Author: "Martijn Beudel" - Searchworks@Jio Institute Digital Library Search Results

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1. Sensing data and methodology from the Adaptive DBS Algorithm for Personalized Therapy in Parkinson’s Disease (ADAPT-PD) clinical trial

Author: Scott Stanslaski, Rebekah L. S. Summers, Lisa Tonder, Ye Tan, Michelle Case, Robert S. Raike, Nathan Morelli, Todd M. Herrington, Martijn Beudel, Jill L. Ostrem, Simon Little, Leonardo Almeida, Adolfo Ramirez-Zamora, Alfonso Fasano, Travis Hassell, Kyle T. Mitchell, Elena Moro, Michal Gostkowski, Nagaraja Sarangmat, Helen Bronte-Stewart, and On behalf of the ADAPT-PD Investigators
Subjects: Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Adaptive deep brain stimulation (aDBS) is an emerging advancement in DBS technology; however, local field potential (LFP) signal rate detection sufficient for aDBS algorithms and the methods to set-up aDBS have yet to be defined. Here we summarize sensing data and aDBS programming steps associated with the ongoing Adaptive DBS Algorithm for Personalized Therapy in Parkinson’s Disease (ADAPT-PD) pivotal trial (NCT04547712). Sixty-eight patients were enrolled with either subthalamic nucleus or globus pallidus internus DBS leads connected to a Medtronic PerceptTM PC neurostimulator. During the enrollment and screening procedures, a LFP (8–30 Hz, ≥1.2 µVp) control signal was identified by clinicians in 84.8% of patients on medication (65% bilateral signal), and in 92% of patients off medication (78% bilateral signal). The ADAPT-PD trial sensing data indicate a high LFP signal presence in both on and off medication states of these patients, with bilateral signal in the majority, regardless of PD phenotype.
Published: 2024
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2. Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection

