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1. Infectious complications in children with malignant bone tumors: a multicenter nationwide study

Author

Czyzewski K, Galazka P, Zalas-Wiecek P, Gryniewicz-Kwiatkowska O, Gietka A, Semczuk K, Chelmecka-Wiktorczyk L, Zak I, Salamonowicz M, Fraczkiewicz J, Zajac-Spychala O, Bien E, Plonowski M, Wawrykow P, Pierlejewski F, Gamrot Z, Malas Z, Stolpa W, Musial J, and Styczynski J

Subjects
infectious complications, risk factors analysis, Ewing sarcoma, osteosarcoma, malignant bone tumor, children, Infectious and parasitic diseases, RC109-216
Abstract

Krzysztof Czyzewski,1 Przemyslaw Galazka,2 Patrycja Zalas-Wiecek,3 Olga Gryniewicz-Kwiatkowska,4 Agnieszka Gietka,4 Katarzyna Semczuk,5 Liliana Chelmecka-Wiktorczyk,6 Iwona Zak,7 Malgorzata Salamonowicz,8 Jowita Fraczkiewicz,8 Olga Zajac-Spychala,9 Ewa Bien,10 Marcin Plonowski,11 Pawel Wawrykow,12 Filip Pierlejewski,13 Zuzanna Gamrot,14 Zofia Malas,15 Weronika Stolpa,16 Jakub Musial,17 Jan Styczynski11Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University Torun, Bydgoszcz, Poland; 2Department of General and Oncological Surgery for Children and Adolescents, Collegium Medicum, Nicolaus Copernicus University Torun, Bydgoszcz, Poland; 3Department of Microbiology, Collegium Medicum, Nicolaus Copernicus University Torun, Bydgoszcz, Poland; 4Department of Oncology, Children’s Memorial Health Institute, Warsaw, Poland; 5Department of Microbiology, Children’s Memorial Health Institute, Warsaw, Poland; 6Department of Pediatric Oncology and Hematology, University Children’s Hospital, Jagiellonian University, Collegium Medicum, Krakow, Poland; 7Department of Microbiology, University Children’s Hospital, Jagiellonian University, Collegium Medicum, Krakow, Poland; 8Department of Pediatric Stem Cell Transplantation, Hematology and Oncology, Medical University, Wroclaw, Poland; 9Department of Pediatric Oncology, Hematology and Transplantology, University of Medical Sciences, Poznan, Poland; 10Department of Pediatrics, Hematology and Oncology, Medical University, Gdansk, Poland; 11Department of Pediatric Oncology and Hematology, Medical University, Bialystok, Poland; 12Department of Pediatrics and Pediatric Oncology, Pomeranian Medical University, Szczecin, Poland; 13Department of Pediatric Oncology and Hematology, Medical University, Lodz, Poland; 14Division of Pediatric Hematology and Oncology, Chorzow City Hospital, Chorzow, Poland; 15Division of Pediatric Hematology and Oncology, Children Hospital, Olsztyn, Poland; 16Division of Pediatric Oncology, Hematology and Chemotherapy, Department of Pediatric, Silesian Medical University, Katowice, Poland; 17Department of Pediatric Oncohematology, Medical Faculty University of Rzeszow, Clinical Provincial Hospital No. 2, Rzeszow, PolandObjectives: The analysis of epidemiology, risk factors and outcome of infections in children with malignant bone tumors (MBT) undergoing chemotherapy.Methods: In this retrospective nationwide multicenter cross-sectional study, a total number of 126 children with MBT including 70 with Ewing sarcoma (ES) and 56 with osteosarcoma (OSA) were screened for infections over a period of 72 consecutive months.Results: The risk of infection was 7.15-fold higher in patients with ES as compared to the OSA group, especially concerning bacterial infections (4.1-fold increase risk). Bacterial infections occurred in 74.3% patients with ES and in 41.1% with OSA. The median time from diagnosis to first infection was 4.9 months. 33.0% of bacterial episodes were diagnosed as bloodstream (BSI), 31.1% as gastrointestinal tract, 30.1% as urinary tract infection. Infection-related mortality (IRM) from bacterial infection was 6% and 15% in ES and OSA patients, respectively. Cumulative incidence was 7.1% for invasive fungal disease and 6.3% for viral infections. The only significant risk factor for IRM was time to infection ≥5 months since the beginning of chemotherapy. All patients who have died from infection had BSI and were in neutropenia.Conclusions: Infections in the children with MBT in our study occurred with high frequency, especially in patients with ES. The most frequent were bacterial infections, while fungal and viral infections were episodic. Among the bacterial infections, bloodstream, urinary tract and gastrointestinal tract infections occurred with similar frequency. All deceased patients died due to BSI. Bacterial infection occurring ≥5 months since the beginning of chemotherapy was a risk factor for death.Keywords: infectious complications, risk factors analysis, Ewing sarcoma, osteosarcoma, malignant bone tumor, children

Published
2019

2. Evaluation of the efficacy and safety of three dosing regimens of agalsidase alfa enzyme replacement therapy in adults with Fabry disease

Author

Goláň L, Goker-Alpan O, Holida M, Kantola I, Klopotowski M, Kuusisto J, Linhart A, Musial J, Nicholls K, Gonzalez-Rodriguez D, Sharma R, Vujkovac B, Chang P, and Wijatyk A

Subjects
Therapeutics. Pharmacology, RM1-950
Abstract

Lubor Goláň,1 Ozlem Goker-Alpan,2 Myrl Holida,3 Ikka Kantola,4 Mariusz Klopotowski,5 Johanna Kuusisto,6 Aleš Linhart,1 Jacek Musial,7 Kathleen Nicholls,8 Derlis Gonzalez-Rodriguez,9 Reena Sharma,10 Bojan Vujkovac,11 Peter Chang,12 Anna Wijatyk12 1First Faculty of Medicine, Department of Cardiovascular Medicine, Charles University, Prague, Czech Republic; 2Lysosomal Research and Treatment Unit, Fairfax, VA, USA; 3Stead Family Department of Pediatrics, Division of Medical Genetics, University of Iowa Hospitals and Clinics, Iowa City, IA, USA; 4Division of Medicine, Turku University Hospital, Turku, Finland; 5Institute of Cardiology, Warsaw, Poland; 6Department of Medicine, Center for Medicine and Clinical Research, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland; 7Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland; 8Department of Nephrology, Royal Melbourne Hospital and the University of Melbourne, VIC, Australia; 9Instituto Privado de Hematologia E Investigacion Clinica (IPHIC), Asuncion, Paraguay; 10Salford Royal NHS Foundation Trust, Salford, UK; 11General Hospital Slovenj Gradec, Slovenj Gradec, Slovenia; 12Shire, Lexington, MA, USA Purpose: Efficacy and safety of agalsidase alfa at 0.2 mg/kg weekly were compared with 0.2 mg/kg every other week (EOW). Exploratory analyses were performed for 0.4 mg/kg weekly.Patients and methods: This was a 53-week, Phase III/IV, multicenter, open-label study (NCT01124643) in treatment-naïve adults (≥18 years) with Fabry disease. Inclusion criteria were left ventricular hypertrophy at baseline, defined as left ventricular mass indexed to height >50 g/m2.7 for males and >47 g/m2.7 for females. Primary endpoint was reduction of left ventricular mass indexed to height as assessed by echocardiography. Secondary endpoints included cardiac (peak oxygen consumption, 6-minute walk test, Minnesota Living with Heart Failure Questionnaire, New York Heart Association classification), renal (Modification of Diet in Renal Disease, estimated glomerular filtration rate), and biomarker (plasma globotriaosylceramide) assessments. Safety endpoints were adverse events and anti–agalsidase alfa antibodies.Results: Twenty patients were randomized to 0.2 mg/kg EOW (mean age, 50.3 years; 70% male), 19 to 0.2 mg/kg weekly (51.8 years; 53% male), and 5 to 0.4 mg/kg weekly (49.4 years; 40% male). The mean change in left ventricular mass indexed to height by Week 53 in the 0.2-mg/kg EOW and weekly groups was 3.2 g/m2.7 and 0.5 g/m2.7, with no significant difference between groups. No clinically meaningful changes by Week 53 were found within or between the 0.2-mg/kg groups for peak oxygen consumption, 6-minute walk test, or Minnesota Living with Heart Failure Questionnaire. Two patients in each group improved by ≥1 New York Heart Association classi­fication. No significant differences were found between 0.2 mg/kg EOW and weekly for mean change in estimated glomerular filtration rate (-1.21 mL/min/1.73 m2 vs -3.32 mL/min/1.73 m2) or plasma globotriaosylceramide (-1.05 nmol/mL vs -2.13 nmol/mL), respectively. Infusion-related adverse events were experienced by 25% and 21% in the 0.2-mg/kg EOW and weekly groups. Tachycardia, fatigue, and hypotension were experienced by two or more patients overall. Anti–agalsidase alfa antibodies were detected in 11.4% of patients and neutralizing antibodies in 6.8%. Infusion-related reactions did not appear to be correlated with antibody status.Conclusion: No efficacy or safety differences were found when the approved EOW dosage of agalsidase alfa was increased to weekly administration. Exploratory analyses for 0.4 mg/kg weekly showed similar results. Keywords: adverse events, exercise tolerance, left ventricular hypertrophy, lysosomal storage disorder, quality of life, renal function

Published
2015

4. Ultrafast dynamics and Raman imaging of metal complexes of tetrasulphonated phthalocyanines in human cancerous and noncancerous breast tissues

Author

Musial J., Freysz E., Tondusson M., Brozek-Pluska B., Jarota A., Abramczyk H., and Kordek R.

