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1. Postoperative 30-day complications after cemented/hybrid versus cementless total hip arthroplasty in osteoarthritis patients > 70 years: A multicenter study from the Lundbeck Foundation Centre for Fast-track Hip and Knee replacement database and the Danish Hip Arthroplasty Register

Author

Martin Lindberg-Larsen, Pelle Baggesgaard Petersen, Christoffer Calov Jørgensen, Søren Overgaard, Henrik Kehlet, and Lundbeck Foundation Center for Fast-track Hip and Knee Arthroplasty Collaborating Group

Subjects
Orthopedic surgery, RD701-811
Abstract

Background and purpose — The use of cementless total hip arthroplasty (THA) in elderly patients is debated because of increased risk of early periprosthetic femoral fractures. However, cemented femoral components carry a risk of bone cement implantation syndrome. Hence, we compared in-hospital complications, complications leading to readmission and mortality ≤ 30 days postoperatively between hybrid/cemented (cemented femoral component) vs. cementless THA in osteoarthritis patients > 70 years. Patients and methods — This is a prospective observational cohort study in 9 centers from January 2010 to August 2017. We used 30-day follow-up from the Danish National Patient Registry, patient records, and data from the Danish Hip Arthroplasty Register. Only THAs performed as a result of osteoarthritis were included. Results — 3,368 (42%) of the THAs were cemented/hybrid and 4,728 (58%) cementless. The in-hospital complication risk was 7.7% after cemented/hybrid vs. 5.3% after cementless THA (< 0.001), statistically not significant when adjusting for comorbidities (p = 0.1). There were similar risks of complications causing readmission (5.7% vs. 6.2%) and mortality ≤ 30 days (0.2% vs. 0.3%). 15 cases (0.4%) of pulmonary embolism (PE) were found after cemented/hybrid vs. 4 (0.1%) after cementless THA (p = 0.001); none occurred within 24 hours postoperatively. 2 of the PEs after cementless THA led to mortality. Cemented/hybrid THA remained significantly associated with risk of PE (RR 3.9, p = 0.02), when adjusting for comorbidities. BMI > 35 was associated with highest risk of PE (RR 5.7, p = 0.003). The risk of periprosthetic femoral fracture was 0.2% after cemented/hybrid vs. 1.5% after cementless THA (p < 0.001) and the risk of dislocations was 1.2% after cemented/hybrid THA vs. 1.8% after cementless THA (p = 0.04). Interpretation — The higher risk of PE after cemented/hybrid THA and higher risk of periprosthetic femoral fractures and dislocations after cementless THA highlights that both medically and surgically complications are related to fixation technique and have to be considered.

Published
2020
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15. Precision Medicine in the Depression Treatment (BDD)

Author

Mental Health Services in the Capital Region, Denmark, Center for Integrated Molecular Brain Imaging, Copenhagen, Denmak, Lundbeck Foundation, and Gitte Moos Knudsen, MD,Professor

Published
2022

19. Danish Rct on Exercise Versus Arthroscopic Meniscal Surgery for Young Adults (DREAM)

Author

Aarhus University Hospital, Copenhagen University Hospital, Hvidovre, Aalborg University Hospital, Sygehus Lillebaelt, Naestved Hospital, Odense University Hospital, Slagelse Hospital, Danish Council for Independent Research, IMK Almene Fond, Lundbeck Foundation, The Danish Rheumatism Association, Spar Nord Foundation, Association of Danish Physiotherapists, Regionshospitalet Silkeborg, and Søren Thorgaard Skou, PT, PhD, Professor

Published
2022

20. A polygenic resilience score moderates the genetic risk for schizophrenia.

Author

Hess, Jonathan L, Tylee, Daniel S, Mattheisen, Manuel, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Børglum, Anders D, Als, Thomas D, Grove, Jakob, Werge, Thomas, Mortensen, Preben Bo, Mors, Ole, Nordentoft, Merete, Hougaard, David M, Byberg-Grauholm, Jonas, Bækvad-Hansen, Marie, Greenwood, Tiffany A, Tsuang, Ming T, Curtis, David, Steinberg, Stacy, Sigurdsson, Engilbert, Stefánsson, Hreinn, Stefánsson, Kári, Edenberg, Howard J, Holmans, Peter, Faraone, Stephen V, and Glatt, Stephen J