Author: Astrid Marchal, Elizabeth T. Cirulli, Iva Neveux, Evangelos Bellos, Ryan S. Thwaites, Kelly M. Schiabor Barrett, Yu Zhang, Ivana Nemes-Bokun, Mariya Kalinova, Andrew Catchpole, Stuart G. Tangye, András N. Spaan, Justin B. Lack, Jade Ghosn, Charles Burdet, Guy Gorochov, Florence Tubach, Pierre Hausfater, Clifton L. Dalgard, Shen-Ying Zhang, Qian Zhang, Christopher Chiu, Jacques Fellay, Joseph J. Grzymski, Vanessa Sancho-Shimizu, Laurent Abel, Jean-Laurent Casanova, Aurélie Cobat, Alexandre Bolze, Alessandro Aiuti, Saleh Al-Muhsen, Fahd Al-Mulla, Ali Amara, Mark S. Anderson, Evangelos Andreakos, Andrés A. Arias, Lisa M. Arkin, Hagit Baris Feldman, Paul Bastard, Alexandre Belot, Catherine M. Biggs, Dusan Bogunovic, Anastasiia Bondarenko, Alessandro Borghesi, Ahmed A. Bousfiha, Petter Brodin, Yenan Bryceson, Manish J. Butte, Giorgio Casari, John Christodoulou, Roger Colobran, Antonio Condino-Neto, Stefan N. Constantinescu, Megan A. Cooper, Murkesh Desai, Beth A. Drolet, Xavier Duval, Jamila El Baghdadi, Philippine Eloy, Sara Espinosa-Padilla, Carlos Flores, José Luis Franco, Antoine Froidure, Peter K. Gregersen, Bodo Grimbacher, Filomeen Haerynck, David Hagin, Rabih Halwani, Lennart Hammarström, James R. Heath, Elena W.Y. Hsieh, Eystein Husebye, Kohsuke Imai, Yuval Itan, Emmanuelle Jouanguy, Elżbieta Kaja, Timokratis Karamitros, Kai Kisand, Cheng-Lung Ku, Yu-Lung Lau, Yun Ling, Carrie L. Lucas, Tom Maniatis, Davood Mansouri, László Maródi, France Mentré, Isabelle Meyts, Joshua D. Milner, Kristina Mironska, Trine H. Mogensen, Tomohiro Morio, Lisa F.P. Ng, Luigi D. Notarangelo, Antonio Novelli, Giuseppe Novelli, Cliona O'Farrelly, Satoshi Okada, Keisuke Okamoto, Tayfun Ozcelik, Qiang Pan-Hammarström, Jean W. Pape, Rebeca Perez de Diego, Jordi Perez-Tur, David S. Perlin, Graziano Pesole, Anna M. Planas, Carolina Prando, Aurora Pujol, Anne Puel, Lluis Quintana-Murci, Sathishkumar Ramaswamy, Laurent Renia, Igor Resnick, Carlos Rodríguez-Gallego, Anna Sediva, Mikko R.J. Seppänen, Mohammad Shahrooei, Anna Shcherbina, Ondrej Slaby, Andrew L. Snow, Pere Soler-Palacín, Vassili Soumelis, Ivan Tancevski, Ahmad Abou Tayoun, Şehime Gülsün Temel, Christian Thorball, Pierre Tiberghien, Sophie Trouillet-Assant, Stuart E. Turvey, K. M. Furkan Uddin, Mohammed J. Uddin, Diederik van de Beek, Donald C. Vinh, Horst von Bernuth, Joost Wauters, Mayana Zatz, Pawel Zawadzki, Serge Bureau, Yannick Vacher, Anne Gysembergh-Houal, Lauren Demerville, Abla Benleulmi-Chaachoua, Sebastien Abad, Radhiya Abassi, Abdelrafie Abdellaoui, Abdelkrim Abdelmalek, Hendy Abdoul, Helene Abergel, Fariza Abeud, Sophie Abgrall, Noemie Abisror, Marylise Adechian, Nordine Aderdour, Hakeem Farid Admane, Frederic Adnet, Sara Afritt, Helene Agostini, Claire Aguilar, Sophie Agut, Tommaso Francesco Aiello, Marc Ait Kaci, Hafid Ait Oufella, Gokula Ajeenthiravasan, Virginie Alauzy, Fanny Alby-Laurent, Lucie Allard, Marie-Alexandra Alyanakian, Blanca Amador Borrero, Sabrina Amam, Lucile Amrouche, Marc Andronikof, Dany Anglicheau, Nadia Anguel, Djillali Annane, Mohammed Aounzou, Caroline Aparicio, Gladys Aratus, Jean-Benoit Arlet, Jeremy Arzoine, Elisabeth Aslangul, Mona Assefi, Adeline Aubry, Laetitia Audiffred, Etienne Audureau, Christelle Nathalie Auger, Jean-Charles Auregan, Celine Awotar, Sonia Ayllon Milla, Delphine Azan, Laurene Azemar, Billal Azzouguen, Marwa Bachir Elrufaai, Aïda Badsi, Prissile Bakouboula, Coline Balcerowiak, Fanta Balde, Elodie Baldivia, Eliane-Flore Bangamingo, Amandine Baptiste, Fanny Baran-Marszak, Caroline Barau, Nathalie Barget, Flore Baronnet, Romain Barthelemy, Jean-Luc Baudel, Camille Baudry, Elodie Baudry, Laurent Beaugerie, Adel Belamri, Nicolas Belaube, Rhida Belilita, Pierre Bellassen, Rawan Belmokhtar, Isabel Beltran, Ruben Benainous, Mourad Benallaoua, Robert Benamouzig, Amélie Benbara, Jaouad Benhida, Anis Benkhelouf, Jihene Benlagha, Chahinez Benmostafa, Skander Benothmane, Miassa Bentifraouine, Laurence Berard, Quentin Bernier, Enora Berti, Astrid Bertier, Laure Berton, Simon Bessis, Alexandra Beurton, Celine Bianco, Clara Bianquis, Frank Bidar, Philippe Blanche, Clarisse Blayau, Alexandre Bleibtreu, Emmanuelle Blin, Coralie Bloch-Queyrat, Marie-Christophe Boissier, Diane Bollens, Marion Bolzoni, Rudy pierre Bompard, Nicolas Bonnet, Justine Bonnouvrier, Shirmonecrystal Botha, Wissam Boucenna, Fatiha Bouchama, Olivier Bouchaud, Hanane Bouchghoul, Taoueslylia Boudjebla, Noel Boudjema, Catherine Bouffard, Adrien Bougle, Meriem Bouguerra, Leila Bouras, Agnes Bourcier, Anne Bourgarit Durand, Anne Bourrier, Fabrice Bouscarat, Diane Bouvry, Nesrine Bouziri, Ons Bouzrara, Sarah Bribier, Delphine Brugier, Melanie Brunel, Eida Bui, Anne Buisson, Iryna Bukreyeva, Côme Bureau, Jacques Cadranel, Johann Cailhol, Ruxandra Calin, Clara Campos Vega, Pauline Canavaggio, Marta Cancella, Delphine Cantin, Albert Cao, Lionel Carbillon, Nicolas Carlier, Clementine Cassard, Guylaine Castor, Marion Cauchy, Olivier Cha, Benjamin Chaigne, Salima Challal, Karine Champion, Patrick Chariot, Julie Chas, Simon Chauveau, Anthony Chauvin, Clement Chauvin, Nathalie Chavarot, Kamélia Chebbout, Mustapha Cherai, Ilaria Cherubini, Amelie Chevalier, Thibault Chiarabini, Thierry Chinet, Richard Chocron, Pascaline Choinier, Juliette Chommeloux, Christophe Choquet, Laure Choupeaux, Benjamin Chousterman, Dragosmarius Ciocan, Ada Clarke, Gaëlle Clavere, Florian Clavier, Karine Clement, Sebastien Clerc, Yves Cohen, Fleur Cohen, Adrien Cohen, Audrey Coilly, Hester Colboc, Pauline Colin, Magalie Collet, Chloé Comarmond, Emeline Combacon, Alain Combes, Celine Comparon, Jean-Michel Constantin, Hugues Cordel, Anne-Gael Cordier, Adrien Costantini, Nathalie Costedoat Chalumeau, Camille Couffignal, Doriane Coupeau, Alain Creange, Yannie Cuvillier Lamarre, Charlène Da Silveira, Sandrine Dautheville Guibal El Kayani, Nathalie De Castro, Yann De Rycke, Lucie Del Pozo, Quentin Delannoy, Mathieu Delay, Robin Deleris, Juliette Delforge, Laëtitia Delphine, Noemie Demare, Sophie Demeret, Alexandre Demoule, Aurore Deniau, François Depret, Sophie Derolez, Ouda Derradji, Nawal Derridj, Vincent Descamps, Lydia Deschamps, Celine Desconclois, Cyrielle Desnos, Karine Desongins, Robin Dhote, Benjamin Diallo, Morgane Didier, Myriam Diemer, Stephane Diez, Juliette Djadi-Prat, Fatima-Zohra Djamouri Monnory, Siham Djebara, Naoual Djebra, Minette Djietcheu, Hadjer Djillali, Nouara Djouadi, Severine Donneger, Catarina Dos Santos, Nathalie Dournon, Martin Dres, Laura Droctove, Marie Drogrey, Margot Dropy, Elodie Drouet, Valérie Dubosq, Evelyne Dubreucq, Estelle Dubus, Boris Duchemann, Thibault Duchenoy, Emmanuel Dudoignon, Romain Dufau, Florence Dumas, Clara Duran, Emmanuelle Duron, Antoine Durrbach, Claudine Duvivier, Nathan Ebstein, Jihane El Khalifa, Alexandre Elabbadi, Caroline Elie, Gabriel Ernotte, Anne Esling, Martin Etienne, Xavier Eyer, Muriel Sarah Fartoukh, Takoua Fayali, Marion Fermaut, Arianna Fiorentino, Souha Fliss, Marie-Céline Fournier, Benjamin Fournier, Hélène Francois, Olivia Freynet, Yvann Frigout, Isaure Fromont, Axelle Fuentes, Thomas Furet, Joris Galand, Marc Garnier, Agnes Gaubert, Stéphane Gaudry, Samuel Gaugain, Damien Gauthier, Maxime Gautier, Sophie Georgin-Lavialle, Daniela Geromin, Mohamed Ghalayini, Bijan Ghaleh, Myriam Ghezal, Aude Gibelin, Linda Gimeno, Benoit Girard, Bénédicte Giroux Leprieur, Doryan Gomes, Elisabete Gomes-Pires, Anne Gouge, Amel Gouja, Helene Goulet, Sylvain Goupil, Jeanne Goupil De Bouille, Julien Gras, Segolene Greffe, Lamiae Grimaldi, Paul Guedeney, Bertrand Guidet, Matthias Guillo, Mariechristelle Gulczynski, Tassadit Hadjam, Didier Haguenauer, Soumeya Hammal, Nadjib Hammoudi, Olivier Hanon, Anarole Harrois, Coraline Hautem, Guillaume Hekimian, Nicholas Heming, Olivier Hermine, Sylvie Ho, Marie Houllier, Benjamin Huot, Tessa Huscenot, Wafa Ibn Saied, Ghilas Ikherbane, Meriem Imarazene, Patrick Ingiliz, Lina Iratni, Stephane Jaureguiberry, Jean-Francois Jean-Marc, Deleena Jeyarajasingham, Pauline Jouany, Veronique Jouis, Clement Jourdaine, Ouifiya Kafif, Rim Kallala, Sandrine Katsahian, Lilit Kelesyan, Vixra Keo, Flora Ketz, Warda Khamis, Enfel Khelili, Mehdi Khellaf, Christy Gaëlla Kotokpo Youkou, Ilias Kounis, Gaelle Kpalma, Jessica Krause, Vincent Labbe, Karine Lacombe, Jean-Marc Lacorte, Anne Gaelle Lafont, Emmanuel Lafont, Lynda Lagha, Lionel Lamhaut, Aymeric Lancelot, Cecilia Landman, Fanny Lanternier, Cecile Larcheveque, Caroline Lascoux Combe, Ludovic Lassel, Benjamin Laverdant, Christophe Lavergne, Jean-Rémi Lavillegrand, Pompilia Lazureanu, Loïc Le Guennec, Lamia Leberre, Claire Leblanc, Marion Leboyer, Francois Lecomte, Marine Lecorre, Romain Leenhardt, Marylou Lefebvre, Bénédicte Lefebvre, Paul Legendre, Anne Leger, Laurence Legros, Justyna Legrosse, Sébastien Lehuunghia, Julien Lemarec, Jeremie Leporrier-Ext, Manon Lesein, Hubert Lesur, Vincent Levy, Albert Levy, Edwige Lopes, Amanda Lopes, Vanessa Lopez, Julien Lopinto, Olivier Lortholary, Badr Louadah, Bénédicte Loze, Marie-Laure Lucas, Axelle Lucasamichi, Liem Binh Luong, Arouna Magazimama-Ext, David Maingret, Lakhdar Mameri, Philippe Manivet, Cylia Mansouri, Estelle Marcault, Jonathan Marey, Nathalie Marin, Clémence Marois, Olivier Martin, Lou Martineau, Cannelle Martinez-Lopez, Pierre Martyniuck, Pauline Mary De Farcy, Nessrine Marzouk, Rafik Masmoudi, Alexandre Mebazaa, Frédéric Mechai, Fabio Mecozzi, Chamseddine Mediouni, Bruno Megarbane, Mohamed Meghadecha, Élodie Mejean, Arsene Mekinian, Nour Mekki Abdelhadi, Rania Mekni, Thinhinan Sabrina Meliti, Breno Melo Lima, Paris Meng, Soraya Merbah, Fadhila Messani, Yasmine Messaoudi, Baboo-Irwinsingh Mewasing, Lydia Meziane, Carole Michelot-Burger, Françoise Mignot, Fadi Hillary Minka, Makoto Miyara, Pierre Moine, Jean-Michel Molina, Anaïs Montegnies-Boulet, Alexandra Monti, Claire Montlahuc, Anne-Lise Montout, Alexandre Moores, Caroline Morbieu, Helene Mortelette, Stéphane Mouly, Rosita Muzaffar, Cherifa Iness Nacerddine, Marine Nadal, Hajer Nadif, Kladoum Nassarmadji, Pierre Natella, Sandrine Ndingamondze, Stefan Neraal, Caroline Nguyen, Bao N'Guyen, Isabelle Nion Larmurier, Luc Nlomenyengue, Nicolas Noel, Hilario Nunes, Edris Omar, Zineb Ouazene, Elise Ouedraogo, Wassila Ouelaa, Anissa Oukhedouma, Yasmina Ould Amara, Herve Oya, Johanna Oziel, Thomas Padilla, Elena Paillaud, Solenne Paiva, Beatrice Parfait, Perrine Parize, Christophe Parizot, Antoine Parrot, Arthur Pavot, Laetitia Peaudecerf, Frédéric Pene, Marion Pepin, Julie Pernet, Claire Pernin, Mylène Petit, Olivier Peyrony, Marie-Pierre Pietri, Olivia Pietri, Marc Pineton De Chambrun, Michelle Pinson, Claire Pintado, Valentine Piquard, Christine Pires, Benjamin Planquette, Sandrine Poirier, Anne-Laure Pomel, Stéphanie Pons, Diane Ponscarme, Annegaelle Pourcelot, Valérie Pourcher, Anne Pouvaret, Florian Prever, Miresta Previlon, Margot Prevost, Marie-Julie Provoost, Cyril Quemeneur, Cédric Rafat, Agathe Rami, Brigitte Ranque, Maurice Raphael, Jean Herle Raphalen, Anna Rastoin, Mathieu Raux, Amani Rebai, Michael Reby, Alexis Regent, Asma Regrag, Matthieu Resche-Rigon, Quentin Ressaire, Christian Richard, Mariecaroline Richard, Maxence Robert, Benjamin Rohaut, Camille Rolland-Debord, Jacques Ropers, Anne-Marie Roque-Afonso, Charlotte Rosso, Mélanie Rousseaux, Nabila Rousseaux, Swasti Roux, Lorène Roux, Claire Rouzaud, Antoine Rozes, Emma Rubenstein, Jean-Marc Sabate, Sheila Sabet, Sophie-Caroline Sacleux, Nathalie Saidenberg Kermanach, Faouzi Saliba, Dominique Salmon, Laurent Savale, Guillaume Savary, Rebecca Sberro, Anne Scemla, Frederic Schlemmer, Mathieu Schwartz, Saïd Sedfi, Samia Sefir-Kribel, Philippe Seksik, Pierre Sellier, Agathe Selves, Nicole Sembach, Luca Semerano, Marie-Victoire Senat, Damien Sene, Alexandra Serris, Lucile Sese, Naima Sghiouar, Johanna Sigaux, Martin Siguier, Johanne Silvain, Noémie Simon, Tabassome Simon, Lina Innes Skandri, Miassa Slimani, Aurélie Snauwaert, Harry Sokol, Heithem Soliman, Nisrine Soltani, Benjamin Soyer, Gabriel Steg, Lydia Suarez, Tali-Anne Szwebel, Kossi Taffame, Yacine Tandjaoui-Lambiotte, Claire Tantet, Mariagrazia Tateo, Igor Theodose, Pierre clement Thiebaud, Caroline Thomas, Kelly Tiercelet, Julie Tisserand, Carole Tomczak, Krystel Torelino, Fatima Touam-Ext, Lilia Toumi, Gustave Toury, Mireille Toy-Miou, Olivia Tran Dinh Thanh Lien, Alexy Trandinh, Jean-Marc Treluyer, Baptiste Trinque, Jennifer Truchot, Sarah Tubiana, Simone Tunesi, Matthieu Turpin, Agathe Turpin, Tomas Urbina, Rafael Usubillaga Narvaez, Yurdagul Uzunhan, Prabakar Vaittinadaayar, Arnaud Valent, Maelle Valentian, Nadia Valin, Hélène Vallet, Marina Vaz, Miguel-Alejandro Vazquezibarra, Benoit Vedie, Laetitia Velly, Celine Verstuyft, Cedric Viallette, Eric Vicaut, Dorothee Vignes, Damien Vimpere, Myriam Virlouvet, Guillaume Voiriot, Lena Voisot, Emmanuel Weiss, Nicolas Weiss, Anaïs Winchenne, Youri Yordanov, Lara Zafrani, Mohamad Zaidan, Wissem Zaidi, Cathia Zak, Aida Zarhrate-Ghoul, Ouassila Zatout, Suzanne Zeino, Michel Zeitouni, Naïma Zemirli, Lorene Zerah, Ounsa Zia, Marianne Ziol, Oceane Zolario, Julien Zuber, Claire Andrejak, François Angoulvant, Delphine Bachelet, Marie Bartoli, Romain Basmaci, Sylvie Behillil, Marine Beluze, Dehbia Benkerrou, Krishna Bhavsar, Lila Bouadma, Sabelline Bouchez, Maude Bouscambert, Minerva Cervantes-Gonzalez, Anissa Chair, Catherine Chirouze, Alexandra Coelho, Sandrine Couffin-Cadiergues, Eric d’Ortenzio, Marie-Pierre Debray, Laurene Deconinck, Dominique Deplanque, Diane Descamps, Mathilde Desvallée, Alpha Diallo, Alphonsine Diouf, Céline Dorival, François Dubos, Brigitte Elharrar, Vincent Enouf, Hélène Esperou, Marina Esposito-Farese, Manuel Etienne, Eglantine Ferrand Devouge, Nathalie Gault, Alexandre Gaymard, Tristan Gigante, Morgane Gilg, Jérémie Guedj, Alexandre Hoctin, Isabelle Hoffmann, Ikram Houas, Jean-Sébastien Hulot, Salma Jaafoura, Florentia Kaguelidou, Sabrina Kali, Antoine Khalil, Coralie Khan, Cédric Laouénan, Samira Laribi, Minh Le, Quentin Le Hingrat, Soizic Le Mestre, Hervé Le Nagard, François-Xavier Lescure, Sophie Letrou, Yves Levy, Bruno Lina, Guillaume Lingas, Jean-Christophe Lucet, Denis Malvy, Marina Mambert, Amina Meziane, Hugo Mouquet, Jimmy Mullaert, Nadège Neant, Duc Nguyen, Marion Noret, Saad Nseir, Aurélie Papadopoulos, Christelle Paul, Nathan Peiffer-Smadja, Thomas Perpoint, Ventzislava Petrov-Sanchez, Gilles Peytavin, Huong Pham, Olivier Picone, Oriane Puéchal, Christian Rabaud, Manuel Rosa-Calatrava, Bénédicte Rossignol, Patrick Rossignol, Carine Roy, Marion Schneider, Richa Su, Coralie Tardivon, Marie-Capucine Tellier, François Téoulé, Olivier Terrier, Jean-François Timsit, Christelle Tual, Sylvie Van Der Werf, Noémie Vanel, Aurélie Veislinger, Benoit Visseaux, Aurélie Wiedemann, Yazdan Yazdanpanah, Loubna Alavoine, Charlotte Charpentier, Aline Dechanet, Jean-Luc Ecobichon, Wahiba Frezouls, Nadhira Houhou, Jonathan Lehacaut, Pauline Manchon, Mariama Nouroudine, Caroline Quintin, Michael Thy, Sylvie van der Werf, Valérie Vignali, Abir Chahine, Nawal Waucquier, Maria-Claire Migaud, Félix Djossou, Mayka Mergeay-Fabre, Aude Lucarelli, Magalie Demar, Léa Bruneau, Patrick Gérardin, Adrien Maillot, Christine Payet, Bruno Laviolle, Fabrice Laine, Christophe Paris, Mireille Desille-Dugast, Julie Fouchard, Thierry Pistone, Pauline Perreau, Valérie Gissot, Carole L.E. Goas, Samatha Montagne, Lucie Richard, Kévin Bouiller, Maxime Desmarets, Alexandre Meunier, Marilou Bourgeon, Benjamin Lefévre, Hélène Jeulin, Karine Legrand, Sandra Lomazzi, Bernard Tardy, Amandine Gagneux-Brunon, Frédérique Bertholon, Elisabeth Botelho-Nevers, Christelle Kouakam, Leturque Nicolas, Layidé Roufai, Karine Amat, Hélène Espérou, Samia Hendou, Giuseppe Foti, Giuseppe Citerio, Ernesto Contro, Alberto Pesci, Maria Grazia Valsecchi, Marina Cazzaniga, Giacomo Bellani, Jorge Abad, Giulia Accordino, Micol Angelini, Sergio Aguilera-Albesa, Aina Aguiló-Cucurull, Esra Akyüz Özkan, Ilad Alavi Darazam, Jonathan Antonio Roblero Albisures, Juan C. Aldave, Miquel Alfonso Ramos, Taj Ali Khan, Anna Aliberti, Seyed Alireza Nadji, Gulsum Alkan, Suzan A. AlKhater, Jerome Allardet-Servent, Luis M. Allende, Rebeca Alonso-Arias, Mohammed S. Alshahrani, Laia Alsina, Zahir Amoura, Arnau Antolí, Romain Arrestier, Mélodie Aubart, Teresa Auguet, Iryna Avramenko, Gökhan Aytekin, Axelle Azot, Seiamak Bahram, Fanny Bajolle, Fausto Baldanti, Aurélie Baldolli, Maite Ballester, Benoit Barrou, Federica Barzaghi, Sabrina Basso, Gulsum Iclal Bayhan, Liliana Bezrodnik, Agurtzane Bilbao, Geraldine Blanchard-Rohner, Ignacio Blanco, Adeline Blandinières, Daniel Blázquez-Gamero, Marketa Bloomfield, Mireia Bolivar-Prados, Raphael Borie, Elisabeth Botdhlo-Nevers, Aurore Bousquet, David Boutolleau, Claire Bouvattier, Oksana Boyarchuk, Juliette Bravais, M. Luisa Briones, Marie-Eve Brunner, Raffaele Bruno, Maria Rita P. Bueno, Huda Bukhari, Jacinta Bustamante, Juan José Cáceres Agra, Ruggero Capra, Raphael Carapito, Maria Carrabba, Carlos Casasnovas, Marion Caseris, Irene Cassaniti, Martin Castelle, Francesco Castelli, Martín Castillo de Vera, Mateus V. Castro, Emilie Catherinot, Jale Bengi Celik, Alessandro Ceschi, Martin Chalumeau, Bruno Charbit, Cécile Boulanger, Père Clavé, Bonaventura Clotet, Anna Codina, Cloé Comarmond, Patrizia Comoli, Angelo G. Corsico, Taner Coşkuner, Aleksandar Cvetkovski, Cyril Cyrus, David Dalmau, François Danion, David Ross Darley, Vincent Das, Nicolas Dauby, Stéphane Dauger, Paul De Munte, Loic de Pontual, Amin Dehban, Geoffroy Delplancq, Isabelle Desguerre, Antonio Di Sabatino, Jean-Luc Diehl, Stephanie Dobbelaere, Elena Domínguez-Garrido, Clément Dubost, Olov Ekwall, Şefika Elmas Bozdemir, Marwa H. Elnagdy, Melike Emiroglu, Akifumi Endo, Emine Hafize Erdeniz, Selma Erol Aytekin, Maria Pilar Etxart Lasa, Romain Euvrard, Giovanna Fabio, Laurence Faivre, Antonin Falck, Muriel Fartoukh, Morgane Faure, Miguel Fernandez Arquero, Ricard Ferrer, Jose Ferreres, Bruno Francois, Victoria Fumadó, Kitty S.C. Fung, Francesca Fusco, Alenka Gagro, Blanca Garcia Solis, Pierre Garçon, Pascale Gaussem, Zeynep Gayretli, Juana Gil-Herrera, Laurent Gilardin, Audrey Giraud Gatineau, Mònica Girona-Alarcón, Karen Alejandra Cifuentes Godínez, Jean-Christophe Goffard, Nacho Gonzales, Luis I. Gonzalez-Granado, Rafaela González-Montelongo, Antoine Guerder, Belgin Gülhan, Victor Daniel Gumucio, Leif Gunnar Hanitsch, Jan Gunst, Marta Gut, Jérôme Hadjadj, Selda Hancerli, Tetyana Hariyan, Nevin Hatipoglu, Deniz Heppekcan, Elisa Hernandez-Brito, Po-ki Ho, María Soledad Holanda-Peña, Juan P. Horcajada, Sami Hraiech, Linda Humbert, Ivan F.N. Hung, Alejandro D. Iglesias, Antonio Íñigo-Campos, Matthieu Jamme, María Jesús Arranz, Marie-Thérèse Jimeno, Iolanda Jordan, Saliha Kanık-Yüksek, Yalcin Kara, Aydın Karahan, Adem Karbuz, Kadriye Kart Yasar, Ozgur Kasapcopur, Kenichi Kashimada, Sevgi Keles, Yasemin Kendir Demirkol, Yasutoshi Kido, Can Kizil, Ahmet Osman Kılıç, Adam Klocperk, Antonia Koutsoukou, Zbigniew J. Król, Hatem Ksouri, Paul Kuentz, Arthur M.C. Kwan, Yat Wah M. Kwan, Janette S.Y. Kwok, Jean-Christophe Lagier, David S.Y. Lam, Vicky Lampropoulou, Fleur Le Bourgeois, Yee-Sin Leo, Rafael Leon Lopez, Daniel Leung, Michael Levin, Michael Levy, Romain Lévy, Zhi Li, Daniele Lilleri, Edson Jose Adrian Bolanos Lima, Agnes Linglart, Eduardo López-Collazo, José M. Lorenzo-Salazar, Céline Louapre, Catherine Lubetzki, Kwok-Cheung Lung, Charles-Edouard Luyt, David C. Lye, Cinthia Magnone, Enrico Marchioni, Carola Marioli, Majid Marjani, Laura Marques, Jesus Marquez Pereira, Andrea Martín-Nalda, David Martínez Pueyo, Javier Martinez-Picado, Iciar Marzana, Carmen Mata-Martínez, Alexis Mathian, Larissa R.B. Matos, Gail V. Matthews, Julien Mayaux, Raquel McLaughlin-Garcia, Philippe Meersseman, Jean-Louis Mège, Armand Mekontso-Dessap, Isabelle Melki, Federica Meloni, Jean-François Meritet, Paolo Merlani, Özge Metin Akcan, Mehdi Mezidi, Isabelle Migeotte, Maude Millereux, Matthieu Million, Tristan Mirault, Clotilde Mircher, Mehdi Mirsaeidi, Yoko Mizoguchi, Bhavi P. Modi, Francesco Mojoli, Elsa Moncomble, Abián Montesdeoca Melián, Antonio Morales Martinez, Francisco Morandeira, Pierre-Emmanuel Morange, Clémence Mordacq, Guillaume Morelle, Stéphane J. Mouly, Adrián Muñoz-Barrera, Cyril Nafati, Shintaro Nagashima, Yu Nakagama, Bénédicte Neven, João Farela Neves, Yuk-Yung Ng, Hubert Nielly, Yeray Novoa Medina, Esmeralda Nuñez Cuadros, Semsi Nur Karabela, J. Gonzalo Ocejo-Vinyals, Mehdi Oualha, Amani Ouedrani, Tayfun Özçelik, Aslinur Ozkaya-Parlakay, Michele Pagani, Maria Papadaki, Philippe Parola, Tiffany Pascreau, Stéphane Paul, Estela Paz-Artal, Sigifredo Pedraza, Nancy Carolina González Pellecer, Silvia Pellegrini, Rebeca Pérez de Diego, Xosé Luis Pérez-Fernández, Aurélien Philippe, Quentin Philippot, Adrien Picod, Marc Pineton de Chambrun, Antonio Piralla, Laura Planas-Serra, Dominique Ploin, Julien Poissy, Géraldine Poncelet, Garyphallia Poulakou, Marie S. Pouletty, Persia Pourshahnazari, Jia Li Qiu-Chen, Paul Quentric, Thomas Rambaud, Didier Raoult, Violette Raoult, Anne-Sophie Rebillat, Claire Redin, Léa Resmini, Pilar Ricart, Jean-Christophe Richard, Raúl Rigo-Bonnin, Nadia Rivet, Jacques G. Rivière, Gemma Rocamora-Blanch, Mathieu P. Rodero, Carlos Rodrigo, Luis Antonio Rodriguez, Carlos Rodriguez-Gallego, Agustí Rodriguez-Palmero, Carolina Soledad Romero, Anya Rothenbuhler, Damien Roux, Nikoletta Rovina, Flore Rozenberg, Yvon Ruch, Montse Ruiz, Maria Yolanda Ruiz del Prado, Juan Carlos Ruiz-Rodriguez, Joan Sabater-Riera, Kai Saks, Maria Salagianni, Oliver Sanchez, Adrián Sánchez-Montalvá, Silvia Sánchez-Ramón, Laire Schidlowski, Agatha Schluter, Julien Schmidt, Matthieu Schmidt, Catharina Schuetz, Cyril E. Schweitzer, Francesco Scolari, Luis Seijo, Analia Gisela Seminario, Piseth Seng, Sevtap Senoglu, Mikko Seppänen, Alex Serra Llovich, Virginie Siguret, Eleni Siouti, David M. Smadja, Nikaia Smith, Ali Sobh, Xavier Solanich, Jordi Solé-Violán, Catherine Soler, Betül Sözeri, Giulia Maria Stella, Yuriy Stepanovskiy, Annabelle Stoclin, Fabio Taccone, Jean-Luc Taupin, Simon J. Tavernier, Loreto Vidaur Tello, Benjamin Terrier, Guillaume Thiery, Karolina Thorn, Caroline Thumerelle, Imran Tipu, Martin Tolstrup, Gabriele Tomasoni, Julie Toubiana, Josep Trenado Alvarez, Vasiliki Triantafyllia, Jesús Troya, Owen T.Y. Tsang, Liina Tserel, Eugene Y.K. Tso, Alessandra Tucci, Şadiye Kübra Tüter Öz, Matilde Valeria Ursini, Takanori Utsumi, Pierre Vabres, Juan Valencia-Ramos, Ana Maria Van Den Rym, Isabelle Vandernoot, Valentina Velez-Santamaria, Silvia Patricia Zuniga Veliz, Mateus C. Vidigal, Sébastien Viel, Cédric Villain, Marie E. Vilaire-Meunier, Judit Villar-García, Audrey Vincent, Dimitri Van der Linden, Alla Volokha, Fanny Vuotto, Els Wauters, Alan K.L. Wu, Tak-Chiu Wu, Aysun Yahşi, Osman Yesilbas, Mehmet Yildiz, Barnaby E. Young, Ufuk Yükselmiş, Marco Zecca, Valentina Zuccaro, Jens Van Praet, Bart N. Lambrecht, Eva Van Braeckel, Cédric Bosteels, Levi Hoste, Eric Hoste, Fré Bauters, Jozefien De Clercq, Catherine Heijmans, Hans Slabbynck, Leslie Naesens, Benoit Florkin, Mary-Anne Young, Amanda Willis, Paloma Lapuente-Suanzes, Ana de Andrés-Martín, Matilda Berkell, Valerio Carelli, Alessia Fiorentino, Surbhi Malhotra, Alessandro Mattiaccio, Tommaso Pippucci, Marco Seri, Evelina Tacconelli, Michiel van Agtmael, Anne Geke Algera, Brent Appelman, Frank van Baarle, Diane Bax, Martijn Beudel, Harm Jan Bogaard, Marije Bomers, Peter Bonta, Lieuwe Bos, Michela Botta, Justin de Brabander, Godelieve de Bree, Sanne de Bruin, David T.P. Buis, Marianna Bugiani, Esther Bulle, Osoul Chouchane, Alex Cloherty, Mirjam Dijkstra, Dave A. Dongelmans, Romein W.G. Dujardin, Paul Elbers, Lucas Fleuren, Suzanne Geerlings, Theo Geijtenbeek, Armand Girbes, Bram Goorhuis, Martin P. Grobusch, Florianne Hafkamp, Laura Hagens, Jorg Hamann, Vanessa Harris, Robert Hemke, Sabine M. Hermans, Leo Heunks, Markus Hollmann, Janneke Horn, Joppe W. Hovius, Menno D. de Jong, Rutger Koning, Endry H.T. Lim, Niels van Mourik, Jeaninne Nellen, Esther J. Nossent, Frederique Paulus, Edgar Peters, Dan A.I. Pina-Fuentes, Tom van der Poll, Bennedikt Preckel, Jan M. Prins, Jorinde Raasveld, Tom Reijnders, Maurits C.F. J. de Rotte, Michiel Schinkel, Marcus J. Schultz, Femke A.P. Schrauwen, Alex Schuurmans, Jaap Schuurmans, Kim Sigaloff, Marleen A. Slim, Patrick Smeele, Marry Smit, Cornelis S. Stijnis, Willemke Stilma, Charlotte Teunissen, Patrick Thoral, Anissa M. Tsonas, Pieter R. Tuinman, Marc van der Valk, Denise P. Veelo, Carolien Volleman, Heder de Vries, Lonneke A. Vught, Michèle van Vugt, Dorien Wouters, A.H. Zwinderman, Matthijs C. Brouwer, W. Joost Wiersinga, Alexander P.J. Vlaar, Miranda F. Tompkins, Camille Alba, Daniel N. Hupalo, John Rosenberger, Gauthaman Sukumar, Matthew D. Wilkerson, Xijun Zhang, Justin Lack, Andrew J. Oler, Kerry Dobbs, Ottavia M. Delmonte, Jeffrey J. Danielson, Andrea Biondi, Laura Rachele Bettini, Mariella D’Angiò, Ilaria Beretta, Luisa Imberti, Alessandra Sottini, Virginia Quaresima, Eugenia Quiros-Roldan, Camillo Rossi, Riccardo Castagnoli, Daniela Montagna, Amelia Licari, and Gian Luigi Marseglia
Subjects: HLA, association, asymptomatic infection, COVID-19, population stratification, Genetics, QH426-470
Abstract: Summary: Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.
Published: 2024
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3. Directional versus ring-mode deep brain stimulation for Parkinson’s disease: protocol of a multi-centre double-blind randomised crossover trial