Subjects
Physics, QC1-999
Abstract

A promising material in medicine, electronics, optoelectronics, electrochemistry, catalysis and photophysics, Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) is investigated at biological interfaces of human breast tissue by means of time-resolved spectroscopy. The nature of fast processes and pathways of the competing relaxation mechanisms from the initially excited electronic states of a photosensitizer at biological interfaces have been studied. Comparison between the results in the biological environment of the breast tissues and in aqueous solutions demonstrates that the photochemical mechanisms become dramatically different. The presented results provide a basis for a substantial revision of the commonly accepted assumption that photochemistry of the bulk properties of photosensitizers in solutions can be translated to the interfacial region. First, in solution the dynamics of the photosensitizer is much slower than that at the biological interface. Second, the dynamics of the photosensitizer in the cancerous tissue is dramatically slower than that in noncancerous tissue. Our results provide evidence that molecular structures responsible for harvesting of the light energy in biological tissue find their ways for a recovery through some special features of the potential energy surfaces such as conical intersections, which facilitate the rate of radiationless transitions and maintain the photostability in the biological systems.

Published
2013
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5. Asthma similarities across ProAR (Brazil) and U-BIOPRED (Europe) adult cohorts of contrasting locations, ethnicity and socioeconomic status

Author

Alcantara-Neves, N., Almeida, P.C.A., Amorim, L., Araujo, M.I., Barnes, K.C., Barreto, M.L., Belitardo, E., Bião-Lima, V., Cardoso, L., Camargos, P.A., Chatkin, J.M., Costa, R.S., Coelho, A.C.C., Cooper, P.J., Cruz, A.A., Cruz, C.S., Cunha, J., de Jesus, J.V., Fernandes, J., Franco, R.A., Gomes-Filho, I., Lima-Matos, A., Figueiredo, C.A., Lessa, M.A., Lins, L., Mello, L.M., Moura-Santos, P., Muniz, I.S., Paixao-Araujo, I., Pinheiro, G.P., Ponte, E.V., Rodrigues, L.C., Santana, C.V.N., Santos-Lima, G., Souza, T.M.O., Souza-Machado, A., Souza-Machado, C., Stelmach, R., Vasquez, V.S., Adcock, I.M., Ahmed, H., Auffray, C., Bakke, P., Baribaud, F., Bel, E.H., Bigler, J., Bisgaard, H., Boedigheimer, M.J., Bønnelykke, K., Brandsma, J., Brinkman, P., Bucchioni, E., Burg, D., Bush, A., Caruso, M., Chaiboonchoe, A., Chanez, P., Compton, C.H., Corfield, J., D'Amico, A., Dahlén, B., Dahlén, S.E., De Meulder, B., Djukanovic, R., Erpenbeck, V.J., Erzen, D., Fichtner, K., Fitch, N., Fleming, L.J., Formaggio, E., Fowler, S.J., Frey, U., Gahlemann, M., Geiser, T., Goss, V., Guo, Y.-K., Hashimoto, S., Haughney, J., Hedlin, G., Hekking, P.W., Higenbottam, T., Hohlfeld, J.M., Holweg, C., Horváth, I., Howarth, P., James, A.J., Knowles, R.G., Knox, A.J., Krug, N., Lefaudeux, D., Loza, M.J., Lutter, R., Manta, A., Masefield, S., Matthews, J.G., Mazein, A., Meiser, A., Middelveld, R.J.M., Miralpeix, M., Montuschi, P., Mores, N., Murray, C.S., Musial, J., Myles, D., Pahus, L., Pandis, I., Pavlidis, S., Postle, A., Powel, P., Praticò, G., Puig Valls, M., Rao, N., Roberts, A., Roberts, G., Rowe, A., Sandström, T., Schofield, J.P.R., Seibold, W., Selby, A., Shaw, D.E., Sigmund, R., Singer, F., Skipp, P.J., Sousa, A.R., Sterk, P.J., Sun, K., Thornton, B., van Aalderen, W.M., van Geest, M., Vestbo, J., Vissing, N.H., Wagener, A.H., Wagers, S.S., Weiszhart, Z., Wheelock, C.E., Wilson, S.J., Cruz, Alvaro A., Riley, John H., Bansal, Aruna T., Ponte, Eduardo V., Souza-Machado, Adelmir, Almeida, Paula C.A., Biao-Lima, Valmar, Davis, Maggie, Bates, Stewart, Adcock, Ian M., Sterk, Peter J., and Chung, Kian Fan

Published
2020
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6. IL-17–high asthma with features of a psoriasis immunophenotype

Author

Adcock, I.M., Ahmed, H., Auffray, C., Bakke, P., Bansal, A.T., Baribaud, F., Bates, S., Bel, E.H., Bigler, J., Bisgaard, H., Boedigheimer, M.J., Bønnelykke, K., Brandsma, J., Brinkman, P., Bucchioni, E., Burg, D., Bush, A., Caruso, M., Chaiboonchoe, A., Chanez, P., Chung, K.F., Compton, C.H., Corfield, J., D'Amico, A., Dahlen, S.E., De Meulder, B., Djukanovic, R., Erpenbeck, V.J., Erzen, D., Fichtner, K., Fitch, N., Fleming, L.J., Formaggio, E., Fowler, S.J., Frey, U., Gahlemann, M., Geiser, T., Guo, Y., Hashimoto, S., Haughney, J., Hedlin, G., Hekking, P.W., Higenbottam, T., Hohlfeld, J.M., Holweg, C., Horváth, I., Howarth, P., James, A.J., Knowles, R., Knox, A.J., Krug, N., Lefaudeux, D., Loza, M.J., Lutter, R., Manta, A., Masefield, S., Mazein, A., Meiser, A., Middelveld, R.J.M., Miralpeix, M., Montuschi, P., Mores, N., Murray, C.S., Musial, J., Myles, D., Pahus, L., Pandis, I., Pavlidis, S., Powell, P., Praticò, G., Rao, M. Puig N., Riley, J., Roberts, A., Roberts, G., Rowe, A., Sandström, T., Seibold, W., Selby, A., Shaw, D.E., Sigmund, R., Singer, F., Skipp, P.J., Sousa, A.R., Sterk, P.J., Sun, K., Thornton, B., van Aalderen, W.M., van Geest, M., Vestbo, J., Vissing, N.H., Wagener, A.H., Wagers, S.S., Weiszhart, Z., Wheelock, C.E., Wilson, S.J., Aliprantis, Antonios, Allen, David, Alving, Kjell, Badorrek, P., Balgoma, David, Ballereau, S., Barber, Clair, Batuwitage, Manohara Kanangana, Bautmans, A., Bedding, A., Behndig, A.F., Beleta, Jorge, Berglind, A., Berton, A., Bochenek, Grazyna, Braun, Armin, Campagna, D., Carayannopoulos, Leon, Casaulta, C., Chaleckis, Romanas, Dahlén, B., Davison, imothy, De Alba, Jorge, De Lepeleire, Inge, Dekker, Tamara, Delin, Ingrid, Dennison, P., Dijkhuis, Annemiek, Dodson, Paul, Draper, Aleksandra, Dyson, K., Edwards, Jessica, El Hadjam, L., Emma, Rosalia, Ericsson, Magnus, Faulenbach, C., Flood, Breda, Galffy, G., Gallart, Hector, Garissi, D., Gent, J., Gerhardsson de Verdier, M., Gibeon, D., Gomez, Cristina, Gove, Kerry, Gozzard, Neil, Guillmant-Farry, E., Henriksson, E., Hewitt, Lorraine, Hoda, U., Hu, Richard, Hu, Sile, Hu, X., Jeyasingham, E., Johnson, K., Jullian, N., Kamphuis, Juliette, Kennington, Erika J., Kerry, Dyson, Kerry, G., Klüglich, M., Knobel, Hugo, Kolmert, Johan, Konradsen, J.R., Kots, Maxim, Kretsos, Kosmas, Krueger, L., Kuo, Scott, Kupczyk, Maciej, Lambrecht, Bart, Lantz, A.-S., Larminie, Christopher, Larsson, L.X., Latzin, P., Lazarinis, N., Lemonnier, N., Lone-Latif, Saeeda, Lowe, L.A., Manta, Alexander, Marouzet, Lisa, Martin, Jane, Mathon, Caroline, McEvoy, L., Meah, Sally, Menzies-Gow, A., Metcalf, Leanne, Mikus, Maria, Monk, Philip, Naz, Shama, Nething, K., Nicholas, Ben, Nihlén, U., Nilsson, Peter, Niven, R., Nordlund, B., Nsubuga, S., Pacino, Antonio, Palkonen, Susanna, Pellet, J., Pennazza, Giorgio, Petrén, Anne, Pink, Sandy, Pison, C., Postle, Anthony, Rahman-Amin, Malayka, Ravanetti, Lara, Ray, Emma, Reinke, Stacey, Reynolds, Leanne, Riemann, K., Robberechts, Martine, Rocha, J.P., Rossios, C., Russell, Kirsty, Rutgers, Michael, Santini, G., Santoninco, Marco, Saqi, M., Schoelch, Corinna, Schofield, James P.R., Scott, S., Sehgal, N., Sjödin, Marcus, Smids, Barbara, Smith, Caroline, Smith, Jessica, Smith, Katherine M., Söderman, P., Sogbessan, A., Spycher, F., Staykova, Doroteya, Stephan, S., Stokholm, J., Strandberg, K., Sunther, M., Szentkereszty, M., Tamasi, L., Tariq, K., Thörngren, John-Olof, Thorsen, Jonathan, Valente, S., van de Pol, Marianne, van Drunen, C.M., Van Eyll, Jonathan, Versnel, Jenny, Vink, Anton, von Garnier, C., Vyas, A., Wald, Frans, Walker, Samantha, Ward, Jonathan, Wetzel, Kristiane, Wiegman, Coen, Williams, Siân, Yang, Xian, Yeyasingham, Elizabeth, Amgen, W. Yu, Zetterquist, W., Zolkipli, Z., Zwinderman, A.H., Östling, Jörgen, van Geest, Marleen, Jevnikar, Zala, Wilson, Susan, Lutter, Rene, Shaw, Dominick E., Bakke, Per S., Caruso, Massimo, Dahlen, Sven-Erik, Fowler, Stephen J., Horváth, Ildikó, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Sandström, Thomas, Sun, Kai, Pandis, Ioannis, Auffray, Charles, Sousa, Ana R., Guo, Yike, Adcock, Ian M., Howarth, Peter, Chung, Kian Fan, Bigler, Jeanette, Sterk, Peter J., Skipp, Paul J., Djukanović, Ratko, and Vaarala, Outi

