SD], 0.94 [0.06] vs 0.95 [0.06]; P =.25) from the acute moment to 1-month follow-up. The FFR decreased (mean [SD], 0.88 [0.07] vs 0.86 [0.09]; P =.001) whereas coronary flow reserve increased (mean [SD], 2.9 [1.4] vs 4.1 [2.2]; P
Published: 2019
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45. Medication Use During Pregnancy and Lactation in a Dutch Population

Author: Marinka L.F. Hol, Willemijn E. Corpeleijn, Birgit S Blomjous, Johannes B. van Goudoever, Marita de Waard, Mirjam M. van Weissenbruch, Sintha D. Sie, Pediatric surgery, Amsterdam Reproduction & Development (AR&D), Obstetrics and gynaecology, Rheumatology, ACS - Atherosclerosis & ischemic syndromes, ACS - Pulmonary hypertension & thrombosis, VU University medical center, AGEM - Endocrinology, metabolism and nutrition, ACS - Diabetes & metabolism, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, NCA - Neurobiology of mental health, MKA AMC (ORM, ACTA), General Paediatrics, Oral and Maxillofacial Surgery, Graduate School, AR&D - Amsterdam Reproduction & Development, Neonatology, and Maxillofacial Surgery (AMC)
Subjects: Adult, Pediatrics, medicine.medical_specialty, Breastfeeding, Interviews as Topic, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Pregnancy, Surveys and Questionnaires, 030225 pediatrics, Lactation, Prevalence, medicine, Humans, 030212 general & internal medicine, Netherlands, Medication use, business.industry, Postpartum Period, Infant, Newborn, Abnormalities, Drug-Induced, Obstetrics and Gynecology, Prenatal Care, medicine.disease, Breast Feeding, Cross-Sectional Studies, medicine.anatomical_structure, Pharmaceutical Preparations, Dutch Population, Structured interview, Female, business, Risk classification, Healthcare providers
Abstract: Background: Medication use during pregnancy and lactation can be unavoidable, but knowledge on safety for the fetus or breastfed infant is limited among patients and healthcare providers. Research aim: This study aimed to determine (a) the prevalence of medication use in pregnant and lactating women in a tertiary academic center, (b) the types and safety of these medicines, and (c) the influence of medication use on initiation of breastfeeding. Methods: This study used a cross-sectional survey among women ( N = 292) who underwent high-risk or low-risk deliveries. Data about their use of prescribed, over-the-counter, and homeopathic medication during pregnancy were obtained through a structured interview, followed by a questionnaire during lactation. Safety was classified according to the risk classification system from the Dutch Teratological Information Service. Results: Overall, 95.5% of participants used medication. One third of participants used at least one medicine with an unknown risk for the fetus. Teratogenic medication was used by 6.5% of participants, whereas 29.5% used medication with a (suspected) pharmacological effect on the fetus. Lactation was initiated by 258 (88.7%) participants, of which 84.2% used medication while breastfeeding. In 3.8% of participants, this medication was classified unsafe, but none used medication with an unknown risk. One-third of the nonlactating participants decided not to initiate breastfeeding because of medication use. In 70% of participants, this decision was appropriate. Conclusion: The prevalence of overall use of medication in Dutch pregnant and lactating women admitted to a tertiary center was high. There is an urgent need for pharmacometric studies for determination of the safe use of the most frequently used medicines during pregnancy or lactation.
Published: 2019
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46. Cycling on the edge: the effects of edge lines, slanted kerbstones, shoulder, and edge strips on cycling behaviour of cyclists older than 50 years