Author: Timo R. ten Brinke, Hannah Jergas, Vibuthi Sisodia, Michael T. Barbe, Vincent J. J. Odekerken, Dagmar Verbaan, Joke M. Dijk, Maarten Bot, Martijn Beudel, Pepijn van den Munckhof, P. Rick Schuurman, and Rob M. A. de Bie
Subjects: Parkinson’s disease, Deep brain stimulation, Directional deep brain stimulation, Steering subthalamic nucleus, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Background The effectiveness of Deep Brain Stimulation (DBS) therapy for Parkinson’s disease can be limited by side-effects caused by electrical current spillover into structures adjacent to the target area. The objective of the STEEred versus RING-mode DBS for Parkinson’s disease (STEERING) study is to investigate if directional DBS for Parkinson’s disease results in a better clinical outcome when compared to ring-mode DBS. Methods The STEERING study is a prospective multi-centre double-blind randomised crossover trial. Inclusion criteria are Parkinson’s disease, subthalamic nucleus DBS in a ‘classic’ ring-mode setting for a minimum of six months, and optimal ring-mode settings have been established. Participants are categorised into one of two subgroups according to their clinical response to the ring-mode settings as ‘responders’ (i.e., patient with a satisfactory effect of ring-mode DBS) or ‘non-responder’ (i.e., patient with a non-satisfactory effect of ring-mode DBS). A total of 64 responders and 38 non-responders will be included (total 102 patients). After an optimisation period in which an optimal directional setting is found, participants are randomised to first receive ring-mode DBS for 56 days (range 28–66) followed by directional DBS for 56 days (28–66) or vice-versa. The primary outcome is the difference between ring-mode DBS and directional DBS settings on the Movement Disorders Society Unified Parkinson’s Disease Rating Scale – Motor Evaluation (MDS-UPDRS-ME) in the off-medication state. Secondary outcome measures consist of MDS-UPDRS-ME in the on-medication state, MDS-UPDRS Activities of Daily Living, MDS-UPDRS Motor Complications–Dyskinesia, disease related quality of life measured with the Parkinson’s Disease Questionnaire 39, stimulation-induced side-effects, antiparkinsonian medication use, and DBS-parameters. Participants’ therapy preference is measured at the end of the study. Outcomes will be analysed for both responder and non-responder groups, as well as for both groups pooled together. Discussion The STEERING trial will provide insights into whether or not directional DBS should be standardly used in all Parkinson’s disease DBS patients or if directional DBS should only be used in a case-based approach. Trial registration This trial was registered on the Netherlands Trial Register, as trial NL6508 ( NTR6696 ) on June 23, 2017.
Published: 2023
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4. Does atrial fibrillation affect prognosis in hospitalised COVID-19 patients? A multicentre historical cohort study in the Netherlands

Author: Martijn Beudel, Martin E W Hemels, Auke C Reidinga, Tom Dormans, Joris R de Groot, Suat Simsek, Kees Brinkman, Daisy Rusch, Renee A Douma, Niels C Gritters van den Oever, Brent Appelman, Jocelyn R Spruit, René W M M Jansen, Tim A C de Vries, Lianne R de Haan, Hazra S Moeniralam, Martijn de Kruif, and Robert J Schuurman
Subjects: Medicine
Abstract: Objectives The aim of this multicentre COVID-PREDICT study (a nationwide observational cohort study that aims to better understand clinical course of COVID-19 and to predict which COVID-19 patients should receive which treatment and which type of care) was to determine the association between atrial fibrillation (AF) and mortality, intensive care unit (ICU) admission, complications and discharge destination in hospitalised COVID-19 patients.Setting Data from a historical cohort study in eight hospitals (both academic and non-academic) in the Netherlands between January 2020 and July 2021 were used in this study.Participants 3064 hospitalised COVID-19 patients >18 years old.Primary and secondary outcome measures The primary outcome was the incidence of new-onset AF during hospitalisation. Secondary outcomes were the association between new-onset AF (vs prevalent or non-AF) and mortality, ICU admissions, complications and discharge destination, performed by univariable and multivariable logistic regression analyses.Results Of the 3064 included patients (60.6% men, median age: 65 years, IQR 55–75 years), 72 (2.3%) patients had prevalent AF and 164 (5.4%) patients developed new-onset AF during hospitalisation. Compared with patients without AF, patients with new-onset AF had a higher incidence of death (adjusted OR (aOR) 1.71, 95% CI 1.17 to 2.59) an ICU admission (aOR 5.45, 95% CI 3.90 to 7.61). Mortality was non-significantly different between patients with prevalent AF and those with new-onset AF (aOR 0.97, 95% CI 0.53 to 1.76). However, new-onset AF was associated with a higher incidence of ICU admission and complications compared with prevalent AF (OR 6.34, 95% CI 2.95 to 13.63, OR 3.04, 95% CI 1.67 to 5.55, respectively).Conclusion New-onset AF was associated with an increased incidence of death, ICU admission, complications and a lower chance to be discharged home. These effects were far less pronounced in patients with prevalent AF. Therefore, new-onset AF seems to represent a marker of disease severity, rather than a cause of adverse outcomes.
Published: 2023
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5. What is the aetiology of dysnatraemia in COVID-19 and how is this related to outcomes in patients admitted during earlier and later COVID-19 waves? A multicentre, retrospective observational study in 11 Dutch hospitals

Author: Babette Verkouteren, Dan Piña-Fuentes, Martijn Beudel, Thomas Ludden, Rik H G Olde Engberink, Tom Dormans, Martijn D de Kruif, Suat Simsek, Joop P van den Bergh, Hazra Moeniralam, Renee Douma, Kees Brinkman, Wouter Hinsenveld, Lucas Ramos, Anne Pirson, Deborah Hubers, Shi Hu, Rajat Thomas, Michiel Schinkel, Caroline E Wyers, Daisy Rusch, Lianne de Haan, Niels C Gritters van den Oever, Nienke Paternotte, Robert-Jan Goldhoorn, Brent Appelman, Esther Lems, Marije ten Wolde, Esther K Haspels-Hogervorst, Neyma Bokhizzou, Niels Gritters van den Oever, Joop van den Bergh, Martijn de Kruif, Helen Leavis, Derk Arts, Nick Nurmohamed, Rens Reeskamp, Willem Herter, Bas Vonk, Ricardo Lopes, Deborah Huberts, Marije Wolfers, Sander de Kuij, Sophie Noordzij, Sibbeliene van den Bosch, Benthe Verhoef, Michele Methorst, Shahan Darwesh, Tijn van Egmond, Gulsum Nasim, Hamza Ali, Lars de Boer, Myrthe Nagel, Maud Koenis, Agnetha Bijlsma, Britt Balvers, Isabella Ghauharali, Jelle de Jongh, Maira Emanuel, Nisrine Aynaou, Rosemarie de Ridder, Insaff Darraz, Oumaima Darraz, Alanar Cinar, Jesse Roosen, Larissa Heideman, Asabi Leliveld, Dana Ruijter, Neeltje Rosenberg, Djoeke Woutman, Tom Vermeulen, Sam de Joode, Willem Berger, Ozgu Varan, Soesja Pinto, Sientje Sluis, Bibi Kuiper, Tim van der Putten, Dominique Bosje, Mahunda Sinyangwe, Roos van Rhijn, Koen Kruif, Miriam den Heijer, Koen de Kruijf, Sam Hofhuis, Gwendolyn Telting, Susan van der Lei, Pien van Paassen, Emil ter Veer, Krijna Opschoor, Camille Breukhoven, Florine Jiwa, Peter de Gooyer, Jan Vrijdag, Stans van Gelder, Anne Pannekoek, Laura Dommershuijzen, Estelle Adang, Maud van Maren, Isabel Koop, Bart Sanders, Joukje Wanten, Dax Trommelen, Fleur Smeets, Kyra Heuvelings, Maud Cox, Milou Rademaekers, Vivian Hendrikx, Ilona van Rooij, Wendy Heuts, Laura Oudeman, Evelien Brans, Karin Slot, Kirsten Boerma-Argelo, Wilma Kok, Lieke Harmsen, Ingrid Boerema, Anne Raafs, Anne Smaal, Bibiane Pop, Carmen Waterink, Casper Vrij, Daphne van der Willik, Frederic Reitsma, Imogene Pieters, Jade Logger, Laura Sijben, Maikel Peeters, Mariël Teunissen, Marije Blok-Hoos, Marjolein Ketels, Michiel Henkens, Mireille Spanjers, Monique Jacob-Dols, Patrick de Hoogt, Rik Houben, Roos van Gorp, and Josien Jansen
Subjects: Medicine
Abstract: Objectives To evaluate the relationship among dysnatraemia at hospital presentation and duration of admission, risk of intensive care unit (ICU) admission and all-cause mortality and to assess the underlying pathophysiological mechanism of hyponatraemia in patients with COVID-19. Our hypothesis is that both hyponatraemia and hypernatraemia at presentation are associated with adverse outcomes.Design Observational study.Setting Secondary care; 11 Dutch hospitals (2 university and 9 general hospitals).Participants An analysis was performed within the retrospective multicentre cohort study COVIDPredict. 7811 patients were included (60% men, 40% women) between 24 February 2020 and 9 August 2022. Patients who were ≥18 years with PCR-confirmed COVID-19 or CT with COVID-19 reporting and data system score≥4 and alternative diagnosis were included. Patients were excluded when serum sodium levels at presentation were not registered in the database or when they had been transferred from another participating hospital.Outcome measures We studied demographics, medical history, symptoms and outcomes. Patients were stratified according to serum sodium concentration and urinary sodium excretion.Results Hyponatraemia was present in 2677 (34.2%) patients and hypernatraemia in 126 (1.6%) patients. Patients with hyponatraemia presented more frequently with diarrhoea, lower blood pressure and tachycardia. Hyponatraemia was, despite a higher risk for ICU admission (OR 1.27 (1.11–1.46; p
Published: 2023
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6. Comparison of [18F]-FDOPA PET and [123I]-FP-CIT SPECT acquired in clinical practice for assessing nigrostriatal degeneration in patients with a clinically uncertain parkinsonian syndrome

Author: Elon Wallert, Erwann Letort, Friso van der Zant, Ania Winogrodzka, Henk Berendse, Martijn Beudel, Rob de Bie, Jan Booij, Pieter Raijmakers, and Elsmarieke van de Giessen
Subjects: 18F-FDOPA, PET, Dopamine transporter, 123I-FP-CIT SPECT, Nigrostriatal degeneration, Parkinsonism, Medical physics. Medical radiology. Nuclear medicine, R895-920
Abstract: Abstract Purpose Two commonly used imaging techniques to aid in the diagnosis of neurodegenerative parkinsonian syndromes are dopamine transporter (DAT) imaging with [123I]-FP-CIT single-photon emission computed tomography (DAT-SPECT) and positron emission tomography with [18F]-FDOPA (FDOPA-PET). This paper provides a unique series of parkinsonian patients who received both FDOPA-PET and DAT-SPECT in routine clinical practice and compares the reported results to assess potential differences between these two imaging techniques. Methods We present 11 patients with a clinically uncertain parkinsonian syndrome (CUPS), who received both FDOPA-PET and DAT-SPECT. All patients received an FDOPA-PET scan and DAT-SPECT as part of routine clinical care. Results The median time between the F-DOPA-PET scan and DAT-SPECT scan was 6 months (range 0–15 months). There was a discrepancy in the reported results of the FDOPA-PET and DAT-SPECT scans in nine patients, including 7 patients whose FDOPA-PET scan was reportedly normal, whereas their DAT-SPECT scan was abnormal. Conclusions In this case series of CUPS patients, DAT-SPECT was more often rated as abnormal than FDOPA-PET. The striatal loss of FDOPA uptake can be less pronounced than that of DAT binding in CUPS patients in early disease stages. Consequently, the interpretation of FDOPA-PET scans in CUPS can sometimes be challenging in routine practice.
Published: 2022
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7. Editorial: The role of the basal ganglia in somatosensory-motor interactions: evidence from neurophysiology and behavior, volume II

Author: Martijn Beudel, Antonella Macerollo, Matt J. N. Brown, and Robert Chen
Subjects: basal ganglia (BG), deep brain stimulation (DBS), micro electrode recording, local field potential (LFP), sensorimotor, traumatic brain injury (TBI), Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Published: 2023
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8. Predictors for extubation failure in COVID-19 patients using a machine learning approach

Author: Lucas M. Fleuren, Tariq A. Dam, Michele Tonutti, Daan P. de Bruin, Robbert C. A. Lalisang, Diederik Gommers, Olaf L. Cremer, Rob J. Bosman, Sander Rigter, Evert-Jan Wils, Tim Frenzel, Dave A. Dongelmans, Remko de Jong, Marco Peters, Marlijn J. A. Kamps, Dharmanand Ramnarain, Ralph Nowitzky, Fleur G. C. A. Nooteboom, Wouter de Ruijter, Louise C. Urlings-Strop, Ellen G. M. Smit, D. Jannet Mehagnoul-Schipper, Tom Dormans, Cornelis P. C. de Jager, Stefaan H. A. Hendriks, Sefanja Achterberg, Evelien Oostdijk, Auke C. Reidinga, Barbara Festen-Spanjer, Gert B. Brunnekreef, Alexander D. Cornet, Walter van den Tempel, Age D. Boelens, Peter Koetsier, Judith Lens, Harald J. Faber, A. Karakus, Robert Entjes, Paul de Jong, Thijs C. D. Rettig, Sesmu Arbous, Sebastiaan J. J. Vonk, Mattia Fornasa, Tomas Machado, Taco Houwert, Hidde Hovenkamp, Roberto Noorduijn Londono, Davide Quintarelli, Martijn G. Scholtemeijer, Aletta A. de Beer, Giovanni Cinà, Adam Kantorik, Tom de Ruijter, Willem E. Herter, Martijn Beudel, Armand R. J. Girbes, Mark Hoogendoorn, Patrick J. Thoral, Paul W. G. Elbers, and the Dutch ICU Data Sharing Against Covid-19 Collaborators
Subjects: Extubation, Prediction, Risk factors, Extubation failure, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Introduction Determining the optimal timing for extubation can be challenging in the intensive care. In this study, we aim to identify predictors for extubation failure in critically ill patients with COVID-19. Methods We used highly granular data from 3464 adult critically ill COVID patients in the multicenter Dutch Data Warehouse, including demographics, clinical observations, medications, fluid balance, laboratory values, vital signs, and data from life support devices. All intubated patients with at least one extubation attempt were eligible for analysis. Transferred patients, patients admitted for less than 24 h, and patients still admitted at the time of data extraction were excluded. Potential predictors were selected by a team of intensive care physicians. The primary and secondary outcomes were extubation without reintubation or death within the next 7 days and within 48 h, respectively. We trained and validated multiple machine learning algorithms using fivefold nested cross-validation. Predictor importance was estimated using Shapley additive explanations, while cutoff values for the relative probability of failed extubation were estimated through partial dependence plots. Results A total of 883 patients were included in the model derivation. The reintubation rate was 13.4% within 48 h and 18.9% at day 7, with a mortality rate of 0.6% and 1.0% respectively. The grandient-boost model performed best (area under the curve of 0.70) and was used to calculate predictor importance. Ventilatory characteristics and settings were the most important predictors. More specifically, a controlled mode duration longer than 4 days, a last fraction of inspired oxygen higher than 35%, a mean tidal volume per kg ideal body weight above 8 ml/kg in the day before extubation, and a shorter duration in assisted mode (
Published: 2021
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9. The Dutch Data Warehouse, a multicenter and full-admission electronic health records database for critically ill COVID-19 patients