Subjects
Schizophrenia Working Group of the Psychiatric Genomics Consortium, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Humans, Genetic Predisposition to Disease, Risk Factors, Schizophrenia, Genomics, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Alleles, Genome-Wide Association Study, Human Genome, Genetics, Brain Disorders, Mental Health, Prevention, Serious Mental Illness, 2.1 Biological and endogenous factors, Mental health, Psychiatry, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences
Abstract

Based on the discovery by the Resilience Project (Chen R. et al. Nat Biotechnol 34:531-538, 2016) of rare variants that confer resistance to Mendelian disease, and protective alleles for some complex diseases, we posited the existence of genetic variants that promote resilience to highly heritable polygenic disorders1,0 such as schizophrenia. Resilience has been traditionally viewed as a psychological construct, although our use of the term resilience refers to a different construct that directly relates to the Resilience Project, namely: heritable variation that promotes resistance to disease by reducing the penetrance of risk loci, wherein resilience and risk loci operate orthogonal to one another. In this study, we established a procedure to identify unaffected individuals with relatively high polygenic risk for schizophrenia, and contrasted them with risk-matched schizophrenia cases to generate the first known "polygenic resilience score" that represents the additive contributions to SZ resistance by variants that are distinct from risk loci. The resilience score was derived from data compiled by the Psychiatric Genomics Consortium, and replicated in three independent samples. This work establishes a generalizable framework for finding resilience variants for any complex, heritable disorder.

Published
2021

22. Gastrointestinal Motility Among Diabetes Patients

Author

Novo Nordisk A/S, Svend Faelding Humanitarian Foundation, Copenhagen University Foundation for Medical Students, Hoejmosegaard Foundation, Holger Rabitz og Hustru Doris Mary foedt Phillipps Mindelegat, Lundbeck Foundation, Wilhelm Frank og Angelina Franks Mindelegat, Torben og Alice Frimodts Fond, and Fonden til Lægevidenskabens Fremme, A.P. Møller Fonden