Author: Frank Westerhuis, Anselm B. M. Fuermaier, Dick de Waard, Karel Brookhuis, and Clinical Neuropsychology
Subjects: safety, LANE, Male, medicine.medical_specialty, Injury control, Accident prevention, Shoulders, Poison control, Physical Therapy, Sports Therapy and Rehabilitation, Human Factors and Ergonomics, STRIPS, Edge (geometry), E-BIKES, law.invention, ROAD, Physical medicine and rehabilitation, Accident Prevention, law, medicine, Humans, line marking, SPEED, Aged, Aged, 80 and over, CONVENTIONAL BICYCLE, business.industry, WIDTH, PERFORMANCE, Middle Aged, shoulders, Bicycling, ageing, Environment Design, Female, RUMBLE STRIPS, Cycling, business
Abstract: To prevent single-bicycle crashes, this study is the first to evaluate effects of slanted kerbstones, edge lines, shoulder strips, and edge strips on cycling behaviour of cyclists ≥50 years. In Experiment 1, 32 participants cycled on a control path and paths with edge lines, slanted kerbstones, and three types of 0.5 m wide shoulder strips (with grey artificial grass, green artificial grass, or concrete street-print). In Experiment 2, 30 participants cycled a different route including a control path and paths with edge lines or 0.3 m white edge strips. Cyclists rode closer to the main cycle path’s edge in the shoulder strips conditions, although the presence of these strips resulted in a larger total distance to the verge compared to the control condition. Furthermore, cyclists cycled further from the verge in the edge strip condition than the control condition. Safety implications of the shoulder and edge strips are considered to be positive. Practitioner Summary: Older cyclists have a high risk for single-bicycle crashes (e.g. riding into the verge). In two experiments, cyclists ≥50 years cycled a route where different treatments were applied on a cycle path. Shoulder and edge strip treatments were related to more efficient path use and safer distances from the verge. Abbreviations: AGS: artificial grass strip; CL: control location; CSS: concrete street-print strip; ELC: edge line continuous; ELI: edge line intermittent; LP: lateral position; SDLP: standard deviation of the lateral position; SK: slanted kerbstones; WCES: white chippings edge strip.
Published: 2020

47. Odontogenic cutaneous sinus tracts due to infection with nontuberculous mycobacteria: a report of three cases

Author: Ricardo Pérez-Alfonzo, Carolina Carrera Martinez, Perla Luiguimar Meneses Rodríguez, Carmen Elena Kannee Quintero, Luisa Elena Poleo Brito, Marialejandra Solano Vergara, Jacobus H. de Waard, Ismar Alejandra Rivera-Oliver, Angela Ruiz Damasco, Bárbara A. Rodríguez-Castillo, and Omaira Da Mata Jardín
Subjects: 0301 basic medicine, medicine.medical_specialty, Adolescent, 030106 microbiology, Dental unit waterline (DUWL), Mycobacterium peregrinum, Mycobacterium Infections, Nontuberculous, Case Report, Skin infection, Mycobacterium abscessus, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Medical microbiology, medicine, Humans, lcsh:RC109-216, 030212 general & internal medicine, Child, Dental Procedure, Sinus (anatomy), biology, business.industry, Soft tissue infection, Mycobacterium fortuitum, Fungi, Nontuberculous Mycobacteria, medicine.disease, biology.organism_classification, bacterial infections and mycoses, Dermatology, Infectious Diseases, medicine.anatomical_structure, Nontuberculous mycobacteria (NTM), Face, DNA, Viral, Nontuberculous mycobacteria, Female, business, Water Microbiology, Cutaneous sinus tract
Abstract: Background Soft tissue or skin infections due to nontuberculous mycobacteria (NTM) have been reported frequently and are mostly associated with trauma or cosmetic interventions like plastic surgery. However, infection with NTM as a result of a dental procedure have rarely been described and the lack of clinical suspicion and a clear clinical manifestation makes diagnosis challenging. Case presentation We report on three patients with a facial cutaneous sinus tract of dental origin, due to an infection with respectively Mycobacterium fortuitum, M. abscessus and M. peregrinum. The infection source was the dental unit waterlines (DUWLs), which were colonized with NTM. Conclusions Water of the DUWL can pose a health risk. This report emphasizes the need for quality control and certification of water flowing through DUWLs, including the absence of NTM. Our report also shows the need for a rapid recognition of NTM infections and accurate laboratory diagnosis in order to avoid long-term ineffective antibiotic treatment.
Published: 2020