Published
2019
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7. Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation

Author

Adcock, I.M., Ahmed, H., Auffray, C., Bakke, P., Bansal, A.T., Baribaud, F., Bates, S., Bel, E.H., Bigler, J., Bisgaard, H., Boedigheimer, M.J., Bønnelykke, K., Brandsma, J., Brinkman, P., Bucchioni, E., Burg, D., Bush, A., Caruso, M., Chaiboonchoe, A., Chanez, P., Chung, F.K., Compton, C.H., Corfield, J., D'Amico, A., Dahlen, S.E., De Meulder, B., Djukanovic, R., Erpenbeck, V.J., Erzen, D., Fichtner, K., Fitch, N., Fleming, L.J., Formaggio, E., Fowler, S.J., Frey, U., Gahlemann, M., Geiser, T., Goss, V., Guo, Y., Hashimoto, S., Haughney, J., Hedlin, G., Hekking, P.W., Higenbottam, T., Hohlfeld, J.M., Holweg, C., Horváth, I., James, A.J., Knowles, R., Knox, A.J., Krug, N., Lefaudeux, D., Loza, M.J., Manta, A., Matthews, J.G., Mazein, A., Meiser, A., Middelveld, R.J.M., Miralpeix, M., Montuschi, P., Mores, N., Murray, C.S., Musial, J., Myles, D., Pahus, L., Pandis, I., Pavlidis, S., Postle, A., Powel, P., Praticò, G., Rao, N., Riley, J., Roberts, A., Roberts, G., Rowe, A., Sandström, T., Schofield, J.P.R., Seibold, W., Selby, A., Shaw, D.E., Sigmund, R., Singer, F., Skipp, P.J., Sousa, A.R., Sterk, P.J., Sun, K., Thornton, B., van Aalderen, W.M., van Geest, M., Vestbo, J., Vissing, N.H., Wagener, A.H., Wagers, S.S., Weiszhart, Z., Wheelock, C.E., Wilson, S.J., Jevnikar, Zala, Östling, Jörgen, Ax, Elisabeth, Calvén, Jenny, Thörn, Kristofer, Israelsson, Elisabeth, Öberg, Lisa, Singhania, Akul, Lau, Laurie C.K., Wilson, Susan J., Ward, Jonathan A., Chauhan, Anoop, Sousa, Ana R., De Meulder, Bertrand, Loza, Matthew J., Baribaud, Frédéric, Sterk, Peter J., Chung, Kian Fan, Sun, Kai, Guo, Yike, Adcock, Ian M., Payne, Debbie, Dahlen, Barbro, Chanez, Pascal, Shaw, Dominick E., Krug, Norbert, Hohlfeld, Jens M., Sandström, Thomas, Djukanovic, Ratko, James, Anna, Hinks, Timothy S.C., Howarth, Peter H., Vaarala, Outi, van Geest, Marleen, and Olsson, Henric

Published
2019
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14. Collided ribosome in a disome unit from S. cerevisiae

Author

Best, K.M., primary, Ikeuchi, K., additional, Kater, L., additional, Best, D.M., additional, Musial, J., additional, Matsuo, Y., additional, Berninghausen, O., additional, Becker, T., additional, Inada, T., additional, and Beckmann, R., additional

Published
2023
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19. Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation

Author

Mikus, M.S. Kolmert, J. Andersson, L.I. Östling, J. Knowles, R.G. Gómez, C. Ericsson, M. Thörngren, J.-O. Khoonsari, P.E. Dahlén, B. Kupczyk, M. de Meulder, B. Auffray, C. Bakke, P.S. Beghe, B. Bel, E.H. Caruso, M. Chanez, P. Chawes, B. Fowler, S.J. Gaga, M. Geiser, T. Gjomarkaj, M. Horváth, I. Howarth, P.H. Johnston, S.L. Joos, G. Krug, N. Montuschi, P. Musial, J. Niżankowska-Mogilnicka, E. Olsson, H.K. Papi, A. Rabe, K.F. Sandström, T. Shaw, D.E. Siafakas, N.M. Uhlén, M. Riley, J.H. Bates, S. Middelveld, R.J.M. Wheelock, C.E. Chung, K.F. Adcock, I.M. Sterk, P.J. Djukanovic, R. Nilsson, P. Dahlén, S.-E. James, A. Ahmed, H. Balgoma, D. Bansal, A.T. Baribaud, F. Bigler, J. Billing, B. Bisgaard, H. Boedigheimer, M.J. Bønnelykke, K. Brandsma, J. Brinkman, P. Bucchioni, E. Burg, D. Bush, A. Chaiboonchoe, A. Checa, T. Compton, C.H. Corfield, J. Cunoosamy, D. D’Amico, A. Emma, R. Erpenbeck, V.J. Erzen, D. Fichtner, K. Fitch, N. Fleming, L.J. Formaggio, E. Frey, U. Gahlemann, M. Goss, V. Guo, Y.-K. Hashimoto, S. Haughney, J. Hedlin, G. Hekking, P.-P.W. Higenbottam, T. Hohlfeld, J.M. Holweg, C.T.J. Knox, A.J. Konradsen, J. Lazarinis, N. Lefaudeux, D. Li, T. Loza, M.J. Lutter, R. Manta, A. Masefield, S. Matthews, J.G. Mazein, A. Meiser, A. Miralpeix, M. Mores, N. Murray, C.S. Myles, D. Naz, S. Nordlund, B. Pahus, L. Pandis, I. Pavlidis, S. Postle, A. Powel, P. Rao, N. Reinke, S. Roberts, A. Roberts, G. Rowe, A. Schofield, J.P.R. Seibold, W. Selby, A. Sigmund, R. Singer, F. Sjödin, M. Skipp, P.J. Sousa, A.R. Sun, K. Thornton, B. Uddin, M. van Aalderen, W.M. van Geest, M. Vestbo, J. Vissing, N.H. Wagener, A.H. Wagers, S.S. Weiszhart, Z. Wheelock, C.E. Wheelock, Å. Wilson, S.J. Yasinska, V. Brusselle, G.G. Campbell, D.A. Contoli, M. Damm, K. de Rudder, I. Delin, I. Devautour, C. Duplaga, M. Eduards, M. Ek, A. Ekström, T. Figiel, E. Gaber, F. Gauw, S. Gawlewicz-Mroczka, A. Gerding, D. Haque, S. Hewitt, L. Hiemstra, P.S. Holgate, S.T. Holloway, J. Kania, A. Kanniess, F. Karlsson, Ö. Kips, J.C. Kumlin, M. Lantz, A.-S. Lazarinis, N. Magnussen, H. Mallia, P. Martling, I. Meziane, L. Oikonomidou, E. Olsson, M. Pace, E. Papadopouli, E. Papadopoulos, N. Plataki, M. Profita, M. Reinius, L.E. Richter, K. Robinson, D.S. Romagnoli, M. Samara, K. Schelfhout, V. Skedinger, M. Stamataki, E. ten Brinke, A. Vachier, I. Wallén-Nielsen, E. van Veen, I. Weersink, E. Wilson, S.J. Yasinska, V. Zervas, E. Ziolkowska-Graca, B. U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcome) Study Group BIOAIR (Longitudinal Assessment of Clinical Course Biomarkers in Severe Chronic Airway Disease) Consortium