Published
2021

27. Population genomics of post-glacial western Eurasia

Author

Lundbeck Foundation, Novo Nordisk Foundation, Wellcome Trust, Carlsberg Foundation, Danish National Research Foundation, University of Copenhagen, Ferring Pharmaceuticals, Swedish Foundation for Humanities and Social Sciences, Villum Fonden, Independent Research Fund Denmark, Hanne and Torkel Weis-Fogh Fund, Wellcome, Swiss National Science Foundation, European Research Council, Aarhus University Research Foundation, Ministry of Education and Science (Kazakhstan), Ministerio de Economía y Competitividad (España), Ministero dell'Istruzione, dell'Università e della Ricerca, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Generalitat Valenciana, Nomis Foundation, European Commission, Ministry of Science and Higher Education of the Russian Federation, Ministry of Education, Science, Culture and Sports of the Republic of Armenia, National Institute of General Medical Sciences (US), Sikora, Martin [0000-0003-2818-8319], Lalueza-Fox, Carles [0000-0002-1730-5914], Allentoft, Morten, Sikora, Martin, Refoyo-Martínez, Alba, Irving-Pease, Evan K., Fischer, Anders, Barrie, William, Ingason, Andrés, Stenderup, Jesper, Sjögren, Karl-Göran, Pearson, Alice, Mota, Bárbara Sousa da, Schulz Paulsson, Bettina, Halgren, Alma, Macleod, Ruairidh, Jørkov, Marie Louise S., Demeter, Fabrice, Sørensen, Lasse, Nielsen, Poul Otto, Henriksen, Rasmus A., Vimala, Tharsika, McColl, Hugh, Margaryan, Ashot, Ilardo, Melissa, Vaughn, Andrew, Fischer Mortensen, Morten, Nielsen, Anne Birgitte, Ulfeldt Hede, Mikkel, Johannsen, Niels Nørkjær, Rasmussen, Peter, Vinner, Lasse, Renaud, Gabriel, Stern, Aaron, Trolle Jensen, Theis Zetner, Scorrano, Gabriele, Schroeder, Hannes, Lysdahl, Per, Ramsøe, Abigail Daisy, Skorobogatov, Andrei, Schork, Andrew Joseph, Rosengren, Anders, Ruter, Anthony, Outram, Alan, Timoshenko, Aleksey A., Buzhilova, Alexandra, Coppa, Alfredo, Zubova, Alisa, Silva, Ana María, Hansen, Anders J., Gromov, Andrey, Logvin, Andrey, Gotfredsen, Anne Birgitte, Nielsen, Bjarne Henning, González-Rabanal, Borja, Lalueza-Fox, Carles, McKenzie, Catriona J., Gaunitz, Charleen, Blasco, Concepción, Liesau, Corina, Martínez-Labarga, Cristina, Pozdnyakov, Dmitri V., Cuenca-Solana, David, Lordkipanidze, David O., En’shin, Dmitri, Salazar García, Domingo Carlos, Price, T. Douglas, Borić, Dušan, Kostyleva, Elena, Veselovskaya, Elizaveta V., Usmanova, Emma R., Cappellini, Enrico, Petersen, Erik Brinch, Kannegaard, Esben, Radina, Francesca, Yediay, Fulya Eylem, Duday, Henri, Gutiérrez-Zugasti, Igor, Merts, Ilya, Potekhina, Inna, Shevnina, Irina, Altinkaya, Isin, Guilaine, Jean, Hansen, Jesper, Aura Tortosa, Joan Emili, Zilhão, João, Vega, Jorge, Pedersen, Kristoffer Buck, Tunia, Krzysztof, Zhao, Lei, Mylnikova, Liudmila N., Larsson, Lars, Metz, Laure, Yepiskoposyan, Levon, Pedersen, Lisbeth, Sarti, Lucia, Orlando, Ludovic, Slimak, Ludovic, Klassen, Lutz, Blank, Malou, González-Morales, Manuel, Silvestrini, Mara, Vretemark, Maria, Nesterova, Marina S., Rykun, Marina, Rolfo, Mario Federico, Szmyt, Marzena, Przybyła, Marcin, Calattini, Mauro, Sablin, Mikhail, Dobisíková, Miluše, Meldgaard, Morten, Johansen, Morten, Berezina, Natalia, Card, Nick, Saveliev, Nikolai A., Poshekhonova, Olga, Rickards, Olga, Lozovskaya, Olga V., Gábor, Olivér, Uldum, Otto Christian, Aurino, Paola, Kosintsev, Pavel, Courtaud, Patrice, Ríos, Patricia, Mortensen, Peder, Lotz, Per, Persson, Per, Bangsgaard, Pernille, Barros Damgaard, Peter de, Petersen, Peter Vang, Prieto Martínez, Pilar, Włodarczak, Piotr, Smolyaninov, Roman V., Maring, Rikke, Menduiña, Roberto, Badalyan, Ruben, Iversen, Rune, Turin, Ruslan, Vasilyev, Sergey, Wåhlin, Sidsel, Borutskaya, Svetlana, Skochina, Svetlana, Sørensen, Søren Anker, Andersen, Søren H., Jørgensen, Thomas, Serikov, Yuri B., Molodin, Vyacheslav I., Smrcka, Vaclav, Merts, Victor, Appadurai, Vivek, Moiseyev, Vyacheslav, Magnusson, Yvonne, Kjær, Kurt H., Lynnerup, Niels, Lawson, Daniel J., Sudmant, Peter H., Rasmussen, Simon, Korneliussen, Thorfinn Sand, Durbin, Richard, Nielsen, Rasmus, Delaneau, Olivier, Werge, Thomas, Racimo, Fernando, Kristiansen, Kristian, Willerslev, Eske, Lundbeck