48. Essential diseases in prescribing: A national Delphi study towards a core curriculum in pharmacotherapy education

Author: M.A. van Agtmael, Milan C. Richir, B. Jansen, B.H.E. Jansen, A. M. Vondeling, G. W. Disselhorst, Jelle Tichelaar, Robert Rissmann, Floris Vanmolkot, A. Maassen van den Brink, Tim Schutte, Glenn Dumont, Cornelis Kramers, I. de Waard-Siebinga, Carolina J. P. W. Keijsers, Internal Medicine, Interne Geneeskunde, MUMC+: MA Alg Interne Geneeskunde (9), RS: FHML non-thematic output, Internal medicine, Urology, VU University medical center, General practice, and Other Research
Subjects: Adult, Male, MEDICAL-STUDENTS, Consensus, Delphi Technique, education, Delphi method, Disease, DOCTORS, 030226 pharmacology & pharmacy, Likert scale, law.invention, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], 03 medical and health sciences, pharmacotherapy, 0302 clinical medicine, Pharmacotherapy, All institutes and research themes of the Radboud University Medical Center, Drug Therapy, law, Surveys and Questionnaires, Medical Staff, Hospital, Humans, Pharmacology (medical), 030212 general & internal medicine, Medical prescription, Practice Patterns, Physicians', Competence (human resources), computer.programming_language, Netherlands, Pharmacology, Medical education, Clinical pharmacology, Education, Medical, prescribing, VIEWS, Original Articles, CLINICAL-PHARMACOLOGY, Female, Clinical Competence, Curriculum, Psychology, medical education, computer, Delphi
Abstract: AimsPrescribing is a core skill for junior doctors, yet 8-10% of their prescriptions contain errors. To ensure adequate training in prescribing, it is important to define the diseases for which junior doctors should be competent to prescribe. The aim of the present study was therefore to identify the essential diseases in prescribing for junior doctors.MethodsA two-round Delphi consensus study was conducted among medical specialists, general practitioners, junior doctors, pharmacists and pharmacotherapy teachers from all eight academic hospitals in the Netherlands. Using a five-point Likert scale, the participants indicated for each item on an initial questionnaire whether it should be considered an essential disease for junior doctors. The items for which 80% of all respondents agreed or strongly agreed were accepted as essential diseases.ResultsSixty-two participants completed the Delphi survey. In total, 63 of 220 items were considered to be essential diseases.ConclusionThis is the first Delphi consensus study identifying exact conditions that junior doctors must be able to prescribe for. The essential diseases can be used for training in prescribing and assessment of junior doctors' prescribing competence.
Published: 2018
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49. Anticancer properties of lipid and poly(ε-caprolactone) nanocapsules loaded with ferrocenyl-tamoxifen derivatives