Author: Lucas M. Fleuren, Tariq A. Dam, Michele Tonutti, Daan P. de Bruin, Robbert C. A. Lalisang, Diederik Gommers, Olaf L. Cremer, Rob J. Bosman, Sander Rigter, Evert-Jan Wils, Tim Frenzel, Dave A. Dongelmans, Remko de Jong, Marco Peters, Marlijn J. A. Kamps, Dharmanand Ramnarain, Ralph Nowitzky, Fleur G. C. A. Nooteboom, Wouter de Ruijter, Louise C. Urlings-Strop, Ellen G. M. Smit, D. Jannet Mehagnoul-Schipper, Tom Dormans, Cornelis P. C. de Jager, Stefaan H. A. Hendriks, Sefanja Achterberg, Evelien Oostdijk, Auke C. Reidinga, Barbara Festen-Spanjer, Gert B. Brunnekreef, Alexander D. Cornet, Walter van den Tempel, Age D. Boelens, Peter Koetsier, Judith Lens, Harald J. Faber, A. Karakus, Robert Entjes, Paul de Jong, Thijs C. D. Rettig, Sesmu Arbous, Sebastiaan J. J. Vonk, Mattia Fornasa, Tomas Machado, Taco Houwert, Hidde Hovenkamp, Roberto Noorduijn-Londono, Davide Quintarelli, Martijn G. Scholtemeijer, Aletta A. de Beer, Giovanni Cina, Martijn Beudel, Willem E. Herter, Armand R. J. Girbes, Mark Hoogendoorn, Patrick J. Thoral, and Paul W. G. Elbers
Subjects: Database, Big data, COVID-19, Data sharing, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background The Coronavirus disease 2019 (COVID-19) pandemic has underlined the urgent need for reliable, multicenter, and full-admission intensive care data to advance our understanding of the course of the disease and investigate potential treatment strategies. In this study, we present the Dutch Data Warehouse (DDW), the first multicenter electronic health record (EHR) database with full-admission data from critically ill COVID-19 patients. Methods A nation-wide data sharing collaboration was launched at the beginning of the pandemic in March 2020. All hospitals in the Netherlands were asked to participate and share pseudonymized EHR data from adult critically ill COVID-19 patients. Data included patient demographics, clinical observations, administered medication, laboratory determinations, and data from vital sign monitors and life support devices. Data sharing agreements were signed with participating hospitals before any data transfers took place. Data were extracted from the local EHRs with prespecified queries and combined into a staging dataset through an extract–transform–load (ETL) pipeline. In the consecutive processing pipeline, data were mapped to a common concept vocabulary and enriched with derived concepts. Data validation was a continuous process throughout the project. All participating hospitals have access to the DDW. Within legal and ethical boundaries, data are available to clinicians and researchers. Results Out of the 81 intensive care units in the Netherlands, 66 participated in the collaboration, 47 have signed the data sharing agreement, and 35 have shared their data. Data from 25 hospitals have passed through the ETL and processing pipeline. Currently, 3464 patients are included in the DDW, both from wave 1 and wave 2 in the Netherlands. More than 200 million clinical data points are available. Overall ICU mortality was 24.4%. Respiratory and hemodynamic parameters were most frequently measured throughout a patient's stay. For each patient, all administered medication and their daily fluid balance were available. Missing data are reported for each descriptive. Conclusions In this study, we show that EHR data from critically ill COVID-19 patients may be lawfully collected and can be combined into a data warehouse. These initiatives are indispensable to advance medical data science in the field of intensive care medicine.
Published: 2021
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10. Intramuscular adipose tissue at level Th12 is associated with survival in COVID‐19

Author: Alain R. Viddeleer, Joost Raaphorst, Minoesch Min, Ludo F.M. Beenen, Maeke J. Scheerder, Alexander P.J. Vlaar, Amsterdam UMC COVID‐19 Biobank, Martijn Beudel, and Robert Hemke
Subjects: Diseases of the musculoskeletal system, RC925-935, Human anatomy, QM1-695
Published: 2021
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11. Risk factors for adverse outcomes during mechanical ventilation of 1152 COVID-19 patients: a multicenter machine learning study with highly granular data from the Dutch Data Warehouse

Author: Lucas M. Fleuren, Michele Tonutti, Daan P. de Bruin, Robbert C. A. Lalisang, Tariq A. Dam, Diederik Gommers, Olaf L. Cremer, Rob J. Bosman, Sebastiaan J. J. Vonk, Mattia Fornasa, Tomas Machado, Nardo J. M. van der Meer, Sander Rigter, Evert-Jan Wils, Tim Frenzel, Dave A. Dongelmans, Remko de Jong, Marco Peters, Marlijn J. A. Kamps, Dharmanand Ramnarain, Ralph Nowitzky, Fleur G. C. A. Nooteboom, Wouter de Ruijter, Louise C. Urlings-Strop, Ellen G. M. Smit, D. Jannet Mehagnoul-Schipper, Tom Dormans, Cornelis P. C. de Jager, Stefaan H. A. Hendriks, Evelien Oostdijk, Auke C. Reidinga, Barbara Festen-Spanjer, Gert Brunnekreef, Alexander D. Cornet, Walter van den Tempel, Age D. Boelens, Peter Koetsier, Judith Lens, Sefanja Achterberg, Harald J. Faber, A. Karakus, Menno Beukema, Robert Entjes, Paul de Jong, Taco Houwert, Hidde Hovenkamp, Roberto Noorduijn Londono, Davide Quintarelli, Martijn G. Scholtemeijer, Aletta A. de Beer, Giovanni Cinà, Martijn Beudel, Nicolet F. de Keizer, Mark Hoogendoorn, Armand R. J. Girbes, Willem E. Herter, Paul W. G. Elbers, Patrick J. Thoral, and Dutch ICU Data Sharing Against COVID-19 Collaborators
Subjects: COVID-19, Mortality prediction, Risk factors, Machine learning, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background The identification of risk factors for adverse outcomes and prolonged intensive care unit (ICU) stay in COVID-19 patients is essential for prognostication, determining treatment intensity, and resource allocation. Previous studies have determined risk factors on admission only, and included a limited number of predictors. Therefore, using data from the highly granular and multicenter Dutch Data Warehouse, we developed machine learning models to identify risk factors for ICU mortality, ventilator-free days and ICU-free days during the course of invasive mechanical ventilation (IMV) in COVID-19 patients. Methods The DDW is a growing electronic health record database of critically ill COVID-19 patients in the Netherlands. All adult ICU patients on IMV were eligible for inclusion. Transfers, patients admitted for less than 24 h, and patients still admitted at time of data extraction were excluded. Predictors were selected based on the literature, and included medication dosage and fluid balance. Multiple algorithms were trained and validated on up to three sets of observations per patient on day 1, 7, and 14 using fivefold nested cross-validation, keeping observations from an individual patient in the same split. Results A total of 1152 patients were included in the model. XGBoost models performed best for all outcomes and were used to calculate predictor importance. Using Shapley additive explanations (SHAP), age was the most important demographic risk factor for the outcomes upon start of IMV and throughout its course. The relative probability of death across age values is visualized in Partial Dependence Plots (PDPs), with an increase starting at 54 years. Besides age, acidaemia, low P/F-ratios and high driving pressures demonstrated a higher probability of death. The PDP for driving pressure showed a relative probability increase starting at 12 cmH2O. Conclusion Age is the most important demographic risk factor of ICU mortality, ICU-free days and ventilator-free days throughout the course of invasive mechanical ventilation in critically ill COVID-19 patients. pH, P/F ratio, and driving pressure should be monitored closely over the course of mechanical ventilation as risk factors predictive of these outcomes.
Published: 2021
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12. Diving into the subcortex: The potential of chronic subcortical sensing for unravelling basal ganglia function and optimization of deep brain stimulation

Author: Bart E.K.S. Swinnen, Arthur W. Buijink, Dan Piña-Fuentes, Rob M.A. de Bie, and Martijn Beudel
Subjects: Subcortex, Basal ganglia, Sensing, DBS, Adaptive, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Subcortical structures are a relative neurophysiological ‘terra incognita’ owing to their location within the skull. While perioperative subcortical sensing has been performed for more than 20 years, the neurophysiology of the basal ganglia in the home setting has remained almost unexplored. However, with the recent advent of implantable pulse generators (IPG) that are able to record neural activity, the opportunity to chronically record local field potentials (LFPs) directly from electrodes implanted for deep brain stimulation opens up. This allows for a breakthrough of chronic subcortical sensing into fundamental research and clinical practice. In this review an extensive overview of the current state of subcortical sensing is provided. The widespread potential of chronic subcortical sensing for investigational and clinical use is discussed. Finally, status and future perspectives of the most promising application of chronic subcortical sensing —i.e., adaptive deep brain stimulation (aDBS)— are discussed in the context of movement disorders. The development of aDBS based on both chronic subcortical and cortical sensing has the potential to dramatically change clinical practice and the life of patients with movement disorders. However, several barriers still stand in the way of clinical implementation. Advancements regarding IPG and lead technology, physiomarkers, and aDBS algorithms as well as harnessing artificial intelligence, multimodality and sensing in the naturalistic setting are needed to bring aDBS to clinical practice.
Published: 2022
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13. Acute effects of adaptive Deep Brain Stimulation in Parkinson’s disease

Author: Dan Piña-Fuentes, J. Marc C. van Dijk, Jonathan C. van Zijl, Harmen R. Moes, Teus van Laar, D.L.Marinus Oterdoom, Simon Little, Peter Brown, and Martijn Beudel
Subjects: Parkinson’s disease, Adaptive deep brain stimulation, Subthalamic nucleus, Local field potentials, Beta oscillations, Closed-loop, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Background: Beta-based adaptive Deep Brain Stimulation (aDBS) is effective in Parkinson’s disease (PD), when assessed in the immediate post-implantation phase. However, the potential benefits of aDBS in patients with electrodes chronically implanted, in whom changes due to the microlesion effect have disappeared, are yet to be assessed. Methods: To determine the acute effectiveness and side-effect profile of aDBS in PD compared to conventional continuous DBS (cDBS) and no stimulation (NoStim), years after DBS implantation, 13 PD patients undergoing battery replacement were pseudo-randomised in a crossover fashion, into three conditions (NoStim, aDBS or cDBS), with a 2-min interval between them. Patient videos were blindly evaluated using a short version of the Unified Parkinson’s Disease Rating Scale (subUPDRS), and the Speech Intelligibility Test (SIT). Results: Mean disease duration was 16 years, and the mean time since DBS-implantation was 6.9 years. subUPDRS scores (11 patients tested) were significantly lower both in aDBS (p=
Published: 2020
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14. Overweight and Obesity Are Associated With Acute Kidney Injury and Acute Respiratory Distress Syndrome, but Not With Increased Mortality in Hospitalized COVID-19 Patients: A Retrospective Cohort Study

Author: Jamie van Son, Sabrina M. Oussaada, Aydin Şekercan, Martijn Beudel, Dave A. Dongelmans, Sander van Assen, Ingo A. Eland, Hazra S. Moeniralam, Tom P. J. Dormans, Colin A. J. van Kalkeren, Renée A. Douma, Daisy Rusch, Suat Simsek, Limmie Liu, Ruud S. Kootte, Caroline E. Wyers, Richard G. IJzerman, Joop P. van den Bergh, Coen D. A. Stehouwer, Max Nieuwdorp, Kasper W. ter Horst, and Mireille J. Serlie
Subjects: COVID-19, obesity, overweight, complications, mortality, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: ObjectiveTo evaluate the association between overweight and obesity on the clinical course and outcomes in patients hospitalized with COVID-19.DesignRetrospective, observational cohort study.MethodsWe performed a multicenter, retrospective, observational cohort study of hospitalized COVID-19 patients to evaluate the associations between overweight and obesity on the clinical course and outcomes.ResultsOut of 1634 hospitalized COVID-19 patients, 473 (28.9%) had normal weight, 669 (40.9%) were overweight, and 492 (30.1%) were obese. Patients who were overweight or had obesity were younger, and there were more women in the obese group. Normal-weight patients more often had pre-existing conditions such as malignancy, or were organ recipients. During admission, patients who were overweight or had obesity had an increased probability of acute respiratory distress syndrome [OR 1.70 (1.26-2.30) and 1.40 (1.01-1.96)], respectively and acute kidney failure [OR 2.29 (1.28-3.76) and 1.92 (1.06-3.48)], respectively. Length of hospital stay was similar between groups. The overall in-hospital mortality rate was 27.7%, and multivariate logistic regression analyses showed that overweight and obesity were not associated with increased mortality compared to normal-weight patients.ConclusionIn this study, overweight and obesity were associated with acute respiratory distress syndrome and acute kidney injury, but not with in-hospital mortality nor length of hospital stay.
Published: 2021
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15. Some Patients Are More Equal Than Others: Variation in Ventilator Settings for Coronavirus Disease 2019 Acute Respiratory Distress Syndrome

Author: Tariq A. Dam, MD, Harm-Jan de Grooth, MD, PhD, Thomas Klausch, PhD, Lucas M. Fleuren, MD, Daan P. de Bruin, MSc, Robert Entjes, MD, Thijs C. D. Rettig, MD, PhD, Dave A. Dongelmans, MD, PhD, Age D. Boelens, MD, Sander Rigter, MD, Stefaan H. A. Hendriks, MD, Remko de Jong, MD, Marlijn J. A Kamps, MD, Marco Peters, MD, A. Karakus, MD, Diederik Gommers, MD, PhD, Dharmanand Ramnarain, MD, Evert-Jan Wils, MD, PhD, Sefanja Achterberg, MD, PhD, Ralph Nowitzky, MD, Walter van den Tempel, MD, Cornelis P. C. de Jager, MD, PhD, Fleur G. C. A. Nooteboom, MD, Evelien Oostdijk, MD, PhD, Peter Koetsier, MD, Alexander D. Cornet, MD, PhD, FRCP, Auke C. Reidinga, MD, Wouter de Ruijter, MD, PhD, Rob J. Bosman, MD, Tim Frenzel, MD, PhD, Louise C. Urlings-Strop, MD, PhD, Paul de Jong, MD, Ellen G. M. Smit, MD, Olaf L. Cremer, MD, PhD, D. Jannet Mehagnoul-Schipper, MD, PhD, Harald J. Faber, MD, Judith Lens, MD, Gert B. Brunnekreef, MD, Barbara Festen-Spanjer, MD, Tom Dormans, MD, PhD, Annemieke Dijkstra, MD, Bram Simons, MD, A. A. Rijkeboer, MD, Sesmu Arbous, MD, PhD, Marcel Aries, MD, PhD, Menno Beukema, MD, Daniël Pretorius, MD, Rutger van Raalte, MD, Martijn van Tellingen, MD, EDIC, Niels C. Gritters van den Oever, MD, Robbert C. A. Lalisang, MD, Michele Tonutti, MRes, Armand R. J. Girbes, MD, PhD, EDIC, Mark Hoogendoorn, PhD, Patrick J. Thoral, MD, EDIC, Paul W. G. Elbers, MD, PhD, EDIC, on behalf of the Dutch ICU Data Sharing Against COVID-19 Collaborators, Remko van den Akker, Tom A. Rijpstra, M. C. Reuland, Klaas Sierk Arnold, Arend Jan Meinders, Nicolas Schroten, Laura van Manen, Leon Montenij, Julia Koeter, J. W. Fijen, Jasper van Bommel, Roy van den Berg, Martha de Bruin, Roger van Rietschote, Ellen van Geest, Koen S. Simons, Anisa Hana, Joost Labout, Michael Kuiper, Albertus Beishuizen, Bart van de Gaauw, Roos Renckens, B. van den Bogaard, Peter Pickkers, Pim van der Heiden, Dennis Geutjes, Claudia (C. W.) van Gemeren, Emma Rademaker, Frits H. M. van Osch, Johan Lutisan, Jacomar J. M. van Koesveld, Bart P. Grady, Martijn de Kruif, Martin E. Haan, Luca Roggeveen, Dagmar M. Ouweneel, Ronald Driessen, Jan Peppink, G. J. Zijlstra, A. J. van Tienhoven, Evelien van der Heiden, Jan Jaap Spijkstra, Hans van der Spoel, Angelique de Man, Heder J. de Vries, Fuda van Diggelen, Ali el Hassouni, David Romero Guzman, Sandjai Bhulai, Sebastiaan J. J. Vonk, Mattia Fornasa, Tomas Machado, Adam Izdebski, Taco Houwert, Hidde Hovenkamp, Roberto Noorduijn Londono, Davide Quintarelli, Martijn G. Scholtemeijer, Aletta A. de Beer, Giovanni Cinà, Willem E. Herter, Michael de Neree tot Babberich, Olivier Thijssens, Lot Wagemakers, Hilde G. A. van der Pol, Tom Hendriks, Julie Berend, Virginia Ceni Silva, Robert F. J. Kullberg, Leo Heunks, Nicole Juffermans, Arjen J. C. Slooter, Martijn Beudel, and Nicolet F. de Keizer
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: OBJECTIVES:. As coronavirus disease 2019 is a novel disease, treatment strategies continue to be debated. This provides the intensive care community with a unique opportunity as the population of coronavirus disease 2019 patients requiring invasive mechanical ventilation is relatively homogeneous compared with other ICU populations. We hypothesize that the novelty of coronavirus disease 2019 and the uncertainty over its similarity with noncoronavirus disease 2019 acute respiratory distress syndrome resulted in substantial practice variation between hospitals during the first and second waves of coronavirus disease 2019 patients. DESIGN:. Multicenter retrospective cohort study. SETTING:. Twenty-five hospitals in the Netherlands from February 2020 to July 2020, and 14 hospitals from August 2020 to December 2020. PATIENTS:. One thousand two hundred ninety-four critically ill intubated adult ICU patients with coronavirus disease 2019 were selected from the Dutch Data Warehouse. Patients intubated for less than 24 hours, transferred patients, and patients still admitted at the time of data extraction were excluded. MEASUREMENTS AND MAIN RESULTS:. We aimed to estimate between-ICU practice variation in selected ventilation parameters (positive end-expiratory pressure, Fio2, set respiratory rate, tidal volume, minute volume, and percentage of time spent in a prone position) on days 1, 2, 3, and 7 of intubation, adjusted for patient characteristics as well as severity of illness based on Pao2/Fio2 ratio, pH, ventilatory ratio, and dynamic respiratory system compliance during controlled ventilation. Using multilevel linear mixed-effects modeling, we found significant (p ≤ 0.001) variation between ICUs in all ventilation parameters on days 1, 2, 3, and 7 of intubation for both waves. CONCLUSIONS:. This is the first study to clearly demonstrate significant practice variation between ICUs related to mechanical ventilation parameters that are under direct control by intensivists. Their effect on clinical outcomes for both coronavirus disease 2019 and other critically ill mechanically ventilated patients could have widespread implications for the practice of intensive care medicine and should be investigated further by causal inference models and clinical trials.
Published: 2021
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16. Predicting mortality of individual patients with COVID-19: a multicentre Dutch cohort

