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4. A deep learning approach predicting the activity of COVID-19 therapeutics and vaccines against emerging variants

Author

Robert P. Matson, Isin Y. Comba, Eli Silvert, Michiel J. M. Niesen, Karthik Murugadoss, Dhruti Patwardhan, Rohit Suratekar, Elizabeth-Grace Goel, Brittany J. Poelaert, Kanny K. Wan, Kyle R. Brimacombe, AJ Venkatakrishnan, and Venky Soundararajan

Subjects
Biology (General), QH301-705.5
Abstract

Abstract Understanding which viral variants evade neutralization is crucial for improving antibody-based treatments, especially with rapidly evolving viruses like SARS-CoV-2. Yet, conventional assays are labor intensive and cannot capture the full spectrum of variants. We present a deep learning approach to predict changes in neutralizing antibody activity of COVID-19 therapeutics and vaccine-elicited sera/plasma against emerging viral variants. Our approach leverages data of 67,885 unique SARS-CoV-2 Spike sequences and 7,069 in vitro assays. The resulting model accurately predicted fold changes in neutralizing activity (R2 = 0.77) for a test set (N = 980) of data collected up to eight months after the training data. Next, the model was used to predict changes in activity of current therapeutic and vaccine-induced antibodies against emerging SARS-CoV-2 lineages. Consistent with other work, we found significantly reduced activity against newer XBB descendants, notably EG.5, FL.1.5.1, and XBB.1.16; primarily attributed to the F456L spike mutation.

Published
2024
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6. Sex dependence of postoperative pulmonary complications – A post hoc unmatched and matched analysis of LAS VEGAS