Abstract

Rationale Asthma phenotyping requires novel biomarker discovery. Objectives To identify plasma biomarkers associated with asthma phenotypes by application of a new proteomic panel to samples from two well-characterised cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, COPD subjects and healthy controls (HCs). Methods An antibody-based array targeting 177 proteins predominantly involved in pathways relevant to inflammation, lipid metabolism, signal transduction and extracellular matrix was applied to plasma from 525 asthmatics and HCs in the U-BIOPRED cohort, and 142 subjects with asthma and COPD from the validation cohort BIOAIR. Effects of oral corticosteroids (OCS) were determined by a 2-week, placebo-controlled OCS trial in BIOAIR, and confirmed by relation to objective OCS measures in U-BIOPRED. Results In U-BIOPRED, 110 proteins were significantly different, mostly elevated, in SA compared to MMA and HCs. 10 proteins were elevated in SA versus MMA in both U-BIOPRED and BIOAIR (alpha-1-antichymotrypsin, apolipoprotein-E, complement component 9, complement factor I, macrophage inflammatory protein-3, interleukin-6, sphingomyelin phosphodiesterase 3, TNF receptor superfamily member 11a, transforming growth factor-β and glutathione S-transferase). OCS treatment decreased most proteins, yet differences between SA and MMA remained following correction for OCS use. Consensus clustering of U-BIOPRED protein data yielded six clusters associated with asthma control, quality of life, blood neutrophils, high-sensitivity C-reactive protein and body mass index, but not Type-2 inflammatory biomarkers. The mast cell specific enzyme carboxypeptidase A3 was one major contributor to cluster differentiation. Conclusions The plasma proteomic panel revealed previously unexplored yet potentially useful Type-2independent biomarkers and validated several proteins with established involvement in the pathophysiology of SA. © 2022 European Respiratory Society. All rights reserved.

Published
2022

20. Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation

Author

Mikus MS, Kolmert J, Andersson LI, Östling J, Knowles RG, Gómez C, Ericsson M, Thörngren JO, Khoonsari PE, Dahlén B, Kupczyk M, De Meulder B, Auffray C, Bakke PS, Beghe B, Bel EH, Caruso M, Chanez P, Chawes B, Fowler SJ, Gaga M, Geiser T, Gjomarkaj M, Horváth I, Howarth PH, Johnston SL, Joos G, Krug N, Montuschi P, Musial J, Ni?ankowska-Mogilnicka E, Olsson HK, Papi A, Rabe KF, Sandström T, Shaw DE, Siafakas NM, Uhlen M, Riley JH, Bates S, Middelveld RJM, Wheelock CE, Chung KF, Adcock IM, Sterk PJ, Djukanovic R, Nilsson P, Dahlén SE, James A, U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcome) Study Group, BIOAIR (Longitudinal Assessment of Clinical Course, and Biomarkers in Severe Chronic Airway Disease) Consortium.

Subjects
Inflammation, Steroids, Asthma
Abstract

Rationale: Asthma phenotyping requires novel biomarker discovery. Objectives: To identify plasma biomarkers associated with asthma phenotypes by application of a new proteomic panel to samples from two well-characterized cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, chronic obstructive pulmonary disease (COPD) subjects and healthy controls (HC). Methods: An antibody-based array targeting 177 proteins predominantly involved in pathways relevant to inflammation, lipid metabolism, signal transduction and extracellular matrix was applied to plasma from 525 asthmatics and HC in the U-BIOPRED cohort, and 142 subjects with asthma and COPD from the validation cohort BIOAIR. Effects of oral corticosteroids (OCS) were determined by a two-week, placebo-controlled OCS trial in BIOAIR, and confirmed by relation to objective OCS measures in U-BIOPRED. Results: In U-BIOPRED, 110 proteins were significantly different, mostly elevated, in SA compared to MMA and HC. Ten proteins were elevated in SA versus MMA in both U-BIOPRED and BIOAIR (alpha-1-antichymotrypsin, apolipoprotein-E, complement component 9, complement factor I, macrophage inflammatory protein-3, interleukin-6, sphingomyelin phosphodiesterase 3, RANK, TGF-?1, and glutathione S-transferase). OCS treatment decreased most proteins, yet differences between SA and MMA remained following correction for OCS use. Consensus clustering of U-BIOPRED protein data yielded six clusters associated with asthma control, quality of life, blood neutrophils, hsCRP, and BMI, but not Type-2 inflammatory biomarkers. The mast cell specific enzyme carboxypeptidase A3 was one major contributor to cluster differentiation. Conclusions: The plasma proteomic panel revealed previously unexplored yet potentially useful Type-2-independent biomarkers, and validated several proteins with established involvement in the pathophysiology of severe asthma.

Published
2022

21. Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation

Author

Mikus, M. S., Kolmert, J., Andersson, L. I., Ostling, J., Knowles, R. G., Gomez, C., Ericsson, M., Thorngren, J. -O., Khoonsari, P. E., Dahlen, B., Kupczyk, M., de Meulder, B., Auffray, C., Bakke, P. S., Beghe, Bianca, Bel, E. H., Caruso, M., Chanez, P., Chawes, B., Fowler, S. J., Gaga, M., Geiser, T., Gjomarkaj, M., Horvath, I., Howarth, P. H., Johnston, S. L., Joos, G., Krug, N., Montuschi, P., Musial, J., Nizankowska-Mogilnicka, E., Olsson, H. K., Papi, A., Rabe, K. F., Sandstrom, T., Shaw, D. E., Siafakas, N. M., Uhlen, M., Riley, J. H., Bates, S., Middelveld, R. J. M., Wheelock, C. E., Chung, K. F., Adcock, I. M., Sterk, P. J., Djukanovic, R., Nilsson, P., Dahlen, S. -E., James, A., Ahmed, H., Balgoma, D., Bansal, A. T., Baribaud, F., Bigler, J., Billing, B., Bisgaard, H., Boedigheimer, M. J., Bonnelykke, K., Brandsma, J., Brinkman, P., Bucchioni, E., Burg, D., Bush, A., Chaiboonchoe, A., Checa, T., Compton, C. H., Corfield, J., Cunoosamy, D., D'Amico, A., Emma, R., Erpenbeck, V. J., Erzen, D., Fichtner, K., Fitch, N., Fleming, L. J., Formaggio, E., Frey, U., Gahlemann, M., Goss, V., Guo, Y. -K., Hashimoto, S., Haughney, J., Hedlin, G., Hekking, P. -P. W., Higenbottam, T., Hohlfeld, J. M., Holweg, C. T. J., Knox, A. J., Konradsen, J., Lazarinis, N., Lefaudeux, D., Li, T., Loza, M. J., Lutter, R., Manta, A., Masefield, S., Matthews, J. G., Mazein, A., Meiser, A., Miralpeix, M., Mores, N., Murray, C. S., Myles, D., Naz, S., Nordlund, B., Pahus, L., Pandis, I., Pavlidis, S., Postle, A., Powel, P., Rao, N., Reinke, S., Roberts, A., Roberts, G., Rowe, A., Schofield, J. P. R., Seibold, W., Selby, A., Sigmund, R., Singer, F., Sjodin, M., Skipp, P. J., Sousa, A. R., Sun, K., Thornton, B., Uddin, M., van Aalderen, W. M., van Geest, M., Vestbo, J., Vissing, N. H., Wagener, A. H., Wagers, S. S., Weiszhart, Z., Wheelock, A., Wilson, S. J., Yasinska, V., Brusselle, G. G., Campbell, D. A., Contoli, M., Damm, K., de Rudder, I., Delin, I., Devautour, C., Duplaga, M., Eduards, M., Ek, A., Ekstrom, T., Figiel, E., Gaber, F., Gauw, S., Gawlewicz-Mroczka, A., Gerding, D., Haque, S., Hewitt, L., Hiemstra, P. S., Holgate, S. T., Holloway, J., Kania, A., Kanniess, F., Karlsson, O., Kips, J. C., Kumlin, M., Lantz, A. -S., Magnussen, H., Mallia, P., Martling, I., Meziane, L., Oikonomidou, E., Olsson, M., Pace, E., Papadopouli, E., Papadopoulos, N., Plataki, M., Profita, M., Reinius, L. E., Richter, K., Robinson, D. S., Romagnoli, M., Samara, K., Schelfhout, V., Skedinger, M., Stamataki, E., ten Brinke, A., Vachier, I., Wallen-Nielsen, E., van Veen, I., Weersink, E., Zervas, E., and Ziolkowska-Graca, B.