Author: Henk A Marquering, Dan Piña-Fuentes, Martijn Beudel, Iwan C C van der Horst, Auke C Reidinga, Roger J M W Rennenberg, Tom Dormans, Martijn D de Kruif, Marcus L F Janssen, Marcel J H Aries, Suat Simsek, Joop P van den Bergh, Lucas A Ramos, Paul W G Elbers, W Joost Wiersinga, Maarten C Ottenhoff, Wouter Potters, Deborah Hubers, Shi Hu, Egill A Fridgeirsson, Rajat Thomas, Christian Herff, Pieter Kubben, Max Welling, Lucas M Fleuren, Michiel Schinkel, Peter G Noordzij, Caroline E Wyers, David T B Buis, Ella H C van den Hout, Daisy Rusch, Kim C E Sigaloff, Renee A Douma, Lianne de Haan, Niels C Gritters van den Oever, and Guido A van Wingen
Subjects: Medicine
Abstract: Objective Develop and validate models that predict mortality of patients diagnosed with COVID-19 admitted to the hospital.Design Retrospective cohort study.Setting A multicentre cohort across 10 Dutch hospitals including patients from 27 February to 8 June 2020.Participants SARS-CoV-2 positive patients (age ≥18) admitted to the hospital.Main outcome measures 21-day all-cause mortality evaluated by the area under the receiver operator curve (AUC), sensitivity, specificity, positive predictive value and negative predictive value. The predictive value of age was explored by comparison with age-based rules used in practice and by excluding age from the analysis.Results 2273 patients were included, of whom 516 had died or discharged to palliative care within 21 days after admission. Five feature sets, including premorbid, clinical presentation and laboratory and radiology values, were derived from 80 features. Additionally, an Analysis of Variance (ANOVA)-based data-driven feature selection selected the 10 features with the highest F values: age, number of home medications, urea nitrogen, lactate dehydrogenase, albumin, oxygen saturation (%), oxygen saturation is measured on room air, oxygen saturation is measured on oxygen therapy, blood gas pH and history of chronic cardiac disease. A linear logistic regression and non-linear tree-based gradient boosting algorithm fitted the data with an AUC of 0.81 (95% CI 0.77 to 0.85) and 0.82 (0.79 to 0.85), respectively, using the 10 selected features. Both models outperformed age-based decision rules used in practice (AUC of 0.69, 0.65 to 0.74 for age >70). Furthermore, performance remained stable when excluding age as predictor (AUC of 0.78, 0.75 to 0.81).Conclusion Both models showed good performance and had better test characteristics than age-based decision rules, using 10 admission features readily available in Dutch hospitals. The models hold promise to aid decision-making during a hospital bed shortage.
Published: 2021
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17. The characteristics of pallidal low-frequency and beta bursts could help implementing adaptive brain stimulation in the parkinsonian and dystonic internal globus pallidus

Author: Dan Piña-Fuentes, Jonathan C. van Zijl, J. Marc C. van Dijk, Simon Little, Gerd Tinkhauser, D.L. Marinus Oterdoom, Marina A.J. Tijssen, and Martijn Beudel
Subjects: Dystonia, Deep brain stimulation, Neural oscillations, Local field potentials, Closed-loop, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Introduction: Adaptive deep brain stimulation (aDBS) has been applied in Parkinson's disease (PD), based on the presence of brief high-amplitude beta (13–35 Hz) oscillation bursts in the subthalamic nucleus (STN), which correlate with symptom severity. Analogously, average low-frequency (LF) oscillatory power (4–12 Hz) in the internal globus pallidus (GPi) correlates with dystonic symptoms and might be a suitable physiomarker for aDBS in dystonia. Characterization of pallidal bursts could facilitate the implementation of aDBS in the GPi of PD and dystonia patients. Objective and methods: We aimed to describe the bursting behaviour of LF and beta oscillations in a cohort of five GPi-DBS PD patients and compare their amplitude and length with those of a cohort of seven GPi-DBS dystonia, and six STN-DBS PD patients (n electrodes = 34). Furthermore, we used the information obtained to set up aDBS and test it in the GPi of both a dystonia and a PD patient (n = 2), using either LF (dystonia) or beta oscillations (PD) as feedback signals. Results: LF and beta oscillations in the dystonic and parkinsonian GPi occur as phasic, short-lived bursts, similarly to the parkinsonian STN. The amplitude profile of such bursts, however, differed significantly. Dystonia showed higher LF burst amplitudes, while PD presented higher beta burst amplitudes. Burst characteristics in the parkinsonian GPi and STN were similar. Furthermore, aDBS applied in the GPi was feasible and well tolerated in both diseases. Conclusion: Pallidal LF and beta burst amplitudes have different characteristics in PD and dystonia. The presence of increased burst amplitudes could be employed as feedback for GPi-aDBS.
Published: 2019
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18. Clinical features and prognostic factors in Covid-19: A prospective cohort study

Author: Sanne de Bruin, Lieuwe D. Bos, Marian A. van Roon, Anita M. Tuip-de Boer, Alex R. Schuurman, Marleen J.A. Koel-Simmelinck, Harm Jan Bogaard, Pieter Roel Tuinman, Michiel A. van Agtmael, Jörg Hamann, Charlotte E. Teunissen, W. Joost Wiersinga, A.H. (Koos) Zwinderman, Matthijs C. Brouwer, Diederik van de Beek, Alexander P.J. Vlaar, Michiel van Agtmael, Anne Geke Algera, Brent Appelman, Frank van Baarle, Diane Bax, Martijn Beudel, Marije Bomers, Peter Bonta, Lieuwe Bos, Michela Botta, Justin de Brabander, Godelieve de Bree, David T.P. Buis, Marianna Bugiani, Esther Bulle, Osoul Chouchane, Alex Cloherty, Maurits C.F.J. de Rotte, Mirjam Dijkstra, Dave A. Dongelmans, Romein W.G. Dujardin, Paul Elbers, Lucas Fleuren, Suzanne Geerlings, Theo Geijtenbeek, Armand Girbes, Bram Goorhuis, Martin P. Grobusch, Florianne Hafkamp, Laura Hagens, Jorg Hamann, Vanessa Harris, Robert Hemke, Sabine M. Hermans, Leo Heunks, Markus Hollmann, Janneke Horn, Joppe W. Hovius, Menno D. de Jong, Rutger Koning, Endry H.T. Lim, Niels van Mourik, Jeannine Nellen, Esther J. Nossent, Frederique Paulus, Edgar Peters, Dan A.I. Piña-Fuentes, Tom van der Poll, Bennedikt Preckel, Jan M. Prins, Jorinde Raasveld, Tom Reijnders, Michiel Schinkel, Femke A.P. Schrauwen, Marcus J. Schultz, Alex Schuurmans, Jaap Schuurmans, Kim Sigaloff, Marleen A. Slim, Patrick Smeele, Marry Smit, Cornelis S. Stijnis, Willemke Stilma, Charlotte Teunissen, Patrick Thoral, Anissa M. Tsonas, Pieter R. Tuinman, Marc van der Valk, Denise Veelo, Carolien Volleman, Heder de Vries, Lonneke A. Vught, Michèle van Vugt, Dorien Wouters, and A.H (Koos) Zwinderman
Subjects: COVID-19, Prognosis, Biomarker, Pathway analysis, Clinical features, Medicine, Medicine (General), R5-920
Abstract: Background: Mortality rates are high among hospitalized patients with COVID-19, especially in those intubated on the ICU. Insight in pathways associated with unfavourable outcome may lead to new treatment strategies. Methods: We performed a prospective cohort study of patients with COVID-19 admitted to general ward or ICU who underwent serial blood sampling. To provide insight in the pathways involved in disease progression, associations were estimated between outcome risk and serial measurements of 64 biomarkers in potential important pathways of COVID-19 infection (inflammation, tissue damage, complement system, coagulation and fibrinolysis) using joint models combining Cox regression and linear mixed-effects models. For patients admitted to the general ward, the primary outcome was admission to the ICU or mortality (unfavourable outcome). For patients admitted to the ICU, the primary outcome was 12-week mortality. Findings: A total of 219 patients were included: 136 (62%) on the ward and 119 patients (54%) on the ICU; 36 patients (26%) were included in both cohorts because they were transferred from general ward to ICU. On the general ward, 54 of 136 patients (40%) had an unfavourable outcome and 31 (23%) patients died. On the ICU, 54 out of 119 patients (45%) died. Unfavourable outcome on the general ward was associated with changes in concentrations of IL-6, IL-8, IL-10, soluble Receptor for Advanced Glycation End Products (sRAGE), vascular cell adhesion molecule 1 (VCAM-1) and Pentraxin-3. Death on the ICU was associated with changes in IL-6, IL-8, IL-10, sRAGE, VCAM-1, Pentraxin-3, urokinase-type plasminogen activator receptor, IL-1-receptor antagonist, CD14, procalcitonin, tumor necrosis factor alfa, tissue factor, complement component 5a, Growth arrest–specific 6, angiopoietin 2, and lactoferrin. Pathway analysis showed that unfavourable outcome on the ward was mainly driven by chemotaxis and interleukin production, whereas death on ICU was associated with a variety of pathways including chemotaxis, cell-cell adhesion, innate host response mechanisms, including the complement system, viral life cycle regulation, angiogenesis, wound healing and response to corticosteroids. Interpretation: Clinical deterioration in patients with severe COVID-19 involves multiple pathways, including chemotaxis and interleukin production, but also endothelial dysfunction, the complement system, and immunothrombosis. Prognostic markers showed considerable overlap between general ward and ICU patients, but we identified distinct differences between groups that should be considered in the development and timing of interventional therapies in COVID-19. Funding: Amsterdam UMC, Amsterdam UMC Corona Fund, and Dr. C.J. Vaillant Fonds.
Published: 2021
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19. The potential of chronic subcortical recordings for unravelling basal ganglia function and optimisation of deep brain stimulation

Author: Martijn Beudel
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Published: 2021
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20. Can predicting COVID-19 mortality in a European cohort using only demographic and comorbidity data surpass age-based prediction: An externally validated study.

Author: Avishek Chatterjee, Guangyao Wu, Sergey Primakov, Cary Oberije, Henry Woodruff, Pieter Kubben, Ronald Henry, Marcel J H Aries, Martijn Beudel, Peter G Noordzij, Tom Dormans, Niels C Gritters van den Oever, Joop P van den Bergh, Caroline E Wyers, Suat Simsek, Renée Douma, Auke C Reidinga, Martijn D de Kruif, Julien Guiot, Anne-Noelle Frix, Renaud Louis, Michel Moutschen, Pierre Lovinfosse, and Philippe Lambin
Subjects: Medicine, Science
Abstract: ObjectiveTo establish whether one can build a mortality prediction model for COVID-19 patients based solely on demographics and comorbidity data that outperforms age alone. Such a model could be a precursor to implementing smart lockdowns and vaccine distribution strategies.MethodsThe training cohort comprised 2337 COVID-19 inpatients from nine hospitals in The Netherlands. The clinical outcome was death within 21 days of being discharged. The features were derived from electronic health records collected during admission. Three feature selection methods were used: LASSO, univariate using a novel metric, and pairwise (age being half of each pair). 478 patients from Belgium were used to test the model. All modeling attempts were compared against an age-only model.ResultsIn the training cohort, the mortality group's median age was 77 years (interquartile range = 70-83), higher than the non-mortality group (median = 65, IQR = 55-75). The incidence of former/active smokers, male gender, hypertension, diabetes, dementia, cancer, chronic obstructive pulmonary disease, chronic cardiac disease, chronic neurological disease, and chronic kidney disease was higher in the mortality group. All stated differences were statistically significant after Bonferroni correction. LASSO selected eight features, novel univariate chose five, and pairwise chose none. No model was able to surpass an age-only model in the external validation set, where age had an AUC of 0.85 and a balanced accuracy of 0.77.ConclusionWhen applied to an external validation set, we found that an age-only mortality model outperformed all modeling attempts (curated on www.covid19risk.ai) using three feature selection methods on 22 demographic and comorbid features.
Published: 2021
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21. Editorial: The Role of the Basal Ganglia in Somatosensory-Motor Interactions: Evidence From Neurophysiology and Behavior

Author: Martijn Beudel, Antonella Macerollo, Matt J. N. Brown, and Robert Chen
Subjects: basal ganglia, deep brain stimulation, Parkinson's disease, dystonia, oscillations, somatosensory, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Published: 2020
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22. Reversal of Status Dystonicus after Relocation of Pallidal Electrodes in DYT6 Generalized Dystonia

Author: D.L. Marinus Oterdoom, Martje E. van Egmond, Luisa Cassini Ascencao, J. Marc C. van Dijk, Assel Saryyeva, Martijn Beudel, Joachim Runge, Tom J. de Koning, Mahmoud Abdallat, Hendriekje Eggink, Marina A. Tijssen, and Joachim K. Krauss
Subjects: Status dystonicus, Deep brain stimulation, DBS, DYT6, Neurology, Diseases of the musculoskeletal system, RC925-935, Neurology. Diseases of the nervous system, RC346-429
Abstract: Background: DYT6 dystonia can have an unpredictable clinical course and the result of deep brain stimulation (DBS) of the internal part of the globus pallidus (GPi) is known to be less robust than in other forms of autosomal dominant dystonia. Patients who had previous stereotactic surgery with insufficient clinical benefit form a particular challenge with very limited other treatment options available. Case Report: A pediatric DYT6 patient unexpectedly deteriorated to status dystonicus 1 year after GPi DBS implantation with good initial clinical response. After repositioning the DBS electrodes the status dystonicus resolved. Discussion: This case study demonstrates that medication-resistant status dystonicus in DYT6 dystonia can be reversed by relocation of pallidal electrodes. This case highlights that repositioning of DBS electrodes may be considered in patients with status dystonicus, especially when the electrode position is not optimal, even after an initial clinical response to DBS.
Published: 2018
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23. Adaptive deep brain stimulation as advanced Parkinson’s disease treatment (ADAPT study): protocol for a pseudo-randomised clinical study

Author: Dan Piña-Fuentes, Martijn Beudel, Simon Little, D L Marinus Oterdoom, and J Marc C van Dijk
Subjects: Medicine
Abstract: IntroductionAdaptive deep brain stimulation (aDBS), based on the detection of increased beta oscillations in the subthalamic nucleus (STN), has been assessed in patients with Parkinson’s disease (PD) during the immediate postoperative setting. In these studies, aDBS was shown to be at least as effective as conventional DBS (cDBS), while stimulation time and side effects were reduced. However, the effect of aDBS on motor symptoms and stimulation-induced side effects during the chronically implanted phase (after the stun effect of DBS placement has disappeared) has not yet been determined.Methods and analysisThis protocol describes a single-centre clinical study in which aDBS will be tested in 12 patients with PD undergoing battery replacement, with electrodes implanted in the STN, and as a proof of concept in the internal globus pallidus. Patients included will be allocated in a pseudo-randomised fashion to a three-condition (no stimulation/cDBS/ aDBS), cross-over design. A battery of tests will be conducted and recorded during each condition, which aim to measure the severity of motor symptoms and side effects. These tests include a tablet-based tapping test, a subscale of the Movement Disorder Society-unified Parkinson’s disease rating scale (subMDS-UPDRS), the Speech Intelligibility Test (SIT) and a tablet-based version of the Stroop test. SubMDS-UPDRS and SIT recordings will be blindly assessed by independent raters. Data will be analysed using a linear mixed-effects model.Ethics and disseminationThis protocol was approved by the Ethical Committee of the University Medical Centre Groningen, where the study will be carried out. Data management and compliance to research policies and standards of our centre, including data privacy, storage and veracity, will be controlled by an independent monitor. All the scientific findings derived from this protocol are aimed to be made public through publication of articles in international journals.Trial registration numberNTR 5456; Pre-results.
Published: 2019
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24. Linking Pathological Oscillations With Altered Temporal Processing in Parkinsons Disease: Neurophysiological Mechanisms and Implications for Neuromodulation

Author: Martijn Beudel, Anna Sadnicka, Mark Edwards, and Bauke M. de Jong
Subjects: Parkinson's disease, deep brain stimulation, oscillations, timing, movement disorders, Neurology. Diseases of the nervous system, RC346-429
Abstract: Emerging evidence suggests that Parkinson's disease (PD) results from disrupted oscillatory activity in cortico-basal ganglia-thalamo-cortical (CBGTC) and cerebellar networks which can be partially corrected by applying deep brain stimulation (DBS). The inherent dynamic nature of such oscillatory activity might implicate that is represents temporal aspects of motor control. While the timing of muscle activities in CBGTC networks constitute the temporal dimensions of distinct motor acts, these very networks are also involved in somatosensory processing. In this respect, a temporal aspect of somatosensory processing in motor control concerns matching predicted (feedforward) and actual (feedback) sensory consequences of movement which implies a distinct contribution to demarcating the temporal order of events. Emerging evidence shows that such somatosensory processing is altered in movement disorders. This raises the question how disrupted oscillatory activity is related to impaired temporal processing and how/whether DBS can functionally restore this. In this perspective article, the neural underpinnings of temporal processing will be reviewed and translated to the specific alternated oscillatory neural activity specifically found in Parkinson's disease. These findings will be integrated in a neurophysiological framework linking somatosensory and motor processing. Finally, future implications for neuromodulation will be discussed with potential implications for strategy across a range of movement disorders.
Published: 2019
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25. The Inter-rater Variability of Clinical Assessment in Post-anoxic Myoclonus