Author

Kroell, Wolfgang, Metzler, Helfried, Struber, Gerd, Wegscheider, Thomas, Gombotz, Hans, Hiesmayr, Michael, Schmid, Werner, Urbanek, Bernhard, Kahn, David, Momeni, Mona, Pospiech, Audrey, Lois, Fernande, Forget, Patrice, Grosu, Irina, Poelaert, Jan, van Mossevelde, Veerle, van Malderen, Marie-Claire, Dylst, Dimitri, van Melkebeek, Jeroen, Beran, Maud, de Hert, Stefan, De Baerdemaeker, Luc, Heyse, Bjorn, Van Limmen, Jurgen, Wyffels, Piet, Jacobs, Tom, Roels, Nathalie, De Bruyne, Ann, van de Velde, Stijn, Leva, Brigitte, Damster, Sandrine, Plichon, Benoit, Juros-Zovko, Marina, Djonoviċ-Omanoviċ, Dejana, Pernar, Selma, Zunic, Josip, Miskovic, Petar, Zilic, Antonio, Kvolik, Slavica, Ivic, Dubravka, Azenic-Venzera, Darija, Skiljic, Sonja, Vinkovic, Hrvoje, Oputric, Ivana, Juricic, Kazimir, Frkovic, Vedran, Kopic, Jasminka, Mirkovic, Ivan, Karanovic, Nenad, Carev, Mladen, Dropulic, Natasa, Saric, Jadranka Pavicic, Erceg, Gorjana, Dvorscak, Matea Bogdanovic, Mazul-Sunko, Branka, Pavicic, Anna Marija, Goranovic, Tanja, Maldini, Branka, Radocaj, Tomislav, Gavranovic, Zeljka, Mladic-Batinica, Inga, Sehovic, Mirna, Stourac, Petr, Harazim, Hana, Smekalova, Olga, Kosinova, Martina, Kolacek, Tomas, Hudacek, Kamil, Drab, Michal, Brujevic, Jan, Vitkova, Katerina, Jirmanova, Katerina, Volfova, Ivana, Dzurnakova, Paula, Liskova, Katarina, Dudas, Radovan, Filipsky, Radek, el Kafrawy, Samir, Abdelwahab, Hisham Hosny, Metwally, Tarek, Abdel-Razek, Ahmed, El-Shaarawy, Ahmed Mostafa, Hasan, Wael Fathy, Ahmed, Ahmed Gouda, Yassin, Hany, Magdy, Mohamed, Abdelhady, Mahdy, Mahran, Mohamed, Herodes, Eiko, Kivik, Peeter, Oganjan, Juri, Aun, Annika, Sormus, Alar, Sarapuu, Kaili, Mall, Merilin, Karjagin, Juri, Futier, Emmanuel, Petit, Antoine, Gerard, Adeline, Marret, Emmanuel, Solier, Marc, Jaber, Samir, Prades, Albert, Krassler, Jens, Merzky, Simone, de Abreu, Marcel Gama, Uhlig, Christopher, Kiss, Thomas, Bundy, Anette, Bluth, Thomas, Gueldner, Andreas, Spieth, Peter, Scharffenberg, Martin, Thiem, Denny Tran, Koch, Thea, Treschan, Tanja, Schaefer, Maximilian, Bastin, Bea, Geib, Johann, Weiss, Martin, Kienbaum, Peter, Pannen, Benedikt, Gottschalk, Andre, Konrad, Mirja, Westerheide, Diana, Schwerdtfeger, Ben, Wrigge, Hermann, Simon, Philipp, Reske, Andreas, Nestler, Christian, Valsamidis, Dimitrios, Stroumpoulis, Konstantinos, Antholopoulos, Georgios, Andreou, Antonis, Karapanos, Dimitris, Theodoraki, Kassiani, Gkiokas, Georgios, Tasoulis, Marios-Konstantinos, Sidiropoulou, Tatiana, Zafeiropoulou, Foteini, Florou, Panagiota, Pandazi, Aggeliki, Tsaousi, Georgia, Nouris, Christos, Pourzitaki, Chryssa, Bystritski, Dmitri, Pizov, Reuven, Eden, Arieh, Pesce, Caterina Valeria, Campanile, Annamaria, Marrella, Antonella, Grasso, Salvatore, De Michele, Michele, Bona, Francesco, Giacoletto, Gianmarco, Sardo, Elena, Sottosanti, Luigi Giancarlo Vicari, Solca, Maurizio, Volta, Carlo Alberto, Spadaro, Savino, Verri, Marco, Ragazzi, Riccardo, Zoppellari, Roberto, Cinnella, Gilda, Raimondo, Pasquale, La