Subjects
Blood Proteins, Humans, Inflammation, Proteomics, Severity of Illness Index, Steroids, Asthma, Quality of Life
Published
2022

27. Medication Adherence in Patients With Severe Asthma Prescribed Oral Corticosteroids in the U-BIOPRED Cohort

Author

Alahmadi, Fahad H., primary, Simpson, Andrew J., additional, Gomez, Cristina, additional, Ericsson, Magnus, additional, Thörngren, John-Olof, additional, Wheelock, Craig E., additional, Shaw, Dominic E., additional, Fleming, Louise J., additional, Roberts, Graham, additional, Riley, John, additional, Bates, Stewart, additional, Sousa, Ana R., additional, Knowles, Richard, additional, Bansal, Aruna T., additional, Corfield, Julie, additional, Pandis, Ioannis, additional, Sun, Kai, additional, Bakke, Per S., additional, Caruso, Massimo, additional, Chanez, Pascal, additional, Dahlén, Barbro, additional, Horvath, Ildiko, additional, Krug, Norbert, additional, Montuschi, Paolo, additional, Singer, Florian, additional, Wagers, Scott, additional, Adcock, Ian M., additional, Djukanovic, Ratko, additional, Chung, Kian Fan, additional, Sterk, Peter J., additional, Dahlen, Sven-Erik, additional, Fowler, Stephen J., additional, Adcock, I.M., additional, Ahmed, H., additional, Auffray, C., additional, Bakke, P., additional, Bansal, A.T., additional, Baribaud, F., additional, Bates, S., additional, Bel, E.H., additional, Bigler, J., additional, Bisgaard, H., additional, Boedigheimer, M.J., additional, Bønnelykke, K., additional, Brandsma, J., additional, Brinkman, P., additional, Bucchioni, E., additional, Burg, D., additional, Bush, A., additional, Caruso, M., additional, Chaiboonchoe, A., additional, Chanez, P., additional, Chung, F.K., additional, Compton, C.H., additional, Corfield, J., additional, D'Amico, A., additional, Dahlèn, B., additional, Dahlén, S.E., additional, De Meulder, B., additional, Djukanovic, R., additional, Erpenbeck, V.J., additional, Erzen, D., additional, Fichtner, K., additional, Fitch, N., additional, Fleming, L.J., additional, Formaggio, E., additional, Fowler, S.J., additional, Frey, U., additional, Gahlemann, M., additional, Geiser, T., additional, Goss, V., additional, Guo, Y., additional, Hashimoto, S., additional, Haughney, J., additional, Hedlin, G., additional, Hekking, P.W., additional, Higenbottam, T., additional, Hohlfeld, J.M., additional, Holweg, C., additional, Horváth, I., additional, Howarth, P., additional, James, A.J., additional, Knowles, R.G., additional, Knox, A.J., additional, Krug, N., additional, Lefaudeux, D., additional, Loza, M.J., additional, Lutter, R., additional, Manta, A., additional, Masefield, S., additional, Matthews, J.G., additional, Mazein, A., additional, Meiser, A., additional, Middelveld, R.J.M., additional, Miralpeix, M., additional, Montuschi, P., additional, Mores, N., additional, Murray, C.S., additional, Musial, J., additional, Myles, D., additional, Pahus, L., additional, Pandis, I., additional, Pavlidis, S., additional, Postle, A., additional, Powel, P., additional, Praticò, G., additional, Valls, M. Puig, additional, Rao, N., additional, Riley, J., additional, Roberts, A., additional, Roberts, G., additional, Rowe, A., additional, Sandström, T., additional, Schofield, J.P.R., additional, Seibold, W., additional, Selby, A., additional, Shaw, D.E., additional, Sigmund, R., additional, Singer, F., additional, Skipp, P.J., additional, Sousa, A.R., additional, Sterk, P.J., additional, Sun, K., additional, Thornton, B., additional, van Aalderen, W.M., additional, van Geest, M., additional, Vestbo, J., additional, Vissing, N.H., additional, Wagener, A.H., additional, Wagers, S.S., additional, Weiszhart, Z., additional, Wheelock, C.E., additional, and Wilson, S.J., additional

Published
2021
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30. Rivaroxaban for thromboprophylaxis after hospitalization for medical illness