Author: Jonathan C. van Zijl, Martijn Beudel, Jan-Willem J. Elting, Bauke M. de Jong, Joukje van der Naalt, Walter M. van den Bergh, Andrea O. Rossetti, Marina A. Tijssen, and Janneke Horn
Subjects: Diseases of the musculoskeletal system, RC925-935, Neurology. Diseases of the nervous system, RC346-429
Abstract: Background: Acute post-anoxic myoclonus (PAM) can be divided into an unfavorable (generalized/subcortical) and more favorable ((multi)focal/cortical) outcome group that could support prognostication in post-anoxic encephalopathy; however, the inter-rater variability of clinically assessing these PAM subtypes is unknown. Methods: We prospectively examined PAM patients using a standardized video protocol. Videos were rated by three neurologists who classified PAM phenotype (generalized/(multi)focal), stimulus sensitivity, localization (proximal/distal/both), and severity (Clinical Global Impression-Severity Scale (CGI-S) and Unified Myoclonus Rating Scale (UMRS)). Results: Poor inter-rater agreement was found for phenotype and stimulus sensitivity (κ = –0.05), moderate agreement for localization (κ = 0.46). Substantial agreement was obtained for the CGI-S (intraclass correlation coefficient (ICC) = 0.64) and almost perfect agreement for the UMRS (ICC = 0.82). Discussion: Clinical assessment of PAM is not reproducible between physicians, and should therefore not be used for prognostication. PAM severity measured by the UMRS appears to be reliable; however, the relation between PAM severity and outcome is unknown.
Published: 2017
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26. The Parkinsonian Basal Ganglia Network: Measures of Power, Linear and Non-Linear Synchronization and their Relationship to L-DOPA Treatment and OFF State Motor Severity

Author: Timothy West, Simon Farmer, Luc Berthouze, Ashwani Jha, Martijn Beudel, Thomas Foltynie, Patricia Limousin, Ludvic Zrinzo, Peter Brown, and Vladimir Litvak
Subjects: connectivity, deep brain stimulation (DBS), Metastability, coherence, Long-range temporal correlations, non-linear analysis, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: In this paper we investigated the dopaminergic modulation of neuronal interactions occurring in the subthalamic nucleus (STN) during Parkinson’s disease (PD). We utilized linear measures of local and long range synchrony such as power and coherence, as well as Detrended Fluctuation Analysis for Phase Synchrony (DFA-PS)- a recently developed non-linear method that computes the extent of long tailed autocorrelations present in the phase interactions between two coupled signals. Through analysis of local field potentials (LFPs) taken from the STN we seek to determine changes in the neurodynamics that may underpin the pathophysiology of PD in a group of 12 patients who had undergone surgery for deep brain stimulation. We demonstrate up modulation of alpha-theta (5-12 Hz) band power in response to L-DOPA treatment, whilst low beta band power (15-20 Hz) band-power is suppressed. We also find evidence for significant local connectivity within the region surrounding STN although there was no evidence for modulation via administration of L-DOPA. Further to this we present evidence for a positive correlation between the phase ordering of bilateral STN interactions and the severity of bradykinetic and rigidity symptoms in PD. Although the ability of non-linear measures to predict clinical state did not exceed standard measures such as beta power, these measures may help identify the connections which play a role in pathological dynamics.
Published: 2016
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27. The Effect of Visual Feedback on Writing Size in Parkinson’s Disease

Author: Adriaan R. E. Potgieser, Elizabeth Roosma, Martijn Beudel, and Bauke M. de Jong
Subjects: Neurology. Diseases of the nervous system, RC346-429
Abstract: Parkinson’s disease (PD) leads to impairment in multiple cognitive domains. Micrographia is a relatively early PD sign of visuomotor dysfunction, characterized by a global reduction in writing size and a decrement in size during writing. Here we aimed to investigate the effect of withdrawal of visual feedback on writing size in patients with PD. Twenty-five patients with non-tremor-dominant PD without cognitive dysfunction and twenty-five age-matched controls had to write a standard sentence with and without visual feedback. We assessed the effect of withdrawal of visual feedback by measuring vertical word size (i), horizontal length of the sentence (ii), and the summed horizontal word length without interspacing (iii), comparing patients with controls. In both patients and controls, writing was significantly larger without visual feedback. This enlargement did not significantly differ between the groups. Smaller handwriting significantly correlated with increased disease severity. Contrary to previous observations that withdrawal of visual feedback caused increased writing size in specifically PD, we did not find differences between patients and controls. Both groups wrote larger without visual feedback, which adds insight in general neuronal mechanisms underlying the balance between feed-forward and feedback in visuomotor control, mechanisms that also hold for grasping movements.
Published: 2015
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28. Chronic Adaptive DBS Provides Similar “On” Time with Trend of Improvement Compared to Continuous DBS in Parkinson’s Disease and 98% of Participants Chose to Remain on aDBS (S2.008)

Author: Bronte-Stewart, Helen, primary, Martijn, Beudel, additional, Ostrem, Jill, additional, Little, Simon, additional, Almeida, Leonardo, additional, Zamora, Adolfo Ramirez, additional, Fasano, Alfonso, additional, Hassell, Travis, additional, Mitchell, Kyle, additional, Moro, Elena, additional, Gostkowski, Michal, additional, Sarangmat, Nagaraja, additional, Stanslaski, Scott, additional, Tonder, Lisa, additional, Tan, Ye, additional, Goble, Tim, additional, Summers, Rebekah, additional, Raike, Robert, additional, and Herrington, Todd, additional
Published: 2024
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29. A Clinical Applicable Smartwatch Application for Measuring Hyperkinetic Movement Disorder Severity.

Author: M. Vochteloo, Marina A. J. Tijssen, and Martijn Beudel
Published: 2019
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30. A method for automatic, objective and continuous scoring of bradykinesia.

Author: Octavio Martinez Manzanera, E. Roosma, Martijn Beudel, R. W. K. Borgemeester, Teus van Laar, and Natasha M. Maurits
Published: 2015
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31. Imaging Dopaminergic Neurotransmission in Neurodegenerative Disorders

Author: Elon D, Wallert, Elsmarieke, van de Giessen, Remco J J, Knol, Martijn, Beudel, Rob M A, de Bie, Jan, Booij, Graduate School, Radiology and Nuclear Medicine, ANS - Brain Imaging, Neurology, ANS - Neurodegeneration, ANS - Compulsivity, Impulsivity & Attention, APH - Aging & Later Life, and Radiology and nuclear medicine
Subjects: Diagnostic Imaging, Lewy Body Disease, neurodegeneration, PET, SPECT, Neurodegenerative Diseases, Parkinson Disease, Synaptic Transmission, PET, Parkinsonian Disorders, SPECT, Humans, Radiology, Nuclear Medicine and imaging, Parkinson, dopamine
Abstract: Imaging of dopaminergic transmission in neurodegenerative disorders such as Parkinson disease (PD) or dementia with Lewy bodies plays a major role in clinical practice and in clinical research. We here review the role of imaging of the nigrostriatal pathway, as well as of striatal receptors and dopamine release, in common neurodegenerative disorders in clinical practice and research. Imaging of the nigrostriatal pathway has a high diagnostic accuracy to detect nigrostriatal degeneration in disorders characterized by nigrostriatal degeneration, such as PD and dementia with Lewy bodies, and disorders of more clinical importance, namely in patients with clinically uncertain parkinsonism. Imaging of striatal dopamine D2/3 receptors is not recommended for the differential diagnosis of parkinsonian disorders in clinical practice anymore. Regarding research, recently the European Medicines Agency has qualified dopamine transporter imaging as an enrichment biomarker for clinical trials in early PD, which underlines the high diagnostic accuracy of this imaging tool and will be implemented in future trials. Also, imaging of the presynaptic dopaminergic system plays a major role in, for example, examining the extent of nigrostriatal degeneration in preclinical and premotor phases of neurodegenerative disorders and to examine subtypes of PD. Also, imaging of postsynaptic dopamine D2/3 receptors plays a role in studying, for example, the neuronal substrate of impulse control disorders in PD, as well as in measuring endogenous dopamine release to examine, for example, motor complications in the treatment of PD. Finally, novel MRI sequences as neuromelanin-sensitive MRI are promising new tools to study nigrostriatal degeneration in vivo.
Published: 2022

32. Employing LFP Recording to Optimize Stimulation Location and Amplitude in Chronic DBS for Parkinson’s Disease: A Proof-of-concept Pilot Study

Author: Bart E.K.S. Swinnen, Mariëlle J. Stam, Arthur W.G. Buijink, Martijn G.J. de Neeling, Peter R. Schuurman, Rob M.A. de Bie, and Martijn Beudel
Published: 2023

33. Adaptive DBS Algorithm for Personalized Therapy in Parkinson’s Disease: ADAPT-PD clinical trial methodology and early data (P1-11.002)

Author: Helen Bronte-Stewart, Martijn Beudel, Jill L. Ostrem, Alfonso Fasano, Leonardo Almeida, Travis Hassell, Elena Moro, Michal Gostkowski, Kyle T. Mitchell, Elodie Hainque, Nagaraja Sarangmat, Scott Stanslaski, Lisa Tonder, Rebekah Summers, Robert S. Raike, and Todd M. Herrington
Published: 2023

34. Procalcitonin-Guided Antibiotic Prescription in Patients With COVID-19

Author: Lisa Hessels, Esther Speksnijder, Nienke Paternotte, Astrid van Huisstede, Willemien Thijs, Margot Scheer, Mariëlle van der Steen-Dieperink, Lieve Knarren, Joop P. van Den Bergh, Kristien Winckers, Ronald Henry, Suat Simsek, Wim G. Boersma, Brent Appelman, Michiel Schinkel, David Buis, Kim C.E. Sigalof, Paul W.G. Elbers, Daisy Rusch, Auke Reidinga, Hazra Moeniralam, Caroline Wyers, Joop van den Bergh, Bastiaan van Dam, Niels C. van den Gritters, Nejma Bokhizzou, Kees Brinkman, Martijn de Kruif, Tom Dormans, Renée Douma, Lianne R. de Haan, Tsz Yeung Fung, and Martijn Beudel
Subjects: Pulmonary and Respiratory Medicine, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine
Published: 2023

35. Lipoprotein(a), venous thromboembolism and COVID-19

Author: Nick S. Nurmohamed, Didier Collard, Laurens F. Reeskamp, Yannick Kaiser, Jeffrey Kroon, Tycho R. Tromp, Bert-Jan H. van den Born, Michiel Coppens, Alexander P.J. Vlaar, Martijn Beudel, Diederik van de Beek, Nick van Es, Patrick M. Moriarty, Sotirios Tsimikas, Erik S.G. Stroes, Cardiology, Internal medicine, Neurology, ACS - Atherosclerosis & ischemic syndromes, ACS - Diabetes & metabolism, ACS - Pulmonary hypertension & thrombosis, Graduate School, Vascular Medicine, Experimental Vascular Medicine, ACS - Microcirculation, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Public and occupational health, APH - Personalized Medicine, APH - Global Health, ACS - Heart failure & arrhythmias, AII - Inflammatory diseases, Intensive Care Medicine, ANS - Neurodegeneration, and ANS - Neuroinfection & -inflammation
Subjects: IL-6, Risk Factors, SARS-CoV-2, Humans, COVID-19, Pilot Projects, Venous Thromboembolism, VTE, Cardiology and Cardiovascular Medicine, Article, Lipoprotein(a)
Abstract: Background and aims Thrombosis is a major driver of adverse outcome and mortality in patients with Coronavirus disease 2019 (COVID-19). Hypercoagulability may be related to the cytokine storm associated with COVID-19, which is mainly driven by interleukin (IL)-6. Plasma lipoprotein(a) [Lp(a)] levels increase following IL-6 upregulation and Lp(a) has anti-fibrinolytic properties. This study investigated whether Lp(a) elevation may contribute to the pro-thrombotic state hallmarking COVID-19 patients. Methods Lp(a), IL-6 and C-reactive protein (CRP) levels were measured in 219 hospitalized patients with COVID-19 and analyzed with linear mixed effects model. The baseline biomarkers and increases during admission were related to venous thromboembolism (VTE) incidence and clinical outcomes in a Kaplan-Meier and logistic regression analysis. Results Lp(a) levels increased significantly by a mean of 16.9 mg/dl in patients with COVID-19 during the first 21 days after admission. Serial Lp(a) measurements were available in 146 patients. In the top tertile of Lp(a) increase, 56.2% of COVID-19 patients experienced a VTE event compared to 18.4% in the lowest tertile (RR 3.06, 95% CI 1.61–5.81; p, Graphical abstract Image 1
Published: 2022

36. A systematic review of local field potential physiomarkers in Parkinson's disease: from clinical correlations to adaptive deep brain stimulation algorithms

Author: Bernadette C. M. van Wijk, Rob M. A. de Bie, Martijn Beudel, Coordination Dynamics, IBBA, AMS - Rehabilitation & Development, Neurology, and ANS - Neurodegeneration
Subjects: Electrophysiology, Neurology, SDG 3 - Good Health and Well-being, Deep brain stimulation, Parkinson’s disease, Neurology (clinical), Beta oscillations, Subthalamic nucleus
Abstract: Deep brain stimulation (DBS) treatment has proven effective in suppressing symptoms of rigidity, bradykinesia, and tremor in Parkinson’s disease. Still, patients may suffer from disabling fluctuations in motor and non-motor symptom severity during the day. Conventional DBS treatment consists of continuous stimulation but can potentially be further optimised by adapting stimulation settings to the presence or absence of symptoms through closed-loop control. This critically relies on the use of ‘physiomarkers’ extracted from (neuro)physiological signals. Ideal physiomarkers for adaptive DBS (aDBS) are indicative of symptom severity, detectable in every patient, and technically suitable for implementation. In the last decades, much effort has been put into the detection of local field potential (LFP) physiomarkers and in their use in clinical practice. We conducted a research synthesis of the correlations that have been reported between LFP signal features and one or more specific PD motor symptoms. Features based on the spectral beta band (~ 13 to 30 Hz) explained ~ 17% of individual variability in bradykinesia and rigidity symptom severity. Limitations of beta band oscillations as physiomarker are discussed, and strategies for further improvement of aDBS are explored.
Published: 2023

37. Predicting responders to prone positioning in mechanically ventilated patients with COVID-19 using machine learning

Author: Tariq A, Dam, Luca F, Roggeveen, Fuda, van Diggelen, Lucas M, Fleuren, Ameet R, Jagesar, Martijn, Otten, Heder J, de Vries, Diederik, Gommers, Olaf L, Cremer, Rob J, Bosman, Sander, Rigter, Evert-Jan, Wils, Tim, Frenzel, Dave A, Dongelmans, Remko, de Jong, Marco A A, Peters, Marlijn J A, Kamps, Dharmanand, Ramnarain, Ralph, Nowitzky, Fleur G C A, Nooteboom, Wouter, de Ruijter, Louise C, Urlings-Strop, Ellen G M, Smit, D Jannet, Mehagnoul-Schipper, Tom, Dormans, Cornelis P C, de Jager, Stefaan H A, Hendriks, Sefanja, Achterberg, Evelien, Oostdijk, Auke C, Reidinga, Barbara, Festen-Spanjer, Gert B, Brunnekreef, Alexander D, Cornet, Walter, van den Tempel, Age D, Boelens, Peter, Koetsier, Judith, Lens, Harald J, Faber, A, Karakus, Robert, Entjes, Paul, de Jong, Thijs C D, Rettig, Sesmu, Arbous, Sebastiaan J J, Vonk, Tomas, Machado, Willem E, Herter, Harm-Jan, de Grooth, Patrick J, Thoral, Armand R J, Girbes, Mark, Hoogendoorn, Paul W G, Elbers, Martijn, Beudel, Intensive Care, Artificial intelligence, Network Institute, Artificial Intelligence (section level), Computational Intelligence, Mathematics, Intensive care medicine, ACS - Microcirculation, Amsterdam Cardiovascular Sciences, ACS - Diabetes & metabolism, AII - Infectious diseases, Internal medicine, Epidemiology and Data Science, and APH - Methodology
Subjects: All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, Other Research Radboud Institute for Health Sciences [Radboudumc 0], Critical Care and Intensive Care Medicine
Abstract: Background For mechanically ventilated critically ill COVID-19 patients, prone positioning has quickly become an important treatment strategy, however, prone positioning is labor intensive and comes with potential adverse effects. Therefore, identifying which critically ill intubated COVID-19 patients will benefit may help allocate labor resources. Methods From the multi-center Dutch Data Warehouse of COVID-19 ICU patients from 25 hospitals, we selected all 3619 episodes of prone positioning in 1142 invasively mechanically ventilated patients. We excluded episodes longer than 24 h. Berlin ARDS criteria were not formally documented. We used supervised machine learning algorithms Logistic Regression, Random Forest, Naive Bayes, K-Nearest Neighbors, Support Vector Machine and Extreme Gradient Boosting on readily available and clinically relevant features to predict success of prone positioning after 4 h (window of 1 to 7 h) based on various possible outcomes. These outcomes were defined as improvements of at least 10% in PaO2/FiO2 ratio, ventilatory ratio, respiratory system compliance, or mechanical power. Separate models were created for each of these outcomes. Re-supination within 4 h after pronation was labeled as failure. We also developed models using a 20 mmHg improvement cut-off for PaO2/FiO2 ratio and using a combined outcome parameter. For all models, we evaluated feature importance expressed as contribution to predictive performance based on their relative ranking. Results The median duration of prone episodes was 17 h (11–20, median and IQR, N = 2632). Despite extensive modeling using a plethora of machine learning techniques and a large number of potentially clinically relevant features, discrimination between responders and non-responders remained poor with an area under the receiver operator characteristic curve of 0.62 for PaO2/FiO2 ratio using Logistic Regression, Random Forest and XGBoost. Feature importance was inconsistent between models for different outcomes. Notably, not even being a previous responder to prone positioning, or PEEP-levels before prone positioning, provided any meaningful contribution to predicting a successful next proning episode. Conclusions In mechanically ventilated COVID-19 patients, predicting the success of prone positioning using clinically relevant and readily available parameters from electronic health records is currently not feasible. Given the current evidence base, a liberal approach to proning in all patients with severe COVID-19 ARDS is therefore justified and in particular regardless of previous results of proning.
Published: 2022