Bella, Daniela, Mirabella, Lucia, D'antini, Davide, Pelosi, Paolo, Molin, Alexandre, Brunetti, Iole, Gratarola, Angelo, Pellerano, Giulia, Sileo, Rosanna, Pezzatto, Stefano, Montagnani, Luca, Pasin, Laura, Landoni, Giovanni, Zangrillo, Alberto, Beretta, Luigi, Di Parma, Ambra Licia, Tarzia, Valentina, Dossi, Roberto, Sassone, Marta Eugenia, Sances, Daniele, Tredici, Stefano, Spano, Gianluca, Castellani, Gianluca, Delunas, Luigi, Peradze, Sopio, Venturino, Marco, Arpino, Ines, Sher, Sara, Tommasino, Concezione, Rapido, Francesca, Morelli, Paola, Vargas, Maria, Servillo, Giuseppe, Cortegiani, Andrea, Raineri, Santi Maurizio, Montalto, Francesca, Russotto, Vincenzo, Giarratano, Antonino, Baciarello, Marco, Generali, Michela, Cerati, Giorgia, Leykin, Yigal, Bressan, Filippo, Bartolini, Vittoria, Zamidei, Lucia, Brazzi, Luca, Liperi, Corrado, Sales, Gabriele, Pistidda, Laura, Severgnini, Paolo, Brugnoni, Elisa, Musella, Giuseppe, Bacuzzi, Alessandro, Muhardri, Dalip, Gecaj-Gashi, Agreta, Sada, Fatos, Bytyqi, Adem, Karbonskiene, Aurika, Aukstakalniene, Ruta, Teberaite, Zivile, Salciute, Erika, Tikuisis, Renatas, Miliauskas, Povilas, Jurate, Sipylaite, Kontrimaviciute, Egle, Tomkute, Gabija, Xuereb, John, Bezzina, Maureen, Borg, Francis Joseph, Hemmes, Sabrine, Schultz, Marcus, Hollmann, Markus, Wiersma, Irene, Binnekade, Jan, Bos, Lieuwe, Nijbroek, Sunny, Boer, Christa, Duvekot, Anne, ’t Veld, Bas in, Werger, Alice, Dennesen, Paul, Severijns, Charlotte, De Jong, Jasper, Hering, Jens, van Beek, Rienk, Ivars, Stefan, Jammer, Ib, Breidablik, Alena, Hodt, Katharina Skirstad, Fjellanger, Frode, Avalos, Manuel Vico, Mellin-Olsen, Jannicke, Andersson, Elisabeth, Shafi-Kabiri, Amir, Molina, Ruby, Wutai, Stanley, Morais, Erick, Tareco, Glória, Ferreira, Daniel, Amaral, Joana, de Lurdes Goncalves Castro, Maria, Cadilha, Susana, Appleton, Sofia, Parente, Suzana, Correia, Mariana, Martins, Diogo, Monteirosa, Angela, Ricardo, Ana, Rodrigues, Sara, Horhota, Lucian, Grintescu, Ioana Marina, Mirea, Liliana, Grintescu, Ioana Cristina, Corneci, Dan, Negoita, Silvius, Dutu, Madalina, Garotescu, Ioana Popescu, Filipescu, Daniela, Prodan, Alexandru Bogdan, Droc, Gabriela, Fota, Ruxandra, Popescu, Mihai, Tomescu, Dana, Petcu, Ana Maria, Tudoroiu, Marian Irinel, Moise, Alida, Guran, Catalin-Traian, Gherghina, Iorel, Costea, Dan, Cindea, Iulia, Copotoiu, Sanda-Maria, Copotoiu, Ruxandra, Barsan, Victoria, Tolcser, Zsolt, Riciu, Magda, Moldovan, Septimiu Gheorghe, Veres, Mihaly, Gritsan, Alexey, Kapkan, Tatyana, Gritsan, Galina, Korolkov, Oleg, Kulikov, Alexander, Lubnin, Andrey, Ovezov, Alexey, Prokoshev, Pavel, Lugovoy, Alexander, Anipchenko, Natalia, Babayants, Andrey, Komissarova, Irina, Zalina, Karginova, Likhvantsev, Valery, Fedorov, Sergei, Lazukic, Aleksandra, Pejakovic, Jasmina, Mihajlovic, Dunja, Kusnierikova, Zuzana, Zelinkova, Maria, Bruncakova, Katarina, Polakovicova, Lenka, Sobona, Villiam, Novak-Supe, Barbka, Pekle-Golez, Ana, Jovanov, Miroljub, Strazisar, Branka, Markovic-Bozic, Jasmina, Novak-Jankovic, Vesna, Voje, Minca, Grynyuk, Andriy, Kostadinov, Ivan, Spindler-Vesel, Alenka, Moral, Victoria, Unzueta, Mari