Author

Spyropoulos, A, Ageno, W, Albers, G, Elliott, C, Halperin, J, Hiatt, W, Maynard, G, Steg, P, Weitz, J, Suh, E, Spiro, T, Barnathan, E, Raskob, G, Douketis, J, Turpie, A, Schulman, S, Kearon, C, Linkins, L, Schellong, S, Bauer, K, Geerts, W, Roberts, R, Casais, P, Gallus, A, Karrasch, J, Eichinger-Hasenauer, S, Krivenchuk, V, Hadzovic-Dzuvo, A, Trbojevic, S, Lopes, R, Mincheva, V, Carrier, M, Dennis, R, Tudoric, N, Spinar, J, Nielsen, H, Marandi, T, Shaburishvili, T, Beyer-Westendorf, J, Vardas, P, Boda, Z, Brenner, B, Piovella, F, Krievins, D, Petrauskiene, B, Dejanova-Ilijevska, V, Virgen Carrillo, L, Middeldorp, S, Castillo Leon, R, Torbicki, A, Saraiva de Sousa, M, Dorobantu, M, Militaru, C, Yavelov, I, Vuckovic, B, Reuter, H, Basson, M, Monreal, M, Kucukoglu, S, Parkhomenko, A, Alikhan, R, Rosenberg, D, Yusen, R, Khorana, A, Tapson, V, Pollack, C, Hazelrigg, M, Jure, H, Alvarisqueta, A, Cartasegna, L, Hominal, M, Cursack, G, Alzogaray, M, Maillo, M, Parody, M, Caccavo, A, Dran, R, Muntaner, J, Casas, M, Schmidberg, J, Sarjanovich, R, Gabito, A, Garrido, M, Amuchastegui, M, Fernandez, A, Loureyro, J, Giumelli, C, Heazlewood, V, Colquhoun, D, White, H, Sabet, A, Bowler, S, Carroll, P, Khalafallah, A, Baker, R, Hedger, S, Simpson, F, Jackson, D, Chong, B, Siostrzonek, P, Gary, T, Hoppe, U, Dosta, N, Prystrom, A, Gorokhovsky, S, Yanushko, V, Skrahin, A, Kulik, A, Maslianski, B, Yakubtsevich, R, Timkin, I, Moguchaya, O, Tanaskovic, N, Miljkovic, S, Stojkovic, S, Kovacevic-Preradovic, T, Jovic, D, Basagic, E, Radjen, M, Mutapcic, M, Rizvanovic-Vojic, E, Galic, K, Terzic, I, Pojskic, B, Stevanovic, D, Cehajic, M, Rech, R, Annichino-Bizzacchi, J, Stelmach, R, Blanco, D, Castro, I, Backes, L, Saraiva, J, Ramacciotti, E, de Barros e Silva, P, Reis, G, Moreira Vieira, E, Leaes, P, Zimmermann, S, Van Bellen, B, Precoma, D, Luiz Silvestrini, T, Hernandes, M, Kyoleyan, M, Kalinova, T, Tiholov, R, Petrov, I, Mihov, A, Chompalova, B, Velikov, C, Pencheva, G, Atanasov, P, Raev, D, Kinova, E, Peltegov, V, Marchev, S, Siulemezova, S, Ayryanova, I, Grigorov, M, Naydenova, I, Koteva, N, Dimov, B, Runev, N, Getov, D, Metev, H, Donchev, K, Taseva, M, Hadzhieva, A, Benov, H, Stoyanov, M, Tisheva-Gospodinova, S, Mihaylova, N, Abadzhiev, S, Atzev, B, Georgiev, R, Mollov, M, Stoikov, A, Mazhdrakov, G, Karastanev, K, Dube, F, Roth, S, Mansour, S, Wu, C, Dolan, S, Pesant, Y, Pietrangelo, M, Dresser, G, Kahn, S, Kruisselbrink, R, Cadena Bonfanti, A, Botero, R, Quintero Ossa, A, Poveda, C, Cedano, J, Gomez Isaza, L, Villaquiran Torres, C, Gomez Mesa, J, Vargas Alonso, R, Espinosa, D, Rodriguez, J, Sanchez, G, Accini Mendoza, J, Gomez Florez, C, Cuervo Millan, F, Pesek, K, Horvat, D, Fuckar, K, Ruzic, A, Ostricki, B, Knezevic, A, Breitenfeld, T, Laganovic, M, Samodol, A, Sikic, J, Starcevic, B, Babic, Z, Samarzija, M, Milas, K, Votocek, S, Kvapil, M, Kolman, P, Bindas, P, Simon, V, Adamek, T, Svobodova, J, Gergely, L, Lastuvka, J, Macel, I, Navratil, K, Gregor, P, Lacnak, B, Janousek, J, Kellnerova, I, Hulinsky, V, Matusek, Z, Prucek, L, Dunaj, M, Pirchala, M, Vencour, D, Pavolko, M, Gorican, K, Fiksa, J, Tuxen, C, Meyer, C, Suppli Ulrik, C, Uuetoa, T, Otarishvili, N, Khintibidze, I, Emukhvari, N, Kipiani, Z, Gochitashvili, D, Mamatsashvili, M, Megreladze, I, Paposhvili, K, Agladze, R, Eradze, Z, Chelidze, K, Lominadze, S, Chukhrukidze, A, Chumburidze, V, Metreveli, S, Danelia, V, Orjonikidze, S, Kobulia, B, Nikolaishvili, G, Gvenetadze, R, Melia, A, Tsinamdzgvrishvili, B, Sekhniashvili, M, Sikharulidze, I, Meuser, M, Licka, M, Rauch-Kroehnert, U, Graf, K, Brachmann, J, Akin, I, Toumbis, M, Vassilikos, V, Konstantinides, S, Steiropoulos, P, Gogos, C, Andrikopoulos, G, Parthenakis, F, Karydi, P, Tsivgoulis, G, Mertzanos, G, Olympios, C, Karapanayiotides, T, Paraskevopoulou, E, Kifnidis, K, Hahalis, G, Skoutelis, A, Vadikolias, K, Nyirati, G, Nagy, L, Matoltsy, A, Komoly, S, Lippai, J, Kiss, K, Toth, K, Pozsegovits, K, Kiraly, C, Bereczki, D, Zolyomi, S, Szakal, I, Pall, D, Futo, L, Forster, T, Lovasz, O, Papp, A, Kiraly, Z, Pozsonyi, Z, Hajko, E, Kristof, P, Lakatos, F, Ples, Z, Kirschner, R, Lupkovics, G, Timar, G, Pinter, I, Kristof, T, Kis, E, Kovacs, A, Jakab, G, Palinkas, A, Muller, G, Turi, T, Horvath, C, Kondakor, I, Csanyi, A, Frankfurter, Z, Gurzo, M, Gafter-Gvili, A, Kuchuk, M, Azzam, Z, Elis, A, Halabi, M, Hussein, O, Blum, A, Tsoran-Rosenthal, I, Lishner, M, Hochberg-Klein, S, Caraco, Y, Atar, S, Elias, N, Gavish, D, Butnaru, A, Cosmi, F, Garbelotto, R, Giorgi Pierfranceschi, M, Simioni, L, Gronda, E, Pesci, A, D'Angelo, A, Fedele, F, Ghirarduzzi, A, Piovaccari, G, Lembo, G, Ria, L, Monaco, G, Brunelli, C, Tosetto, A, Capucci, A, Zanatta, N, Pistolesi, M, Mazzi, V, Testa, S, Scherillo, M, Di Biase, M, Antonicelli, R, Lodigiani, C, Nassiacos, D, Viksne, I, Lapkovska, Z, Rancane, G, Sime, I, Pontaga, N, Eglite, R, Puzule, S, Smolova, R, Butkiene, Z, Bagdonas, A, Raugaliene, R, Norkiene, S, Norviliene, R, Basijokiene, V, Stonkus, S, Griskeviciene, V, Miskiniene, A, Norvaisiene, R, Skripkauskiene, I, Jovkovska-Kaeva, B, Kochovska-Kamchevska, N, Antovski, A, Nechevska, L, Celeska, V, Ilievska-Poposka, B, Kostojchinoska, M, Donchovska, S, Kedev, S, Kuzmanovski, I, Bushletikj, O, Stojchev, S, Bakrachevski, N, Kuzmanovska, B, Angusheva, T, Llamas Esperon, G, Valdez Lopez, H, Medina Pech, C, Cortes Hernandez, M, Gans, S, Smulders, S, Swart, H, Boersma, W, Goosens, M, Hovens, M, Semplonius, G, Sohne, M, Lema Osores, J, Salas Perez, M, Rodriguez, A, Rios Oliva, C, Cotrina, R, Berrospi Argandona, P, Toce Yanez, L, Chavez Ayala, C, Mirek-Bryniarska, E, Goch, A, Skucha, W, Skorski, M, Miekus, P, Szyszka, A, Piotrowski, G, Gniot, J, Czerski, T, Debich, P, Zaluska, R, Bebenek, W, Wozakowska-Kaplon, B, Sciborski, R, Ilkowski, J, Wojnowski, P, Uscinska, E, Gaciong, Z, Bonek, R, Sobkowicz, B, Berkowski, P, Bejgier, K, Polonski, L, Kosior, D, Lata, S, Kolodziej, P, Gessek, J, Kachel, T, Talalaj, M, Musial, J, Lewczuk, J, Krysiak, W, Kucharski, L, Wysokinski, A, Minc, P, Martinez, J, Gregorio, T, Almeida, F, Monteiro, P, Stanciulescu, G, Mercea, C, Iosipescu, L, Ciobotaru, V, Crisu, D, Burca, M, Tudoran, M, Savu, A, Negrean, V, Cojocaru, C, Minescu, B, Popa, V, Blajan, D, Nastase-Melicovici, D, Fruntelata, A, Barbulescu, S, Lukinyh, L, Akhunova, S, Vishneva, E, Semenova, I, Nikolaev, K, Shaydyuk, O, Nilk, R, Shalnev, V, Apartsin, K, Goloshchekin, B, Shpagina, L, Khlevchuk, T, Arkhipov, M, Malygin, A, Shvarts, Y, Khaisheva, L, Popov, D, Kobalava, Z, Lipchenko, A, Shapovalova, Y, Zrazhevsky, K, Greshnova, I, Maslova, N, Karabenenko, A, Shogenov, Z, Budankova, E, Barbarash, O, Uspenskiy, Y, Kosmacheva, E, Berns, S, Kostenko, V, Zateyshchikov, D, Vishnevsky, A, Boldueva, S, Podzolkov, V, Sergeeva, E, Grinshtein, Y, Khrustalev, O, Bugrova, O, Repin, A, Andreev, D, Petrovic, P, Boskovic Matic, T, Apostolovic, S, Lazic, Z, Stankovic, D, Stankovic, A, Mitov, V, Sofronic, D, Kopitovic, I, Zdravkovic, V, Joksimovic, Z, Lazovic, N, Petrovic-Stanojevic, N, Ilic, A, Vujadinovic, O, Pencic-Popovic, B, Andjelkovic, N, Sekularac, N, Hinic, S, Radjen, G, Zivkovic, A, Putnikovic, B, Ivanov, I, Babic, R, Van Zyl, L, Hobson, B, Engelbrecht, J, Mitha, I, Siebert, H, Jacobson, B, Breedt, J, Prozesky, H, Ntsekhe, M, Bayat, J, Ellis, G, Tarr, G, Adler, D, Van Dyk, C, Ismail, S, Spargo, C, Abdool-Gaffar, M, Saaiman, J, Venter, K, Lorente Aroca, M, Fernandez Portales, F, Pedrajas Navas, J, Rodriguez Botaro, A, Santa Cruz Siminiani, A, Lopez Reyes, R, Bisbe i Company, J, Piedecausa Selfa, M, Velasco Garrido, J, Sobrino-Martinez, J, Munoz Delgado, G, Sala Llinas, E, Blanco Coronado, J, Almenar Bonet, L, Vida Gutierrez, M, Sanchez Lora, F, Sanchez Martinez, R, Calderon, E, Villalta Blanch, J, De la Hera Galarza, J, Bustamante Ruiz, A, Garcia-Fuster, M, Ripoll Vera, T, Alvarez-Sala Walter, L, Todoli Parra, J, Diaz Fernandez, J, Bosa Ojeda, F, Pellicer-Ciscar, C, Jara Palomares, L, Quiles Granado, J, Trigo Bautista, A, Ruiz Bustillo, S, Ordi Ros, J, Tolosa-Vilella, C, Marin Ortuno, F, Garcia Sanchez, F, Barba Martin, R, Segovia Cubero, J, Cuervas-Mons Martinez, V, Galan Montejano, M, Lopez Meseguer, M, Sener Comert, S, Koksal, N, Tertemiz, K, Ernam, D, Dursun, A, Yildiz, O, Rudenko, L, Abrahamovych, O, Goloborodko, A, Holovchenko, N, Kulyk, A, Yagensky, A, Batushkin, V, Zolotaikina, V, Kozyolkin, O, Faynyk, A, Maslovskyy, V, Petrovskyy, R, Koshlia, V, Chopey, I, Burmak, I, Malynovsky, Y, Voronkov, L, Karpenko, O, Dziublyk, O, Godlevska, O, Borovyk, V, Bezrodna, L, Serik, S, Ovsyannikova, N, Vynnychenko, L, Kopytsya, M, Rudkovskiy, V, Grishyna, O, Vyshnyvetskyy, I, Prystupa, L, Tseluyko, V, Perepeliuk, M, Koval, O, Sychov, O, Church, A, Goudie, A, Elliott, M, Ferguson, C, Welker, J, Kao, C, Bhagwat, R, Serota, H, Bozorgchami, H, Nambiar, R, Spilseth, S, Bhagwath, G, Syed, F, Morrow, L, Updegrove, J, Bercz, P, Kambo, V, Henderson, D, Wright, P, Dang, N, Nadar, V, Jaffrani, N, El-Shahawy, M, Grossman, C, Pearle, J, Weinstein, D, Galanis, T, Gazmuri, R, Kastelic, R, Martinez, R, Laman, D, Macchiavelli, A, Kmetzo, J, Thurm, C, Kayembe, T, Chandrashekhar, Y, Bassetti, D, Jaoude, P, Williams, H, Dewhurst, R, Naqvi, S, Burr, J, Rodriguez-Cintron, W, Jeanfreau, R, Kosinski, E, Ndukwu, I, Sotolongo, C, Daboul, N, Wilmer, C, Simon, P, Tak, T, Rees, C, Gupta, N, Lerner, R, Graffagnino, C, Reed, R, Alford, C, Mody, F, Wellmon, B, Hamroff, G, Rajan, R, Kaatz, S, Spyropoulos A. C., Ageno W., Albers G. W., Elliott C. G., Halperin J. L., Hiatt W. R., Maynard G. A., Steg P. G., Weitz J. I., Suh E., Spiro T. E., Barnathan E. S., Raskob G. E., Douketis J., Turpie A. G., Schulman S., Kearon C., Linkins L. A., Schellong S., Bauer K., Geerts W., Roberts R., Casais