38. Progressive Multifocal Leukoencephalopathy Treated by Immune Checkpoint Inhibitors

Author: Xavier, Boumaza, Baptiste, Bonneau, Damien, Roos-Weil, Carmela, Pinnetti, Sebastian, Rauer, Louisa, Nitsch, Arnaud, Del Bello, Ilijas, Jelcic, Kurt-Wolfram, Sühs, Jacques, Gasnault, Yasemin, Goreci, Oliver, Grauer, Sharmilee, Gnanapavan, Rebecca, Wicklein, Nicolas, Lambert, Thomas, Perpoint, Martijn, Beudel, David, Clifford, Agnès, Sommet, Irene, Cortese, and Guillaume, Martin-Blondel
Subjects: Neurology, Neurology (clinical)
Abstract: Our aim was to assess the real-world effectiveness of immune checkpoint inhibitors for treatment of patients with progressive multifocal leukoencephalopathy (PML).We conducted a multicenter survey compiling retrospective data from 79 PML patients, including 38 published cases and 41 unpublished cases, who received immune checkpoint inhibitors as add-on to standard of care. One-year follow-up data were analyzed to determine clinical outcomes and safety profile. Logistic regression was used to identify variables associated with 1-year survival.Predisposing conditions included hematological malignancy (n = 38, 48.1%), primary immunodeficiency (n = 14, 17.7%), human immunodeficiency virus/acquired immunodeficiency syndrome (n = 12, 15.2%), inflammatory disease (n = 8, 10.1%), neoplasm (n = 5, 6.3%), and transplantation (n = 2, 2.5%). Pembrolizumab was most commonly used (n = 53, 67.1%). One-year survival was 51.9% (41/79). PML-immune reconstitution inflammatory syndrome (IRIS) was reported in 15 of 79 patients (19%). Pretreatment expression of programmed cell death-1 on circulating T cells did not differ between survivors and nonsurvivors. Development of contrast enhancement on follow-up magnetic resonance imaging at least once during follow-up (OR = 3.16, 95% confidence interval = 1.20-8.72, p = 0.02) was associated with 1-year survival. Cerebrospinal fluid JC polyomavirus DNA load decreased significantly by 1-month follow-up in survivors compared to nonsurvivors (p 0.0001). Thirty-two adverse events occurred among 24 of 79 patients (30.4%), and led to treatment discontinuation in 7 of 24 patients (29.1%).In this noncontrolled retrospective study of patients with PML who were treated with immune checkpoint inhibitors, mortality remains high. Development of inflammatory features or overt PML-IRIS was commonly observed. This study highlights that use of immune checkpoint inhibitors should be strictly personalized toward characteristics of the individual PML patient. ANN NEUROL 2022.
Published: 2022

39. Intramuscular adipose tissue at level Th12 is associated with survival in COVID-19

Author: Lieuwe Bos, Diederik Van de Beek, Ludo Beenen, Denise Veelo, Joost Raaphorst, Benedikt Preckel, Jan Prins, Marije Bomers, Willem Wiersinga, Minoesch Min, Matthijs Brouwer, Martijn Beudel, Alexander Vlaar, Harm Jan Bogaard, Neurology, ANS - Neurodegeneration, ANS - Neuroinfection & -inflammation, Graduate School, Radiology and Nuclear Medicine, ACS - Microcirculation, ACS - Pulmonary hypertension & thrombosis, ANS - Neurovascular Disorders, Intensive Care Medicine, AMS - Musculoskeletal Health, AMS - Sports, EURO-NMD, Radiology and nuclear medicine, Intensive care medicine, Internal medicine, AII - Infectious diseases, Pulmonary medicine, Pathology, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Neuroscience - Complex Trait Genetics, ACS - Diabetes & metabolism, Medical Microbiology and Infection Prevention, AMS - Rehabilitation & Development, VU University medical center, Clinical chemistry, Amsterdam Neuroscience - Neurodegeneration, Amsterdam Neuroscience - Neuroinfection & -inflammation, Amsterdam Reproduction & Development (AR&D), APH - Quality of Care, and ACS - Heart failure & arrhythmias
Subjects: 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), QM1-695, MEDLINE, Adipose tissue, Diseases of the musculoskeletal system, Bioinformatics, SARCOPENIA, Text mining, RC925-935, Physiology (medical), Human anatomy, Medicine, SKELETAL-MUSCLE, Orthopedics and Sports Medicine, business, Letter to the Editor
Published: 2021

40. Treat by Suggestion: The Potential Use of N = 1 Trials in Functional Neurological Disorders

Author: Merve Ulubas, Jeannette Gelauff, Martijn Beudel, Neurology, and Amsterdam Neuroscience - Neurodegeneration
Subjects: Neurology, N = 1 trial, functional neurological disorders, placebo controlled trial, Neurology (clinical)
Published: 2022

41. A systematic review of local field potential physiomarkers in Parkinson's disease: from clinical correlations to adaptive deep brain stimulation algorithms

Author: Bernadette C M, van Wijk, Rob M A, de Bie, and Martijn, Beudel
Abstract: Deep brain stimulation (DBS) treatment has proven effective in suppressing symptoms of rigidity, bradykinesia, and tremor in Parkinson's disease. Still, patients may suffer from disabling fluctuations in motor and non-motor symptom severity during the day. Conventional DBS treatment consists of continuous stimulation but can potentially be further optimised by adapting stimulation settings to the presence or absence of symptoms through closed-loop control. This critically relies on the use of 'physiomarkers' extracted from (neuro)physiological signals. Ideal physiomarkers for adaptive DBS (aDBS) are indicative of symptom severity, detectable in every patient, and technically suitable for implementation. In the last decades, much effort has been put into the detection of local field potential (LFP) physiomarkers and in their use in clinical practice. We conducted a research synthesis of the correlations that have been reported between LFP signal features and one or more specific PD motor symptoms. Features based on the spectral beta band (~ 13 to 30 Hz) explained ~ 17% of individual variability in bradykinesia and rigidity symptom severity. Limitations of beta band oscillations as physiomarker are discussed, and strategies for further improvement of aDBS are explored.
Published: 2022

42. Comparison of [

Author: Elon, Wallert, Erwann, Letort, Friso, van der Zant, Ania, Winogrodzka, Henk, Berendse, Martijn, Beudel, Rob, de Bie, Jan, Booij, Pieter, Raijmakers, and Elsmarieke, van de Giessen
Abstract: Two commonly used imaging techniques to aid in the diagnosis of neurodegenerative parkinsonian syndromes are dopamine transporter (DAT) imaging with [We present 11 patients with a clinically uncertain parkinsonian syndrome (CUPS), who received both FDOPA-PET and DAT-SPECT. All patients received an FDOPA-PET scan and DAT-SPECT as part of routine clinical care.The median time between the F-DOPA-PET scan and DAT-SPECT scan was 6 months (range 0-15 months). There was a discrepancy in the reported results of the FDOPA-PET and DAT-SPECT scans in nine patients, including 7 patients whose FDOPA-PET scan was reportedly normal, whereas their DAT-SPECT scan was abnormal.In this case series of CUPS patients, DAT-SPECT was more often rated as abnormal than FDOPA-PET. The striatal loss of FDOPA uptake can be less pronounced than that of DAT binding in CUPS patients in early disease stages. Consequently, the interpretation of FDOPA-PET scans in CUPS can sometimes be challenging in routine practice.
Published: 2022

43. Ethnic Differences in Coronavirus Disease 2019 Hospitalization and Hospital Outcomes in a Multiethnic Population in the Netherlands

Author: Didier Collard, Karien Stronks, Vanessa Harris, Liza Coyer, Kees Brinkman, Martijn Beudel, Nejma Bokhizzou, Renee A Douma, Paul Elbers, Henrike Galenkamp, Marije ten Wolde, Maria Prins, Bert Jan H van den Born, Charles Agyemang, VU University medical center, Intensive care medicine, ACS - Diabetes & metabolism, ACS - Atherosclerosis & ischemic syndromes, Vascular Medicine, Public and occupational health, APH - Health Behaviors & Chronic Diseases, APH - Methodology, Global Health, Infectious diseases, APH - Global Health, AII - Amsterdam institute for Infection and Immunity, Graduate School, AII - Infectious diseases, Neurology, ANS - Neurodegeneration, APH - Personalized Medicine, and ACS - Heart failure & arrhythmias
Subjects: Infectious Diseases, ethnic inequalities, migrants health, Oncology, COVID-19, The Netherlands, outcomes, hospitalization
Abstract: Background Evidence from the United States and United Kingdom suggests that ethnic minority populations are at an increased risk for developing severe coronavirus disease 2019 (COVID-19); however, data from other West-European countries are scarce. Methods We analyzed data from 1439 patients admitted between February 2020 and January 2021 to 4 main hospitals in Amsterdam and Almere, the Netherlands. Differences in the risk for hospitalization were assessed by comparing demographics to the general population. Using a population-based cohort as reference, we determined differences in the association between comorbidities and COVID-19 hospitalization. Outcomes after hospitalization were analyzed using Cox regression. Results The hospitalization risk was higher in all ethnic minority groups than in those of Dutch origin, with age-adjusted odds ratios ranging from 2.2 (95% confidence interval [CI], 1.7–2.6) in Moroccans to 4.5 (95% CI, 3.2–6.0) in Ghanaians. Hypertension and diabetes were similarly associated with COVID-19 hospitalization. For all other comorbidities, we found differential associations. Intensive care unit admission and mortality during 21-day follow-up after hospitalization was comparable between ethnicities. Conclusions The risk of COVID-19 hospitalization was higher in all ethnic minority groups compared to the Dutch, but the risk of adverse outcomes after hospitalization was similar. Our results suggest that these inequalities may in part be attributable to comorbidities that can be prevented by targeted public health prevention measures. More work is needed to gain insight into the role of other potential factors such as social determinants of health, which might have contributed to the ethnic inequalities in COVID-19 hospitalization.
Published: 2022

44. Low-frequency oscillation suppression in dystonia: Implications for adaptive deep brain stimulation

Author: Marina A. J. Tijssen, Martijn Beudel, Dan Piña-Fuentes, D L M Oterdoom, M. E. van Egmond, J. C. van Zijl, J M C van Dijk, Neurology, ANS - Neurodegeneration, and Movement Disorder (MD)
Subjects: Male, 0301 basic medicine, Acute effects, Deep brain stimulation, Deep Brain Stimulation, medicine.medical_treatment, Stimulation, Globus Pallidus, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, In patient, Closed-loop, Adaptive deep brain stimulation, Aged, Aged, 80 and over, Dystonia, Internal globus pallidus, Local field potentials, business.industry, Middle Aged, medicine.disease, Brain Waves, Low-frequency oscillations, 030104 developmental biology, Neurology, Dystonic Disorders, Anesthesia, Female, Neurology (clinical), Geriatrics and Gerontology, Low-frequency oscillation, business, Closed loop, 030217 neurology & neurosurgery
Abstract: BACKGROUND: Low-frequency oscillations (LFO) detected in the internal globus pallidus of dystonia patients have been identified as a physiomarker for adaptive Deep Brain Stimulation (aDBS), since LFO correlate with dystonic symptoms and are rapidly suppressed by continuous DBS (cDBS). However, it is as yet unclear how LFO should be incorporated as feedback for aDBS.OBJECTIVES: to test the acute effects of aDBS, using the amplitude of short-lived LFO-bursts to titrate stimulation, to explore the immediate effects of cDBS on LFO-modulation and dystonic symptoms, and to investigate whether a difference in the resting-state LFO is present between DBS-naïve patients and patients with chronic DBS.METHODS: seven patients were assessed during either DBS-implantation (n = 2) or battery replacement surgery (n = 5), and pseudorandomized in three conditions: no stimulation, cDBS, and aDBS. Additionally, resting-state LFP-recordings from patients undergoing battery replacement were compared to those obtained during DBS-implantation; LFP-recordings from a previous cohort of six dystonia patients undergoing DBS-implantation were incorporated into this analysis (total n = 8 newly implanted patients).RESULTS: we corroborated that a mild LFO-suppression rapidly occurs during cDBS. However, no acute changes in clinical symptoms were observed after cDBS or aDBS. Remarkably, we observed that resting-state LFO were significantly lower in patients who had been effectively treated with chronic cDBS compared to those of newly implanted patients, even when stimulation was suspended.CONCLUSIONS: our results indicate that LFO-suppression in dystonia, similar to symptom response to cDBS, might be gradual, and remain after stimulation is suspended. Therefore, tracking gradual changes in LFO may be required for aDBS implementation.
Published: 2020

45. The Fast Gray Matter Acquisition T1 Inversion Recovery Sequence in Deep Brain Stimulation:Introducing the Rubral Wing for Dentato-Rubro-Thalamic Tract Depiction and Tremor Control

Author: Maarten Bot, Rik Pauwels, Pepijn van den Munckhof, Maartje de Win, Vincent J.J. Odekerken, Martijn Beudel, Joke Dijk, Rob M.A. de Bie, P. Richard Schuurman, Neurosurgery, Radiology and nuclear medicine, and Neurology
Subjects: Anesthesiology and Pain Medicine, Neurology, Neurology (clinical), General Medicine
Abstract: Background: The dentato-rubro-thalamic tract (DRT) is currently considered as a potential target in deep brain stimulation (DBS) for various types of tremor. However, tractography depiction can vary depending on the included brain regions. The fast gray matter acquisition T1 inversion recovery (FGATIR) sequence, with excellent delineation of gray and white matter, possibly provides anatomical identification of rubro-thalamic DRT fibers. Objective: This study aimed to evaluate the FGATIR sequence by comparison with DRT depiction, electrode localization, and effectiveness of DBS therapy. Materials and Methods: In patients with DBS therapy because of medication-refractory tremor, the FGATIR sequence was evaluated for depiction of the thalamus, red nucleus (RN), and rubro-thalamic connections. Deterministic tractography of the DRT, electrode localization, and tremor control were compared. The essential tremor rating scale was used to assess (hand) tremor. Tremor control was considered successful when complete tremor suppression (grade 0) or almost complete suppression (grade 1) was observed. Results: In the postoperative phase, we evaluated 14 patients who underwent DRT-guided DBS: 12 patients with essential tremor, one with tremor-dominant Parkinson disease, and one with multiple sclerosis, representing 24 trajectories. Mean follow-up was 11.3 months (range 6–19 months). The FGATIR sequence provided a clear delineation of a hypointense white matter tract within the hyperintense thalamus. In coronal plane, this tract was most readily recognizable as a “rubral wing,” with the round RN as base and lateral triangular convergence. The deterministic DRT depiction was consistently situated within the rubral wing. The number of active contacts located within the DRT (and rubral wing) was 22 (92%), of which 16 (73%) showed successful tremor control. Conclusions: The FGATIR sequence offers visualization of the rubro-thalamic connections that form the DRT, most readily recognizable as a “rubral wing” in coronal plane. This sequence contributes to tractographic depiction of DRT and provides a direct anatomical DBS target area for tremor control.
Published: 2022