Carmen, Puigbo, Carlos, Fava, Josep, Canet, Jaume, Moret, Enrique, Nunez, Mónica Rodriguez, Sendra, Mar, Brunelli, Andrea, Rodenas, Frederic, Monedero, Pablo, Martinezv, Francisco Hidalgo, Temino, Maria Jose Yepes, Simon, Antonio Martínez, de Abajo Larriba, Ana, Lisi, Alberto, Perez, Gisela, Martinez, Raquel, Granell, Manuel, Vivo, Jose Tatay, Ruiz, Cristina Saiz, de Andrés Ibañez, Jose Antonio, Pastor, Ernesto, Soro, Marina, Ferrando, Carlos, Defez, Mario, Alvares-Santullano, Cesar Aldecoa, Perez, Rocio, Rico, Jesus, Jawad, Monir, Saeed, Yousif, Gillberg, Lars, Hedenstierma, Göran, Bengisun, Zuleyha Kazak, Kazbek, Baturay Kansu, Coskunfirat, Nesil, Boztug, Neval, Sanli, Suat, Yilmaz, Murat, Hadimioglu, Necmiye, Senturk, Nuzhet Mert, Camci, Emre, Kucukgoncu, Semra, Sungur, Zerrin, Sivrikoz, Nukhet, Ozgen, Serpil Ustalar, Toraman, Fevzi, Selvi, Onur, Senturk, Ozgur, Yildiz, Mine, Kuvaki, Bahar, Gunenc, Ferim, Kucukguclu, Semih, Ozbilgin, Şule, Maral, Jale, Canli, Seyda, Arun, Oguzhan, Saltali, Ali, Aydogan, Eyup, Akgun, Fatma Nur, Sanlikarip, Ceren, Karaman, Fatma Mine, Mazur, Andriy, Vorotyntsev, Sergiy, Rousseau, Guy, Barrett, Colin, Stancombe, Lucia, Shelley, Ben, Scholes, Helen, Limb, James, Rafi, Amir, Wayman, Lisa, Deane, Jill, Rogerson, David, Williams, John, Yates, Susan, Rogers, Elaine, Pulletz, Mark, Moreton, Sarah, Jones, Stephanie, Venkatesh, Suresh, Burton, Maudrian, Brown, Lucy, Goodall, Cait, Rucklidge, Matthew, Fuller, Debbie, Nadolski, Maria, Kusre, Sandeep, Lundberg, Michael, Everett, Lynn, Nutt, Helen, Zuleika, Maka, Carvalho, Peter, Clements, Deborah, Creagh-Brown, Ben, Watt, Philip, Raymode, Parizade, Pearse, Rupert, Mohr, Otto, Raj, Ashok, Creary, Thais, Chishti, Ahmed, Bell, Andrea, Higham, Charley, Cain, Alistair, Gibb, Sarah, Mowat, Stephen, Franklin, Danielle, West, Claire, Minto, Gary, Boyd, Nicholas, Mills, Gary, Calton, Emily, Walker, Rachel, Mackenzie, Felicity, Ellison, Branwen, Roberts, Helen, Chikungwa, Moses, Jackson, Clare, Donovan, Andrew, Foot, Jayne, Homan, Elizabeth, Montgomery, Jane, Portch, David, Mercer, Pauline, Palmer, Janet, Paddle, Jonathan, Fouracres, Anna, Datson, Amanda, Andrew, Alyson, Welch, Leanne, Rose, Alastair, Varma, Sandeep, Simeson, Karen, Rambhatla, Mrutyunjaya, Susarla, Jaysimha, Marri, Sudhakar, Kodaganallur, Krishnan, Das, Ashok, Algarsamy, Shivarajan, Colley, Julie, Davies, Simon, Szewczyk, Margaret, Smith, Thomas, Fernandez-Bustamante, Ana, Luzier, Elizabeth, Almagro, Angela, Melo, Marcos Vidal, Fernando, Luiz, Sulemanji, Demet, Sprung, Juraj, Weingarten, Toby, Kor, Daryl, Scavonetto, Federica, Tze, Yeo, Vermeulen, Tom D., Hol, Liselotte, Swart, Pien, Mills, Gary H., Putensen, Christian, Serpa Neto, Ary, Vidal Melo, Marcos F., Hollmann, Markus W., Gama de Abreu, Marcelo, Schultz, Marcus J., Hemmes, Sabrine N., and van Meenen, David M.