P., Gallus A., Karrasch J., Eichinger-Hasenauer S., Krivenchuk V., Hadzovic-Dzuvo A., Trbojevic S., Lopes R., Mincheva V., Carrier M., Dennis R., Tudoric N., Spinar J., Nielsen H., Marandi T., Shaburishvili T., Beyer-Westendorf J., Vardas P., Boda Z., Brenner B., Piovella F., Krievins D., Petrauskiene B., Dejanova-Ilijevska V., Virgen Carrillo L. R., Middeldorp S., Castillo Leon R. P., Torbicki A., Saraiva de Sousa M., Dorobantu M., Militaru C., Yavelov I., Vuckovic B., Reuter H., Basson M., Monreal M., Kucukoglu S., Parkhomenko A., Alikhan R., Rosenberg D., Yusen R., Khorana A., Tapson V., Pollack C., Hazelrigg M., Jure H., Alvarisqueta A., Cartasegna L., Hominal M., Cursack G., Alzogaray M., Maillo M., Parody M., Caccavo A., Dran R. D., Muntaner J. A., Casas M., Schmidberg J., Sarjanovich R., Gabito A., Garrido M., Amuchastegui M., Fernandez A., Loureyro J., Giumelli C., Heazlewood V., Colquhoun D., White H., Sabet A., Bowler S., Carroll P., Khalafallah A., Baker R., Hedger S., Simpson F. G., Jackson D., Chong B., Siostrzonek P., Gary T., Hoppe U., Dosta N., Prystrom A., Gorokhovsky S., Yanushko V., Skrahin A., Kulik A., Maslianski B., Yakubtsevich R., Timkin I., Moguchaya O., Tanaskovic N., Miljkovic S., Stojkovic S., Kovacevic-Preradovic T., Jovic D., Basagic E., Radjen M., Mutapcic M., Rizvanovic-Vojic E., Galic K., Terzic I., Pojskic B., Stevanovic D., Cehajic M., Rech R., Annichino-Bizzacchi J., Stelmach R., Blanco D., Castro I., Backes L. M., Saraiva J. F., Ramacciotti E., de Barros e Silva P. G. M., Reis G., Moreira Vieira E., Leaes P., Zimmermann S., Van Bellen B., Precoma D., Luiz Silvestrini T., Hernandes M. E., Kyoleyan M., Kalinova T., Tiholov R., Petrov I., Mihov A., Chompalova B., Velikov C., Pencheva G., Atanasov P., Raev D., Kinova E., Peltegov V., Marchev S., Siulemezova S., Ayryanova I. D., Grigorov M., Naydenova I., Koteva N., Dimov B., Runev N., Getov D., Metev H., Donchev K., Taseva M., Hadzhieva A., Benov H., Stoyanov M., Tisheva-Gospodinova S., Mihaylova N., Abadzhiev S., Atzev B., Georgiev R., Mollov M., Stoikov A., Mazhdrakov G., Karastanev K., Dube F., Roth S., Mansour S., Wu C., Dolan S., Pesant Y., Pietrangelo M., Dresser G., Kahn S., Kruisselbrink R., Cadena Bonfanti A., Botero R., Quintero Ossa A., Poveda C. M., Cedano J., Gomez Isaza L., Villaquiran Torres C., Gomez Mesa J., Vargas Alonso R., Espinosa D., Rodriguez J. M., Sanchez G., Accini Mendoza J. L., Gomez Florez C. C., Cuervo Millan F., Pesek K., Horvat D., Fuckar K., Ruzic A., Ostricki B., Knezevic A., Breitenfeld T., Laganovic M., Samodol A., Sikic J., Starcevic B., Babic Z., Samarzija M., Milas K., Votocek S., Kvapil M., Kolman P., Bindas P., Simon V., Adamek T., Svobodova J., Gergely L., Lastuvka J., Macel I., Navratil K., Gregor P., Lacnak B., Janousek J., Kellnerova I., Hulinsky V., Matusek Z., Prucek L., Dunaj M., Pirchala M., Vencour D., Pavolko M., Gorican K., Fiksa J., Tuxen C., Meyer C., Suppli Ulrik C., Uuetoa T., Otarishvili N., Khintibidze I., Emukhvari N., Kipiani Z., Gochitashvili D., Mamatsashvili M., Megreladze I., Paposhvili K., Agladze R., Eradze Z., Chelidze K., Lominadze S., Chukhrukidze A., Chumburidze V., Metreveli S., Danelia V., Orjonikidze S., Kobulia B., Nikolaishvili G., Gvenetadze R., Melia A., Tsinamdzgvrishvili B., Sekhniashvili M., Sikharulidze I., Meuser M., Licka M., Rauch-Kroehnert U., Graf K., Brachmann J., Akin I., Toumbis M., Vassilikos V., Konstantinides S., Steiropoulos P., Gogos C., Andrikopoulos G., Parthenakis F., Karydi P., Tsivgoulis G., Mertzanos G., Olympios C., Karapanayiotides T., Paraskevopoulou E., Kifnidis K., Hahalis G., Skoutelis A., Vadikolias K., Nyirati G., Nagy L., Matoltsy A., Komoly S., Lippai J., Kiss K., Toth K., Pozsegovits K., Kiraly C., Bereczki D., Zolyomi S., Szakal I., Pall D., Futo L., Forster T., Lovasz O., Papp A., Kiraly Z., Pozsonyi Z., Hajko E., Kristof P., Lakatos F., Ples Z., Kirschner R., Lupkovics G., Timar G., Pinter I., Kristof T., Kis E., Kovacs A., Jakab G., Palinkas A., Muller G., Turi T., Horvath C., Kondakor I., Csanyi A., Frankfurter Z., Gurzo M., Gafter-Gvili A., Kuchuk M., Azzam Z., Elis A., Halabi M., Hussein O., Blum A., Tsoran-Rosenthal I., Lishner M., Hochberg-Klein S., Caraco Y., Atar S., Elias N., Gavish D., Butnaru A., Cosmi F., Garbelotto R., Giorgi Pierfranceschi M., Simioni L., Gronda E., Pesci A., D'Angelo A., Fedele F., Ghirarduzzi A., Piovaccari G., Lembo G., Ria L., Monaco G. L., Brunelli C., Tosetto A., Capucci A., Zanatta N., Pistolesi M., Mazzi V., Testa S., Scherillo M., Di Biase M., Antonicelli R., Lodigiani C., Nassiacos D., Viksne I., Lapkovska Z., Rancane G., Sime I., Pontaga N., Eglite R., Puzule S., Smolova R., Butkiene Z., Bagdonas A., Raugaliene R., Norkiene S., Norviliene R., Basijokiene V., Stonkus S., Griskeviciene V., Miskiniene A., Norvaisiene R., Skripkauskiene I., Jovkovska-Kaeva B., Kochovska-Kamchevska N., Antovski A., Nechevska L., Celeska V., Ilievska-Poposka B., Kostojchinoska M., Donchovska S., Kedev S., Kuzmanovski I., Bushletikj O., Stojchev S., Bakrachevski N., Kuzmanovska B., Angusheva T., Llamas Esperon G., Valdez Lopez H., Medina Pech C., Cortes Hernandez M., Virgen Carrillo L., Gans S., Smulders S., Swart H., Boersma W., Goosens M., Hovens M., Semplonius G., Sohne M., Lema Osores J., Salas Perez M. D., Rodriguez A., Rios Oliva C., Cotrina R., Berrospi Argandona P., Toce Yanez L., Chavez Ayala C., Mirek-Bryniarska E., Goch A., Skucha W., Skorski M., Miekus P., Szyszka A., Piotrowski G., Gniot J., Czerski T., Debich P., Zaluska R., Bebenek W., Wozakowska-Kaplon B., Sciborski R., Ilkowski J., Wojnowski P., Uscinska E., Gaciong Z., Bonek R., Sobkowicz B., Berkowski P., Bejgier K., Polonski L., Kosior D., Lata S., Kolodziej P., Gessek J., Kachel T., Talalaj M., Musial J., Lewczuk J., Krysiak W., Kucharski L., Wysokinski A., Minc P., Martinez J., Gregorio T., Almeida F., Monteiro P., Stanciulescu G., Mercea C. D., Iosipescu L. C., Ciobotaru V., Crisu D., Burca M., Tudoran M., Savu A., Negrean V., Cojocaru C., Minescu B., Popa V., Blajan D., Nastase-Melicovici D., Fruntelata A., Barbulescu S., Lukinyh L., Akhunova S., Vishneva E., Semenova I., Nikolaev K. Y., Shaydyuk O., Nilk R., Shalnev V., Apartsin K., Goloshchekin B. M., Shpagina L., Khlevchuk T., Arkhipov M., Malygin A., Shvarts Y., Khaisheva L., Popov D., Kobalava Z., Lipchenko A., Shapovalova Y., Zrazhevsky K., Greshnova I., Maslova N., Karabenenko A., Shogenov Z., Budankova E., Barbarash O., Uspenskiy Y., Kosmacheva E., Berns S., Kostenko V., Zateyshchikov D., Vishnevsky A., Boldueva S., Podzolkov V., Sergeeva E., Grinshtein Y., Khrustalev O., Bugrova O., Repin A., Andreev D., Petrovic P., Boskovic Matic T., Apostolovic S., Lazic Z., Stankovic D., Stankovic A., Mitov V., Sofronic D., Kopitovic I., Zdravkovic V., Joksimovic Z., Lazovic N., Petrovic-Stanojevic N., Ilic A., Vujadinovic O., Pencic-Popovic B., Andjelkovic N., Sekularac N., Hinic S., Radjen G., Zivkovic A., Putnikovic B., Ivanov I., Babic R., Van Zyl L., Hobson B., Engelbrecht J., Mitha I., Siebert H., Jacobson B., Breedt J., Prozesky H., Ntsekhe M., Bayat J., Ellis G., Tarr G., Adler D., Van Dyk C., Ismail S. M., Spargo C. E., Abdool-Gaffar M., Saaiman J., Venter K., Lorente Aroca M. L., Fernandez Portales F., Pedrajas Navas J., Rodriguez Botaro A., Santa Cruz Siminiani A., Lopez Reyes R., Bisbe i Company J., Piedecausa Selfa M., Velasco Garrido J., Sobrino-Martinez J., Munoz Delgado G., Sala Llinas E., Blanco Coronado J., Almenar Bonet L., Vida Gutierrez M., Sanchez Lora F., Sanchez Martinez R., Calderon E. J., Villalta Blanch J., De la Hera Galarza J. M., Bustamante Ruiz A., Garcia-Fuster M. J., Ripoll Vera T., Alvarez-Sala Walter L., Todoli Parra J. A., Diaz Fernandez J., Bosa Ojeda F., Pellicer-Ciscar C., Jara Palomares L., Quiles Granado J., Trigo Bautista A., Ruiz Bustillo S., Ordi Ros J., Tolosa-Vilella C., Marin Ortuno F., Garcia Sanchez F., Barba Martin R., Segovia Cubero J., Cuervas-Mons Martinez V., Galan Montejano M., Lopez Meseguer M., Sener Comert S., Koksal N., Tertemiz K., Ernam D., Dursun A. B., Yildiz O., Rudenko L., Abrahamovych O., Goloborodko A., Holovchenko N., Kulyk A., Yagensky A., Batushkin V., Zolotaikina V., Kozyolkin O., Faynyk A., Maslovskyy V., Petrovskyy R., Koshlia V., Chopey I., Burmak I., Malynovsky Y., Voronkov L., Karpenko O., Dziublyk O., Godlevska O., Borovyk V., Bezrodna L., Serik S., Ovsyannikova N., Vynnychenko L., Kopytsya M., Rudkovskiy V., Grishyna O., Vyshnyvetskyy I., Prystupa L., Tseluyko V., Perepeliuk M., Koval O., Sychov O., Church A., Goudie A., Elliott M., Ferguson C., Welker J., Kao C. K., Bhagwat R., Serota H., Bozorgchami H., Nambiar R., Spilseth S., Bhagwath G., Syed F., Morrow L., Updegrove J., Bercz P., Kambo V., Henderson D., Wright P., Dang N., Nadar V., Jaffrani N., El-Shahawy M., Grossman C. H., Pearle J., Weinstein D., Galanis T. P., Gazmuri R., Kastelic R., Martinez R., Laman D., Macchiavelli A., Kmetzo J., Thurm C., Kayembe T., Chandrashekhar Y., Bassetti D., Jaoude P., Williams H., Dewhurst R., Naqvi S., Burr J., Rodriguez-Cintron W., Jeanfreau R., Kosinski E., Ndukwu I. M., Sotolongo C., Daboul N., Wilmer C., Simon P., Tak T., Rees C., Gupta N., Lerner R., Graffagnino C., Reed R. M., Alford C. 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P., Gazmuri R., Kastelic R., Martinez R., Laman D., Macchiavelli A., Kmetzo J., Thurm C., Kayembe T., Chandrashekhar Y., Bassetti D., Jaoude P., Williams H., Dewhurst R., Naqvi S., Burr J., Rodriguez-Cintron W., Jeanfreau R., Kosinski E., Ndukwu I. M., Sotolongo C., Daboul N., Wilmer C., Simon P., Tak T., Rees C., Gupta N., Lerner R., Graffagnino C., Reed R. M., Alford C. M., Mody F., Wellmon B., Hamroff G., Rajan R., and Kaatz S.