46. Indoleamine 2,3-dioxygenase (IDO)-1 and IDO-2 activity and severe course of COVID-19

Author: René Lutter, Dorien Wouters, A H Koos Zwinderman, Markus Hollmann, Esther J. Nossent, Jorinde Raasveld, Bram Goorhuis, Syun-Ru Yeh, Kim C. E. Sigaloff, Michiel A. van Agtmael, Lieuwe D. J. Bos, Martin P. Grobusch, Michèle van Vugt, Anissa Tsonas, Leo Heunks, Marije K. Bomers, Michela Botta, Frederique Paulus, Joppe W. Hovius, Menno D. de Jong, Suzanne Geerlings, Zachary Geeraerts, Carolien Volleman, Jaap Schuurmans, Jeannine Nellen, Dan A.I. Piña-Fuentes, Edgar Peters, Frédéric M. Vaz, Vanessa Harris, Heder de Vries, Patrick Thoral, Jörg Hamann, Anne Geke Algera, Romein W.G. Dujardin, Laura Hagens, Femke A.P. Schrauwen, Lucas Fleuren, Bennedikt Preckel, Paul Elbers, Rutger Koning, Jan M. Prins, Tom Reijnders, Marry Smit, Alex Cloherty, Justin de Brabander, Harm Jan Bogaard, Eva Roos, Alexander P.J. Vlaar, Armand Girbes, Matthijs C. Brouwer, Cornelis S. Stijnis, Tom van der Poll, Brent Appelman, Theo Geijtenbeek, Diane Bax, Florianne Hafkamp, Anissa M. Tsonas, Michiel Schinkel, Charlotte E. Teunissen, Robert Hemke, Annemiek Dijkhuis, Frank van Baarle, Alex Schuurmans, Paul van der Valk, Buis T P David, Lonneke A. Vught, Marc van der Valk, Peter Bonta, Janneke Horn, Bernadette Schurink, Maurits C.F.J. de Rotte, Sanne de Bruin, Esther Bulle, Endry H.T. Lim, Denise Veelo, Lihui Guo, Marcus J. Schultz, Marleen A. Slim, Sabine M. Hermans, Martijn Beudel, Marianna Bugiani, JanWillem Duitman, Lonneke A. van Vught, W. Joost Wiersinga, Godelieve J. de Bree, Niels van Mourik, Mirjam Dijkstra, Dave A. Dongelmans, Osoul Chouchane, Diederik van de Beek, Willemke Stilma, Pathology, Pulmonary medicine, Amsterdam Neuroscience - Neuroinfection & -inflammation, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Neuroscience - Complex Trait Genetics, Internal medicine, AII - Infectious diseases, Intensive care medicine, Neurology, ACS - Pulmonary hypertension & thrombosis, Laboratory Medicine, Amsterdam Cardiovascular Sciences, ACS - Diabetes & metabolism, Radiology and nuclear medicine, Anesthesiology, Medical Microbiology and Infection Prevention, AMS - Rehabilitation & Development, VU University medical center, Amsterdam Neuroscience - Neurodegeneration, Amsterdam Reproduction & Development (AR&D), Graduate School, Pulmonology, Intensive Care Medicine, ACS - Microcirculation, Vascular Medicine, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Laboratory Genetic Metabolic Diseases, Experimental Immunology, APH - Personalized Medicine, Center of Experimental and Molecular Medicine, ANS - Neurodegeneration, Laboratory for General Clinical Chemistry, Genetic Metabolic Diseases, APH - Quality of Care, Infectious diseases, APH - Global Health, Global Health, APH - Health Behaviors & Chronic Diseases, AII - Amsterdam institute for Infection and Immunity, Radiology and Nuclear Medicine, AMS - Sports, AMS - Musculoskeletal Health, APH - Methodology, ACS - Heart failure & arrhythmias, ANS - Neuroinfection & -inflammation, Nursing, APH - Digital Health, and APH - Aging & Later Life
Subjects: Adult, Programmed cell death, Cell, 3-Hydroxyanthranilic Acid, Apoptosis, Severity of Illness Index, Pathology and Forensic Medicine, chemistry.chemical_compound, Medicine, Humans, Indoleamine-Pyrrole 2,3,-Dioxygenase, Prospective Studies, Receptor, Indoleamine 2,3-dioxygenase, Lung, Kynurenine, Aged, business.industry, Myocardium, Tryptophan, Brain, COVID-19, Middle Aged, Quinolinic Acid, medicine.anatomical_structure, chemistry, Immunology, Autopsy, business, Quinolinic acid, Hormone
Abstract: COVID-19 is a pandemic with high morbidity and mortality. In an autopsy cohort of COVID-19 patients, we found extensive accumulation of the tryptophan degradation products 3-hydroxy-anthranilic acid and quinolinic acid in the lungs, heart, and brain. This was not related to the expression of the tryptophan-catabolizing indoleamine 2,3-dioxygenase (IDO)-1, but rather to that of its isoform IDO-2, which otherwise is expressed rarely. Bioavailability of tryptophan is an absolute requirement for proper cell functioning and synthesis of hormones, whereas its degradation products can cause cell death. Markers of apoptosis and severe cellular stress were associated with IDO-2 expression in large areas of lung and heart tissue, whereas affected areas in brain were more restricted. Analyses of tissue, cerebrospinal fluid, and sequential plasma samples indicate early initiation of the kynurenine/aryl-hydrocarbon receptor/IDO-2 axis as a positive feedback loop, potentially leading to severe COVID-19 pathology. © 2021 The Authors. The Journal of Pathology published by John WileySons, Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Published: 2021

47. The Dutch Data Warehouse, a multicenter and full-admission electronic health records database for critically ill COVID-19 patients

Author: Roberto Noorduijn-Londono, Sander Rigter, Willem E. Herter, Tomas Machado, Gert B. Brunnekreef, Thijs C. D. Rettig, Evert-Jan Wils, Remko de Jong, S Arbous, Harald J. Faber, Cornelis P.C. de Jager, Paul de Jong, Auke C Reidinga, Sebastiaan J. J. Vonk, Dave A. Dongelmans, Wouter de Ruijter, Taco Houwert, Ralph Nowitzky, Daan P de Bruin, Robert Entjes, Diederik Gommers, Dharmanand Ramnarain, Marlijn J A Kamps, Mark Hoogendoorn, Evelien A. N. Oostdijk, Martijn G. Scholtemeijer, Age D Boelens, Armand R. J. Girbes, Fleur G C A Nooteboom, Barbara Festen-Spanjer, Peter Koetsier, Giovanni Cinà, Hidde Hovenkamp, Sefanja Achterberg, Ellen G M Smit, Robbert C. A. Lalisang, D Jannet Mehagnoul-Schipper, Rob J. Bosman, Patrick Thoral, Judith Lens, Tariq A Dam, Olaf L. Cremer, Lucas M. Fleuren, Martijn Beudel, Paul W. G. Elbers, Tom Dormans, Aletta A. de Beer, Marco Peters, Alexander D. Cornet, Tim Frenzel, Louise C Urlings-Strop, Michele Tonutti, Mattia Fornasa, Walter van den Tempel, Davide Quintarelli, A Karakus, Stefaan H A Hendriks, Artificial intelligence, Network Institute, Computational Intelligence, Intensive Care, Intensive care medicine, ACS - Diabetes & metabolism, AII - Infectious diseases, ACS - Microcirculation, APH - Quality of Care, Intensive Care Medicine, AII - Inflammatory diseases, Neurology, and ANS - Neurodegeneration
Subjects: Critical Care, Critical Illness, Big data, Data validation, Critical Care and Intensive Care Medicine, computer.software_genre, Database, SDG 3 - Good Health and Well-being, Data Warehousing, Intensive care, Electronic Health Records, Humans, Medicine, Netherlands, RC86-88.9, business.industry, Research, Other Research Radboud Institute for Health Sciences [Radboudumc 0], COVID-19, Medical emergencies. Critical care. Intensive care. First aid, Missing data, Data warehouse, Hospitalization, Data sharing, Intensive Care Units, Life support, Pseudonymized, business, computer
Abstract: Background The Coronavirus disease 2019 (COVID-19) pandemic has underlined the urgent need for reliable, multicenter, and full-admission intensive care data to advance our understanding of the course of the disease and investigate potential treatment strategies. In this study, we present the Dutch Data Warehouse (DDW), the first multicenter electronic health record (EHR) database with full-admission data from critically ill COVID-19 patients. Methods A nation-wide data sharing collaboration was launched at the beginning of the pandemic in March 2020. All hospitals in the Netherlands were asked to participate and share pseudonymized EHR data from adult critically ill COVID-19 patients. Data included patient demographics, clinical observations, administered medication, laboratory determinations, and data from vital sign monitors and life support devices. Data sharing agreements were signed with participating hospitals before any data transfers took place. Data were extracted from the local EHRs with prespecified queries and combined into a staging dataset through an extract–transform–load (ETL) pipeline. In the consecutive processing pipeline, data were mapped to a common concept vocabulary and enriched with derived concepts. Data validation was a continuous process throughout the project. All participating hospitals have access to the DDW. Within legal and ethical boundaries, data are available to clinicians and researchers. Results Out of the 81 intensive care units in the Netherlands, 66 participated in the collaboration, 47 have signed the data sharing agreement, and 35 have shared their data. Data from 25 hospitals have passed through the ETL and processing pipeline. Currently, 3464 patients are included in the DDW, both from wave 1 and wave 2 in the Netherlands. More than 200 million clinical data points are available. Overall ICU mortality was 24.4%. Respiratory and hemodynamic parameters were most frequently measured throughout a patient's stay. For each patient, all administered medication and their daily fluid balance were available. Missing data are reported for each descriptive. Conclusions In this study, we show that EHR data from critically ill COVID-19 patients may be lawfully collected and can be combined into a data warehouse. These initiatives are indispensable to advance medical data science in the field of intensive care medicine.
Published: 2021

48. Pre-admission anticoagulant therapy and mortality in hospitalized COVID-19 patients: A retrospective cohort study

Author: Auke C Reidinga, Suat Simsek, Frits H.M. van Osch, Harry R. Büller, Nicole P. Juffermans, Saskia Middeldorp, Niels Gritters, Didier Collard, Matthijs Oudkerk, Marjolein A Heuvelmans, Hugo ten Cate, Renée A. Douma, Eline A Vlot, Thijs F. van Haaps, Nick van Es, Alexander P.J. Vlaar, Arno Maas, Marije ten Wolde, Michiel Coppens, Martijn Beudel, Martijn D. de Kruif, Joop P. W. van den Bergh, Graduate School, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, Amsterdam Reproduction & Development (AR&D), Intensive Care Medicine, ACS - Microcirculation, Neurology, Amsterdam Neuroscience - Neurodegeneration, ACS - Atherosclerosis & ischemic syndromes, Epidemiologie, RS: NUTRIM - R3 - Respiratory & Age-related Health, Interne Geneeskunde, MUMC+: HVC Pieken Trombose (9), MUMC+: MA Alg Interne Geneeskunde (9), MUMC+: HVC Trombosezorg (8), and RS: Carim - B04 Clinical thrombosis and Haemostasis
Subjects: 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Letter to the Editors-in-Chief, COVID-19, Anticoagulants, Retrospective cohort study, Thrombosis, Hematology, medicine.disease, Anticoagulant therapy, Internal medicine, medicine, Humans, Original Article, Hospital Mortality, Mortality, business, Retrospective Studies
Abstract: Background Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19. Methods In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support–free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of −1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. Results The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support–free days was 1 (interquartile range, −1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, −1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio
Published: 2021

49. General Anesthesia vs Local Anesthesia in Microelectrode Recording–Guided Deep-Brain Stimulation for Parkinson Disease: The GALAXY Randomized Clinical Trial

Author: Joke M. Dijk, Pepijn van den Munckhof, Rozemarije A. Holewijn, Vincent J. J. Odekerken, Martijn Beudel, Maarten Bot, Gert J. Geurtsen, Dagmar Verbaan, Rob M.A. de Bie, P. Rick Schuurman, Graduate School, Neurosurgery, ANS - Neurodegeneration, ANS - Neurovascular Disorders, ANS - Systems & Network Neuroscience, Neurology, APH - Mental Health, and APH - Aging & Later Life
Subjects: Male, Movement disorders, Deep brain stimulation, medicine.medical_treatment, Deep Brain Stimulation, Anesthesia, General, behavioral disciplines and activities, law.invention, Randomized controlled trial, Rating scale, law, Subthalamic Nucleus, medicine, Humans, Local anesthesia, Original Investigation, Aged, business.industry, Parkinson Disease, Middle Aged, nervous system diseases, Clinical trial, Subthalamic nucleus, Mood, Treatment Outcome, Anesthesia, Female, Neurology (clinical), medicine.symptom, business, Microelectrodes, Anesthesia, Local
Abstract: Importance It is unknown if there is a difference in outcome in asleep vs awake deep brain stimulation (DBS) of the subthalamic nucleus for advanced Parkinson disease. Objective To determine the difference in adverse effects concerning cognition, mood, and behavior between awake and asleep DBS favoring the asleep arm of the study. Design, setting, and participants This study was a single-center prospective randomized open-label blinded end point clinical trial. A total of 187 persons with Parkinson disease were referred for DBS between May 2015 to March 2019. Analysis took place from January 2016 to January 2020. The primary outcome follow-up visit was conducted 6 months after DBS. Interventions Bilateral subthalamic nucleus DBS was performed while the patient was asleep (under general anesthesia) in 1 study arm and awake in the other study arm. Both arms of the study used a frame-based intraoperative microelectrode recording technique to refine final target placement of the DBS lead. Main outcomes and measures The primary outcome variable was the between-group difference in cognitive, mood, and behavioral adverse effects as measured by a composite score. The secondary outcomes included the Movement Disorders Society Unified Parkinson's Disease Rating Scale, the patient assessment of surgical burden and operative time. Results A total of 110 patients were randomized to awake (local anesthesia; n = 56; mean [SD] age, 60.0 (7.4) years; 40 [71%] male) or to asleep (general anesthesia; n = 54; mean [SD] age, 61.3 [7.9] years; 38 [70%] male) DBS surgery. The 6-month follow-up visit was completed by 103 participants. The proportion of patients with adverse cognitive, mood, and behavioral effects on the composite score was 15 of 52 (29%) after awake and 11 of 51 (22%) after asleep DBS (odds ratio, 0.7 [95% CI, 0.3-1.7]). There was no difference in improvement in the off-medication Movement Disorders Society Unified Parkinson's Disease Rating Scale Motor Examination scores between groups (awake group: mean [SD], -27.3 [17.5] points; asleep group: mean [SD], -25.3 [14.3] points; mean difference, -2.0 [95% CI, -8.1 to 4.2]). Asleep surgery was experienced as less burdensome by patients and was 26 minutes shorter than awake surgery. Conclusions and relevance There was no difference in the primary outcome of asleep vs awake DBS. Future large randomized clinical trials should examine some of the newer asleep based DBS technologies because this study was limited to frame-based microelectrode-guided procedures. Trial registration trialregister.nl Identifier: NTR5809.
Published: 2021

50. Predicting mortality of individual patients with COVID-19: A multicentre Dutch cohort

Author: Marcel J. H. Aries, Auke C Reidinga, Lucas A. Ramos, Kim C. E. Sigaloff, Wouter V. Potters, Suat Simsek, Iwan C. C. van der Horst, Peter G. Noordzij, Tom Dormans, Caroline E. Wyers, Henk A. Marquering, Maarten C. Ottenhoff, Ella H C van den Hout, Michiel Schinkel, Dan Piña-Fuentes, Guido van Wingen, Deborah Hubers, Lianne de Haan, Roger J M W Rennenberg, Rajat M. Thomas, Daisy Rusch, W. Joost Wiersinga, Christian Herff, Marcus L.F. Janssen, Shi Hu, Renée A. Douma, Niels C. Gritters van den Oever, Egill Axfjord Fridgeirsson, Martijn D. de Kruif, Max Welling, Joop P. W. van den Bergh, Martijn Beudel, Paul W. G. Elbers, Pieter L. Kubben, Lucas M Fleuren, David T B Buis, RS: MHeNs - R3 - Neuroscience, Neurochirurgie, MUMC+: HZC Med Staf Spec Klinische Neurofys (9), Klinische Neurowetenschappen, Intensive Care, MUMC+: MA Intensive Care (3), MUMC+: MA Medische Staf IC (9), RS: Carim - V04 Surgical intervention, MUMC+: MA Med Staf Spec Neurochirurgie (9), Interne Geneeskunde, MUMC+: MA Alg Interne Geneeskunde (9), RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Neurology, Amsterdam Neuroscience - Systems & Network Neuroscience, Intensive care medicine, Internal medicine, APH - Quality of Care, ACS - Diabetes & metabolism, Amsterdam Machine Learning lab (IVI, FNWI), IvI Research (FNWI), Video & Image Sense Lab (IvI, FNWI), Biomedical Engineering and Physics, Adult Psychiatry, ACS - Atherosclerosis & ischemic syndromes, APH - Methodology, ANS - Brain Imaging, ANS - Cellular & Molecular Mechanisms, ANS - Compulsivity, Impulsivity & Attention, ANS - Neurovascular Disorders, AMS - Amsterdam Movement Sciences, Graduate School, Radiology and Nuclear Medicine, Center of Experimental and Molecular Medicine, Infectious diseases, AII - Infectious diseases, APH - Mental Health, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, and ANS - Neurodegeneration
Subjects: medicine.medical_specialty, Palliative care, medicine.medical_treatment, Health Informatics, 030204 cardiovascular system & hematology, Logistic regression, risk management, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Oxygen therapy, medicine, Humans, 030212 general & internal medicine, Retrospective Studies, Oxygen saturation (medicine), Receiver operating characteristic, SARS-CoV-2, business.industry, public health, COVID-19, Retrospective cohort study, General Medicine, Logistic Models, Cohort, Medicine, business, Cohort study
Abstract: ObjectiveDevelop and validate models that predict mortality of patients diagnosed with COVID-19 admitted to the hospital.DesignRetrospective cohort study.SettingA multicentre cohort across 10 Dutch hospitals including patients from 27 February to 8 June 2020.ParticipantsSARS-CoV-2 positive patients (age ≥18) admitted to the hospital.Main outcome measures21-day all-cause mortality evaluated by the area under the receiver operator curve (AUC), sensitivity, specificity, positive predictive value and negative predictive value. The predictive value of age was explored by comparison with age-based rules used in practice and by excluding age from the analysis.Results2273 patients were included, of whom 516 had died or discharged to palliative care within 21 days after admission. Five feature sets, including premorbid, clinical presentation and laboratory and radiology values, were derived from 80 features. Additionally, an Analysis of Variance (ANOVA)-based data-driven feature selection selected the 10 features with the highest F values: age, number of home medications, urea nitrogen, lactate dehydrogenase, albumin, oxygen saturation (%), oxygen saturation is measured on room air, oxygen saturation is measured on oxygen therapy, blood gas pH and history of chronic cardiac disease. A linear logistic regression and non-linear tree-based gradient boosting algorithm fitted the data with an AUC of 0.81 (95% CI 0.77 to 0.85) and 0.82 (0.79 to 0.85), respectively, using the 10 selected features. Both models outperformed age-based decision rules used in practice (AUC of 0.69, 0.65 to 0.74 for age >70). Furthermore, performance remained stable when excluding age as predictor (AUC of 0.78, 0.75 to 0.81).ConclusionBoth models showed good performance and had better test characteristics than age-based decision rules, using 10 admission features readily available in Dutch hospitals. The models hold promise to aid decision-making during a hospital bed shortage.
Published: 2021

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