Published
2024
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12. Visualization of the Facial Nerve with Ultra-high–Frequency Ultrasound

Author

Jeroen Poelaert, MD, Renaat Coopman, MD, DDS, PhD, Matthias Ureel, MD, DDS, Nicolas Dhooghe, MD, Eva Genbrugge, MD, Tana Mwewa, MD, Phillip Blondeel, MD, PhD, and Hubert Vermeersch, MD, PhD

Subjects
Surgery, RD1-811
Abstract

Background:. Profound variations in facial nerve branching, combined with the severe impact of facial palsy on the patient’s quality of life, make surgery in this region challenging. Recent advancements in ultrasound (US) technology, including the improved visualization of small structures, have led to a sharp increase in its medical indications in various medical disciplines. We aimed to prove the feasibility of using ultra-high–frequency (UHF) US to visualize the facial nerve and to guide surgeons during surgery on and around the facial nerve. Methods:. A cadaveric study was performed on one hemi-face with a UHF US imaging system and state-of-the-art transducers. Firstly, a transcutaneous US was performed, and the facial nerve branches of interest (zygomatic, buccal, and marginal mandibular branches) were marked using US-guided color-injections of filler mixed with methylene blue. Skin and subcutaneous fat were then removed to simulate the intraoperative field. Secondly, an “intraoperative” US examination was performed, and the same branches were marked by US-guided color-injections of filler mixed with indocyanine green. Anterograde facial nerve dissection was performed, and the distance between the nerve branches and the injected filler was measured. Results:. All color-injections (mixed with both methylene blue and indocyanine green) were positioned right next to the nerve branches (

Published
2023
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16. Enterovirus D-68 Infection of Primary Rat Cortical Neurons: Entry, Replication, and Functional Consequences

Author

Katrien C. K. Poelaert, Regina G. D. M. van Kleef, Mengying Liu, Arno van Vliet, Heyrhyoung Lyoo, Lora-Sophie Gerber, Yoshiki Narimatsu, Christian Büll, Henrik Clausen, Erik de Vries, Remco H. S. Westerink, and Frank J. M. van Kuppeveld

Subjects
EV-D68, neurotropism, receptor, Microbiology, QR1-502
Abstract

ABSTRACT Enterovirus D68 (EV-D68) is an emerging pathogen associated with mild to severe respiratory disease. Since 2014, EV-D68 is also linked to acute flaccid myelitis (AFM), causing paralysis and muscle weakness in children. However, it remains unclear whether this is due to an increased pathogenicity of contemporary EV-D68 clades or increased awareness and detection of this virus. Here, we describe an infection model of primary rat cortical neurons to study the entry, replication, and functional consequences of different EV-D68 strains, including historical and contemporary strains. We demonstrate that sialic acids are important (co)receptors for infection of both neurons and respiratory epithelial cells. Using a collection of glycoengineered isogenic HEK293 cell lines, we show that sialic acids on either N-glycans or glycosphingolipids can be used for infection. Additionally, we show that both excitatory glutamatergic and inhibitory GABA-ergic neurons are susceptible and permissive to historical and contemporary EV-D68 strains. EV-D68 infection of neurons leads to the reorganization of the Golgi-endomembranes forming replication organelles, first in the soma and later in the processes. Finally, we demonstrate that the spontaneous neuronal activity of EV-D68-infected neuronal network cultured on microelectrode arrays (MEA) is decreased, independent of the virus strain. Collectively, our findings provide novel insights into neurotropism and -pathology of different EV-D68 strains, and argue that it is unlikely that increased neurotropism is a recently acquired phenotype of a specific genetic lineage. IMPORTANCE Acute flaccid myelitis (AFM) is a serious neurological illness characterized by muscle weakness and paralysis in children. Since 2014, outbreaks of AFM have emerged worldwide, and they appear to be caused by nonpolio enteroviruses, particularly enterovirus-D68 (EV-D68), an unusual enterovirus that is known to mainly cause respiratory disease. It is unknown whether these outbreaks reflect a change of EV-D68 pathogenicity or are due to increased detection and awareness of this virus in recent years. To gain more insight herein, it is crucial to define how historical and circulating EV-D68 strains infect and replicate in neurons and how they affect their physiology. This study compares the entry and replication in neurons and the functional consequences on the neural network upon infection with an old “historical” strain and contemporary “circulating” strains of EV-D68.

Published
2023
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18. COVID-19 and Cushing’s disease in a patient with ACTH-secreting pituitary carcinoma

Author

J M K de Filette, Bastiaan Sol, Gil Awada, Corina E Andreescu, David Unuane, Sandrine Aspeslagh, Jan Poelaert, and Bert Bravenboer