Foundation, Novo Nordisk Foundation, Wellcome Trust, Carlsberg Foundation, Danish National Research Foundation, University of Copenhagen, Ferring Pharmaceuticals, Swedish Foundation for Humanities and Social Sciences, Villum Fonden, Independent Research Fund Denmark, Hanne and Torkel Weis-Fogh Fund, Wellcome, Swiss National Science Foundation, European Research Council, Aarhus University Research Foundation, Ministry of Education and Science (Kazakhstan), Ministerio de Economía y Competitividad (España), Ministero dell'Istruzione, dell'Università e della Ricerca, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Generalitat Valenciana, Nomis Foundation, European Commission, Ministry of Science and Higher Education of the Russian Federation, Ministry of Education, Science, Culture and Sports of the Republic of Armenia, National Institute of General Medical Sciences (US), Sikora, Martin [0000-0003-2818-8319], Lalueza-Fox, Carles [0000-0002-1730-5914], Allentoft, Morten, Sikora, Martin, Refoyo-Martínez, Alba, Irving-Pease, Evan K., Fischer, Anders, Barrie, William, Ingason, Andrés, Stenderup, Jesper, Sjögren, Karl-Göran, Pearson, Alice, Mota, Bárbara Sousa da, Schulz Paulsson, Bettina, Halgren, Alma, Macleod, Ruairidh, Jørkov, Marie Louise S., Demeter, Fabrice, Sørensen, Lasse, Nielsen, Poul Otto, Henriksen, Rasmus A., Vimala, Tharsika, McColl, Hugh, Margaryan, Ashot, Ilardo, Melissa, Vaughn, Andrew, Fischer Mortensen, Morten, Nielsen, Anne Birgitte, Ulfeldt Hede, Mikkel, Johannsen, Niels Nørkjær, Rasmussen, Peter, Vinner, Lasse, Renaud, Gabriel, Stern, Aaron, Trolle Jensen, Theis Zetner, Scorrano, Gabriele, Schroeder, Hannes, Lysdahl, Per, Ramsøe, Abigail Daisy, Skorobogatov, Andrei, Schork, Andrew Joseph, Rosengren, Anders, Ruter, Anthony, Outram, Alan, Timoshenko, Aleksey A., Buzhilova, Alexandra, Coppa, Alfredo, Zubova, Alisa, Silva, Ana María, Hansen, Anders J., Gromov, Andrey, Logvin, Andrey, Gotfredsen, Anne Birgitte, Nielsen, Bjarne Henning, González-Rabanal, Borja, Lalueza-Fox, Carles, McKenzie, Catriona J., Gaunitz, Charleen, Blasco, Concepción, Liesau, Corina, Martínez-Labarga, Cristina, Pozdnyakov, Dmitri V., Cuenca-Solana, David, Lordkipanidze, David O., En’shin, Dmitri, Salazar García, Domingo Carlos, Price, T. Douglas, Borić, Dušan, Kostyleva, Elena, Veselovskaya, Elizaveta V., Usmanova, Emma R., Cappellini, Enrico, Petersen, Erik Brinch, Kannegaard, Esben, Radina, Francesca, Yediay, Fulya Eylem, Duday, Henri, Gutiérrez-Zugasti, Igor, Merts, Ilya, Potekhina, Inna, Shevnina, Irina, Altinkaya, Isin, Guilaine, Jean, Hansen, Jesper, Aura Tortosa, Joan Emili, Zilhão, João, Vega, Jorge, Pedersen, Kristoffer Buck, Tunia, Krzysztof, Zhao, Lei, Mylnikova, Liudmila N., Larsson, Lars, Metz, Laure, Yepiskoposyan, Levon, Pedersen, Lisbeth, Sarti, Lucia, Orlando, Ludovic, Slimak, Ludovic, Klassen, Lutz, Blank, Malou, González-Morales, Manuel, Silvestrini, Mara, Vretemark, Maria, Nesterova, Marina S., Rykun, Marina, Rolfo, Mario Federico, Szmyt, Marzena, Przybyła, Marcin, Calattini, Mauro, Sablin, Mikhail, Dobisíková, Miluše, Meldgaard, Morten, Johansen, Morten, Berezina, Natalia, Card, Nick, Saveliev, Nikolai A., Poshekhonova, Olga, Rickards, Olga, Lozovskaya, Olga V., Gábor, Olivér, Uldum, Otto Christian, Aurino, Paola, Kosintsev, Pavel, Courtaud, Patrice, Ríos, Patricia, Mortensen, Peder, Lotz, Per, Persson, Per, Bangsgaard, Pernille, Barros Damgaard, Peter de, Petersen, Peter Vang, Prieto Martínez, Pilar, Włodarczak, Piotr, Smolyaninov, Roman V., Maring, Rikke, Menduiña, Roberto, Badalyan, Ruben, Iversen, Rune, Turin, Ruslan, Vasilyev, Sergey, Wåhlin, Sidsel, Borutskaya, Svetlana, Skochina, Svetlana, Sørensen, Søren Anker, Andersen, Søren H., Jørgensen, Thomas, Serikov, Yuri B., Molodin, Vyacheslav I., Smrcka, Vaclav, Merts, Victor, Appadurai, Vivek, Moiseyev, Vyacheslav, Magnusson, Yvonne, Kjær, Kurt H., Lynnerup, Niels, Lawson, Daniel J., Sudmant, Peter H., Rasmussen, Simon, Korneliussen, Thorfinn Sand, Durbin, Richard, Nielsen, Rasmus, Delaneau, Olivier, Werge, Thomas, Racimo, Fernando, Kristiansen, Kristian, and Willerslev, Eske