Author: Lucie Sancey, Benoit Busser, Mylène Pezet, Stéphane Gibaud, Ali Rhouma, Gérard Jaouen, Pascal Pigeon, Naziha Marrakchi, Sonia Aroui, Feten Najlaoui, Michel De Waard, Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Cibles thérapeutiques, formulation et expertise pré-clinique du médicament (CITHEFOR), Université de Lorraine (UL), Institut Parisien de Chimie Moléculaire (IPCM), Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL), Chemical Biology (CHEMBIO), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Chimie Moléculaire de Paris Centre (FR 2769), Université de Monastir - University of Monastir (UM), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire des Venins et Biomolécules Thérapeutiques - Laboratory of Venoms and Therapeutic Biomolecules (LR11IPT08), Olive Tree Institute, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Chemistry, Pharmaceutical, Pharmaceutical Science, Apoptosis, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 02 engineering and technology, Pharmacology, 01 natural sciences, Lipid nanocapsules, chemistry.chemical_compound, Drug Carriers, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Brain Neoplasms, Chemistry, Cell Cycle, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Prodrug, 021001 nanoscience & nanotechnology, Lipids, 3. Good health, Female, 0210 nano-technology, Caprolactone, medicine.drug, Drug Compounding, Polyesters, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antineoplastic Agents, Breast Neoplasms, 010402 general chemistry, Nanocapsules, ferrocenyl-tamoxifen derivatives, breast cancer, Cell Line, Tumor, polymer nanocapsules, medicine, Animals, Humans, [CHIM.COOR]Chemical Sciences/Coordination chemistry, IC50, Cell Proliferation, Rats, Inbred F344, In vitro, 0104 chemical sciences, Drug Liberation, Kinetics, Tamoxifen, Solubility, Cancer cell, Nanocarriers, Glioblastoma
Abstract: Objective We synthesized new tamoxifen derivatives as anticancer drug candidates and elaborated on convection-enhanced delivery (CED) as a strategy for delivery. Methods To overcome the issue of their poor solubility, these ferrocenyl-tamoxifen derivatives were esterified and encapsulated into different nanocarriers, that is lipid (LNC) and polymeric nanocapsules (PNL-NC). We describe the chemistry, the encapsulation and the physicochemical characterization of these formulations. Key findings Starting compounds [phthalimido-ferrocidiphenol and succinimido-ferrocidiphenol], esterified prodrugs and their nanocapsules formulations were characterized. These drug candidates displayed a strong in vitro activity against breast and glioblastoma cancer cells. The ester prodrugs were toxic for glioblastoma cells (IC50 = 9.2 × 10−2 μm and 6.7 × 10−2 μm, respectively). The IC50 values for breast cancer cells were higher for these compounds. The encapsulation of the esterified compounds in LNCs (≈50 nm) or PCL-NCs (≈300 nm) did not prevent their efficacy on glioblastoma cells. These anticancer effects were due to both blockade in the S-phase of the cell cycle and apoptosis. Moreover, the tamoxifen derivatives-loaded nanocapsules induced no toxicity for healthy astrocytes and showed no haemolytic properties. Loaded Lipid Nanocapsules (LNCs) presented interesting profiles for the optimal delivery of active compounds. Conclusions Phthalimido- and Succinimido-esters represent an innovative approach to treat cancers with cerebral localizations such as glioblastoma or brain metastases from breast cancers.
Published: 2018
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50. Primary Baerveldt versus trabeculectomy study after one-year follow-up

Author: Esma Islamaj, Peter W.T. de Waard, and René J Wubbels
Subjects: Adult, Male, Intraocular pressure, medicine.medical_specialty, Time Factors, Visual acuity, Adolescent, genetic structures, medicine.medical_treatment, Visual Acuity, Glaucoma, Trabeculectomy, Prosthesis Design, Young Adult, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, medicine, Humans, Prospective Studies, Glaucoma Drainage Implants, Prospective cohort study, Intraocular Pressure, Aged, Netherlands, Diplopia, Glaucoma medication, business.industry, General Medicine, Middle Aged, medicine.disease, eye diseases, Surgery, Ophthalmology, Treatment Outcome, 030221 ophthalmology & optometry, Female, sense organs, Implant, medicine.symptom, business, Sclera, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: PURPOSE Although the Baerveldt glaucoma implant (BGI) initially was reserved for refractory glaucoma, its role in the surgical management of glaucoma has shifted towards a primary treatment choice. We performed a randomized prospective study to compare BGI surgery and trabeculectomy (TE) in patients without previous ocular surgery. METHODS We included 119 glaucoma patients without previous ocular surgery. One eye of each subject was randomized to either a BGI or TE. Follow-up visits were at 1 day, 2 weeks, 6 weeks, 3 months, 6 months and 1, 2, 3, 4 and 5 years postoperatively. Primary outcomes were intraocular pressure (IOP) and failure rate. Secondary outcomes were medication, anterior chamber laser flare value and complications. RESULTS After 5 years, an IOP of 12.7 ± 3.9 mmHg (mean ± SD) was achieved in the TE group and 12.9 ± 3.9 mmHg in the BGI group. We found no statistically significant difference in failure rate between the groups (p = 0.72). More BGI patients needed additional medication to control their IOP (85%; 1.9 ± 1.2 types of glaucoma medication) compared to the TE patients (57%; 0.5 ± 0.9 types of glaucoma medication). Diplopia was significantly more present in the BGI group than in the TE group (27% versus 4%; p
Published: 2018
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