Subjects
Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

The pandemic caused by severe acute respiratory syndrome coronavirus 2 is of an unprecedented magnitude and has made it challenging to properly treat patients with urgent or rare endocrine disorders. Little is known about the risk of coronavirus disease 2019 (COVID-19) in patients with rare endocrine malignancies, such as pituitary carcinoma. We describe the case of a 43-year-old patient with adrenocorticotrophic hormone-secreting pituitary carcinoma who developed a severe COVID-19 infection. He had stabilized Cushing’s disease after multiple lines of treatment and was currently receiving maintenance immunotherapy with nivolumab (240 mg every 2 weeks) and steroidogenesis inhibition with ketoconazole (800 mg daily). On admission, he was urgently intubated for respiratory exhaustion. Supplementation of corticosteroid requirements consisted of high-dose dexamethasone, in analogy with the RECOVERY trial, followed by the reintroduction of ketoconazole under the coverage of a hydrocortisone stress regimen, which was continued at a dose depending on the current level of stress. He had a prolonged and complicated stay at the intensive care unit but was eventually discharged and able to continue his rehabilitation. The case points out that multiple risk factors for severe COVID-19 are present in patients with Cushing’s syndrome. ‘Block-replacement’ therapy with suppression of endogenous steroidogenesis and supplementation of corticosteroid requirements might be preferred in this patient population.

Published
2022
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19. The pathophysiological impact of intra-abdominal hypertension in pigs.

Author

Robert Wise, Reitze Rodseth, Ester Párraga-Ros, Rafael Latorre, Octavio López Albors, Laura Correa-Martín, Francisco M Sánchez-Margallo, Irma Eugenia Candanosa-Aranda, Jan Poelaert, Gregorio Castellanos, and Manu L N G Malbrain

Subjects
Medicine, Science
Abstract

BackgroundIntra-abdominal hypertension and abdominal compartment syndrome are common with clinically significant consequences. We investigated the pathophysiological effects of raised IAP as part of a more extensive exploratory animal study. The study design included both pneumoperitoneum and mechanical intestinal obstruction models.MethodsForty-nine female swine were divided into six groups: a control group (Cr; n = 5), three pneumoperitoneum groups with IAPs of 20mmHg (Pn20; n = 10), 30mmHg (Pn30; n = 10), 40mmHg (Pn40; n = 10), and two mechanical intestinal occlusion groups with IAPs of 20mmHg (MIO20; n = 9) and 30mmHg (MIO30; n = 5).ResultsThere were significant changes (pConclusionsThis study identified and quantified the impact of intra-abdominal hypertension at different pressures on several organ systems and highlighted the significance of even short-lived elevations. Two models of intra-abdominal pressure were used, with a mechanical obstruction model showing more rapid changes in metabolic and haematological changes. These may represent different underlying cellular and vascular pathophysiological processes, but this remains unclear.

Published
2023
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24. The Role of Cytoreductive Radical Prostatectomy in the Treatment of Newly Diagnosed Low-volume Metastatic Prostate Cancer. Results from the Local Treatment of Metastatic Prostate Cancer (LoMP) Registry

Author

Nicolaas Lumen, Elise De Bleser, Sarah Buelens, Wesley Verla, Filip Poelaert, Wietse Claeys, Valérie Fonteyne, Sofie Verbeke, Geert Villeirs, Kathia De Man, Sylvie Rottey, Charles Van Praet, Karel Decaestecker, and Piet Ost