Abstract

Western Eurasia witnessed several large-scale human migrations during the Holocene1,2,3,4,5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 BP, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 BP, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.

Published
2024

28. Impaired cholinergic integrity of the colon and pancreas in dementia with Lewy bodies

Author

Instituto de Salud Carlos III, European Commission, Aase og Ejnar Danielsens Fond, Michael J. Fox Foundation for Parkinson's Research, Lundbeck Foundation, Grothe, Michel J. [0000-0003-2600-9022], Okkels, Niels, Horsager, Jacob, Fedorova, Tatyana D., Knudsen, Karoline, Skjærbæk, Casper, Andersen, Katrine B., Labrador-Espinosa, Miguel, Vestergård, Karsten, Mortensen, Janne, Klit, Henriette, Møller, Mette, Danielsen, Erik H., Johnsen, Erik L., Bekan, Goran, Hansen, Kim V., Munk, Ole L., Damholdt, Malene F., Kjeldsen, Pernille L., Hansen, Allan K., Gottrup, Hanne, Grothe, Michel J., Borghammer, Per, Instituto de Salud Carlos III, European Commission, Aase og Ejnar Danielsens Fond, Michael J. Fox Foundation for Parkinson's Research, Lundbeck Foundation, Grothe, Michel J. [0000-0003-2600-9022], Okkels, Niels, Horsager, Jacob, Fedorova, Tatyana D., Knudsen, Karoline, Skjærbæk, Casper, Andersen, Katrine B., Labrador-Espinosa, Miguel, Vestergård, Karsten, Mortensen, Janne, Klit, Henriette, Møller, Mette, Danielsen, Erik H., Johnsen, Erik L., Bekan, Goran, Hansen, Kim V., Munk, Ole L., Damholdt, Malene F., Kjeldsen, Pernille L., Hansen, Allan K., Gottrup, Hanne, Grothe, Michel J., and Borghammer, Per

Abstract

Dementia with Lewy bodies is characterized by a high burden of autonomic dysfunction and Lewy pathology in peripheral organs and components of the sympathetic and parasympathetic nervous system. Parasympathetic terminals may be quantified with 18F-fluoroetoxybenzovesamicol, a PET tracer that binds to the vesicular acetylcholine transporter in cholinergic presynaptic terminals. Parasympathetic imaging may be useful for diagnostics, improving our understanding of autonomic dysfunction and for clarifying the spatiotemporal relationship of neuronal degeneration in prodromal disease. Therefore, we aimed to investigate the cholinergic parasympathetic integrity in peripheral organs and central autonomic regions of subjects with dementia with Lewy bodies and its association with subjective and objective measures of autonomic dysfunction. We hypothesized that organs with known parasympathetic innervation, especially the pancreas and colon, would have impaired cholinergic integrity. To achieve these aims, we conducted a cross-sectional comparison study including 23 newly diagnosed non-diabetic subjects with dementia with Lewy bodies (74 ± 6 years, 83% male) and 21 elderly control subjects (74 ± 6 years, 67% male). We obtained whole-body images to quantify PET uptake in peripheral organs and brain images to quantify PET uptake in regions of the brainstem and hypothalamus. Autonomic dysfunction was assessed with questionnaires and measurements of orthostatic blood pressure. Subjects with dementia with Lewy bodies displayed reduced cholinergic tracer uptake in the pancreas (32% reduction, P = 0.0003) and colon (19% reduction, P = 0.0048), but not in organs with little or no parasympathetic innervation. Tracer uptake in a region of the medulla oblongata overlapping the dorsal motor nucleus of the vagus correlated with autonomic symptoms (rs = −0.54, P = 0.0077) and changes in orthostatic blood pressure (rs = 0.76, P < 0.0001). Tracer uptake in the pedunculopontine region correlat

Published
2024

41. Intermediate Care - Effect on Mortality Following Emergency Abdominal Surgery (InCare)

Author

University of Copenhagen, Copenhagen Trial Unit, Center for Clinical Intervention Research, Herlev Hospital, Sygekassernes Helsefond, Danish Council for Independent Research, AP Moeller Foundation, Lundbeck Foundation, Hilleroed Hospital, Zealand University Hospital, Bispebjerg Hospital, Herning Hospital, Aabenraa Hospital, Vejle Hospital, and Morten Vester-Andersen, MD, Senior resident

Published
2015

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