Abstract

BACKGROUND Patients who are hospitalized for medical illness remain at risk for venous thromboembolism after discharge, but the role of extended thromboprophylaxis in the treatment of such patients is a subject of controversy. METHODS In this randomized, double-blind trial, medically ill patients who were at increased risk for venous thromboembolism on the basis of a modified International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) score of 4 or higher (scores range from 0 to 10, with higher scores indicating a higher risk of venous thromboembolism) or a score of 2 or 3 plus a plasma d-dimer level of more than twice the upper limit of the normal range (defined according to local laboratory criteria) were assigned at hospital discharge to either once-daily rivaroxaban at a dose of 10 mg (with the dose adjusted for renal insufficiency) or placebo for 45 days. The primary efficacy outcome was a composite of symptomatic venous thromboembolism or death due to venous thromboembolism. The principal safety outcome was major bleeding. RESULTS Of the 12,024 patients who underwent randomization, 12,019 were included in the intention-to-treat analysis. The primary efficacy outcome occurred in 50 of 6007 patients (0.83%) who were given rivaroxaban and in 66 of 6012 patients (1.10%) who were given placebo (hazard ratio, 0.76; 95% confidence interval [CI], 0.52 to 1.09; P = 0.14). The prespecified secondary outcome of symptomatic nonfatal venous thromboembolism occurred in 0.18% of patients in the rivaroxaban group and 0.42% of patients in the placebo group (hazard ratio, 0.44; 95% CI, 0.22 to 0.89). Major bleeding occurred in 17 of 5982 patients (0.28%) in the rivaroxaban group and in 9 of 5980 patients (0.15%) in the placebo group (hazard ratio, 1.88; 95% CI, 0.84 to 4.23). CONCLUSIONS Rivaroxaban, given to medical patients for 45 days after hospital discharge, was not associated with a significantly lower risk of symptomatic venous thromboembolism and death

Published
2018

35. Urinary Leukotriene E4 and Prostaglandin D2 Metabolites Increase in Adult and Childhood Severe Asthma Characterized by Type 2 Inflammation. A Clinical Observational Study

Author

Kolmert, Johan, primary, Gómez, Cristina, additional, Balgoma, David, additional, Sjödin, Marcus, additional, Bood, Johan, additional, Konradsen, Jon R., additional, Ericsson, Magnus, additional, Thörngren, John-Olof, additional, James, Anna, additional, Mikus, Maria, additional, Sousa, Ana R., additional, Riley, John H., additional, Bates, Stewart, additional, Bakke, Per S., additional, Pandis, Ioannis, additional, Caruso, Massimo, additional, Chanez, Pascal, additional, Fowler, Stephen J., additional, Geiser, Thomas, additional, Howarth, Peter, additional, Horváth, Ildikó, additional, Krug, Norbert, additional, Montuschi, Paolo, additional, Sanak, Marek, additional, Behndig, Annelie, additional, Shaw, Dominick E., additional, Knowles, Richard G., additional, Holweg, Cécile T. J., additional, Wheelock, Åsa M., additional, Dahlén, Barbro, additional, Nordlund, Björn, additional, Alving, Kjell, additional, Hedlin, Gunilla, additional, Chung, Kian Fan, additional, Adcock, Ian M., additional, Sterk, Peter J., additional, Djukanovic, Ratko, additional, Dahlén, Sven-Erik, additional, Wheelock, Craig E., additional, Ahmed, H., additional, Auffray, C., additional, Bansal, A. T., additional, Bel, E. H., additional, Bigler, J., additional, Billing, B., additional, Baribaud, F., additional, Bisgaard, H., additional, Boedigheimer, M. J., additional, Bønnelykke, K., additional, Brandsma, J., additional, Brinkman, P., additional, Bucchioni, E., additional, Burg, D., additional, Bush, A., additional, Chaiboonchoe, A., additional, Compton, C. H., additional, Corfield, J., additional, Cunoosamy, D., additional, D’Amico, A., additional, De Meulder, B., additional, Erpenbeck, V. J., additional, Erzen, D., additional, Fichtner, K., additional, Fitch, N., additional, Fleming, L. J., additional, Formaggio, E., additional, Frey, U., additional, Gahlemann, M., additional, Goss, V., additional, Guo, Y., additional, Hashimoto, S., additional, Haughney, J., additional, Hekking, P. W., additional, Higenbottam, T., additional, Hohlfeld, J. M., additional, Knox, A. J., additional, Lazarinis, N., additional, Lefaudeux, D., additional, Loza, M. J., additional, Lutter, R., additional, Manta, A., additional, Masefield, S., additional, Matthews, J. G., additional, Mazein, A., additional, Meiser, A., additional, Middelveld, R. J. M., additional, Miralpeix, M., additional, Mores, N., additional, Murray, C. S., additional, Musial, J., additional, Myles, D., additional, Pahus, L., additional, Pavlidis, S., additional, Postle, A., additional, Powel, P., additional, Praticò, G., additional, PuigValls, M., additional, Rao, N., additional, Roberts, A., additional, Roberts, G., additional, Rowe, A., additional, Sandström, T., additional, Schofield, J. P. R., additional, Seibold, W., additional, Selby, A., additional, Sigmund, R., additional, Singer, F., additional, Skipp, P. J., additional, Smicker, M., additional, Sun, K., additional, Thornton, B., additional, Uddin, M., additional, van Aalderen, W. M., additional, van Geest, M., additional, Vestbo, J., additional, Vissing, N. H., additional, Wagener, A. H., additional, Wagers, S. S., additional, Weiszhart, Z., additional, Wilson, S. J., additional, and Östling, J., additional

Published
2021
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