Subjects
Prostate cancer, Metastasis, Radical prostatectomy, Prostate, Androgen deprivation therapy, Diseases of the genitourinary system. Urology, RC870-923, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background: Radiotherapy to the prostate (RTp) prolongs survival for patients with low-volume, newly diagnosed metastatic prostate cancer (ndmPC). Objective: to evaluate whether cytoreductive radical prostatectomy (cRP) is equally beneficial as RTp in low-volume ndmPC. Design, setting, and participants: A multicenter prospective registry was established in 2014 to observe patients with ndmPC. Eligible patients were offered cRP or RTp. For this study we selected only patients with low-volume ndmPC (n = 109). Of these, 48, 26, and 35 patients underwent cRP, RTp, and no local therapy (NLT), respectively. Median follow-up was 32 mo (interquartile range 16–49). Intervention: cRP was compared with RTp and NLT. Outcome measurements and statistical analysis: Overall survival (OS), cancer-specific survival (CSS), and local event–free survival (LEFS) were calculated using the Kaplan-Meier method. Factors prognostic for OS were identified using univariate and multivariate Cox regression analysis. Results and limitations: The 2-yr OS was 93%, 100%, and 69%, and 2-yr CSS was 93%, 100%, and 75% for cRP, RTp, and NLT, respectively. The cRP and RTp groups had better OS compared to NLT and there was no significant difference between cRP and RTp. The 2-yr LEFS was 92%, 77%, and 60% for cRP, RTp, and NLT, respectively. The cRP group had better LEFS compared to RTp and NLT, and there was no significant difference between RTp and NLT. Advanced tumor stage, Eastern Cooperative Oncology Group performance status ≥2, and NLT were negative prognostic factors for OS. The main limitation is selection of fitter patients with less advanced tumors for cRP and the small sample size. Conclusions: For selected patients with low-volume ndmPC, cRP is able to achieve similar OS and CSS to RTp. cRP is effective in preventing local events due to disease progression. Patient summary: Patients with a low volume of newly diagnosed prostate cancer that has spread beyond the prostate gland might benefit from removal of the prostate, which we found was as effective as radiotherapy to the prostate in prolonging survival. Removal of the prostate is effective in preventing urinary problems caused by cancer progression.

Published
2021
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32. Multi-organ point-of-care ultrasound for COVID-19 (PoCUS4COVID): international expert consensus

Author

Arif Hussain, Gabriele Via, Lawrence Melniker, Alberto Goffi, Guido Tavazzi, Luca Neri, Tomas Villen, Richard Hoppmann, Francesco Mojoli, Vicki Noble, Laurent Zieleskiewicz, Pablo Blanco, Irene W. Y. Ma, Mahathar Abd. Wahab, Abdulmohsen Alsaawi, Majid Al Salamah, Martin Balik, Diego Barca, Karim Bendjelid, Belaid Bouhemad, Pablo Bravo-Figueroa, Raoul Breitkreutz, Juan Calderon, Jim Connolly, Roberto Copetti, Francesco Corradi, Anthony J. Dean, André Denault, Deepak Govil, Carmela Graci, Young-Rock Ha, Laura Hurtado, Toru Kameda, Michael Lanspa, Christian B. Laursen, Francis Lee, Rachel Liu, Massimiliano Meineri, Miguel Montorfano, Peiman Nazerian, Bret P. Nelson, Aleksandar N. Neskovic, Ramon Nogue, Adi Osman, José Pazeli, Elmo Pereira-Junior, Tomislav Petrovic, Emanuele Pivetta, Jan Poelaert, Susanna Price, Gregor Prosen, Shalim Rodriguez, Philippe Rola, Colin Royse, Yale Tung Chen, Mike Wells, Adrian Wong, Wang Xiaoting, Wang Zhen, and Yaseen Arabi

Subjects
COVID-19, SARS-CoV-2, Point-of-care ultrasound (PoCUS), Focused cardiac ultrasound (FoCUS), Lung ultrasound (LUS), Echocardiography, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract COVID-19 has caused great devastation in the past year. Multi-organ point-of-care ultrasound (PoCUS) including lung ultrasound (LUS) and focused cardiac ultrasound (FoCUS) as a clinical adjunct has played a significant role in triaging, diagnosis and medical management of COVID-19 patients. The expert panel from 27 countries and 6 continents with considerable experience of direct application of PoCUS on COVID-19 patients presents evidence-based consensus using GRADE methodology for the quality of evidence and an expedited, modified-Delphi process for the strength of expert consensus. The use of ultrasound is suggested in many clinical situations related to respiratory, cardiovascular and thromboembolic aspects of COVID-19, comparing well with other imaging modalities. The limitations due to insufficient data are highlighted as opportunities for future research.

Published
2020
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33. Acceptance of mHealth among health professionals: a case study on anesthesia practitioners

Author

Hugo Carvalho, Michael Verdonck, Patrice Forget, and Jan Poelaert

Subjects
Anesthesia, mHealth, Smartphone application, Smartphone peripherals, Apps, Anesthesiology, RD78.3-87.3
Abstract

Abstract Background mHealth, the practice of medicine aided by mobile devices is a growing market. Although the offer on Anesthesia applications (Apps) is quite prolific, representative formal assessments on the views of anesthesia practitioners on its use and potential place in daily practice is lacking. This survey aimed thus to cross-assess the Belgian anesthesia population on the use of smartphone Apps and peripherals. Methods The survey was exclusively distributed as an online anonymous questionnaire. Sharing took place via hyperlink forwarding by the Belgian Society for Anesthesia and Reanimation (BSAR) and by the Belgian Association for Regional Anesthesia (BARA) to all registered members. The first answer took place on 5 September 2018, the last on 22 January 2019. Results Three hundred forty-nine answers were obtained (26.9% corresponding to trainees, 73.1% to specialists). Anesthesiologists were positively confident that Apps and peripherals could help improve anesthesia care (57.0 and 47.9%, respectively, scored 4 or 5, in a scale from 0 to 5). Trainees were significantly more confident than specialists on both mobile Apps (71.2% and 51.8%, respectively; p = 0.001) and peripherals (77.7% and 45.1%, respectively; p = 0.09). The usefulness of Apps and Peripherals was rated 1 or below (on a 0 to 5 scale), respectively, by 9.5 and 14.6% of the total surveyed population, being specialists proportionally less confident in Smartphone peripherals than trainees (p = 0.008). Mobile apps are actively used by a significantly higher proportional number of trainees (67.0% vs. 37.3%, respectively; p = 0.000001). The preferred category of mobile Apps was dose-calculating applications (39.15%), followed by digital books (21. 1%) and Apps for active perioperative monitoring (20.0%). Conclusions Belgian Anesthesia practitioners show a global positive attitude towards smartphone Apps and Peripherals, with trainees trending to be more confident than specialists. Trial registration ClinicalTrials.gov database Identifier: NCT03750084 . Retrospectively registered on 21 November 2018.

Published
2020
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34. The histone deacetylase inhibitor M344 as a multifaceted therapy for pancreatic cancer

Author

Shelby M. Knoche, Gabrielle L. Brumfield, Benjamin T. Goetz, Bailee H. Sliker, Alaina C. Larson, Madeline T. Olson, Brittany J. Poelaert, Audrey Bavari, Ying Yan, Jennifer D. Black, and Joyce C. Solheim

Subjects
Medicine, Science
Abstract

The histone deacetylase (HDAC) inhibitor vorinostat, used with gemcitabine and other therapies, has been effective in treatment of experimental models of pancreatic cancer. In this study, we demonstrated that M344, an HDAC inhibitor, is efficacious against pancreatic cancer in vitro and in vivo, alone or with gemcitabine. By 24 hours post-treatment, M344 augments the population of pancreatic cancer cells in G1, and at a later time point (48 hours) it increases apoptosis. M344 inhibits histone H3 deacetylation and slows pancreatic cancer cell proliferation better than vorinostat, and it does not decrease the viability of a non-malignant cell line more than vorinostat. M344 also elevates pancreatic cancer cell major histocompatibility complex (MHC) class I molecule expression, potentially increasing the susceptibility of pancreatic cancer cells to T cell lysis. Taken together, our findings support further investigation of M344 as a pancreatic cancer treatment.

Published
2022

35. Two-year follow-up of one-stage left unilateral thoracoscopic epicardial and transcatheter endocardial ablation for persistent and long-standing persistent atrial fibrillation

Author

de Asmundis, Carlo, Varnavas, Varnavas, Sieira, Juan, Ströker, Erwin, Coutiño, Henrique E., Terasawa, Muryo, Abugattas, Juan Pablo, Salghetti, Francesca, Maj, Riccardo, Guimarães, Osório Thiago, Iacopino, Saverio, Umbrain, Vincent, Poelaert, Jan, Brugada, Pedro, Gelsomino, Sandro, Chierchia, Gian-Battista, and La Meir, Mark

Published
2020
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37. Hybrid thoracoscopic epicardial ablation of right ventricular outflow tract in patients with Brugada syndrome

Author

Salghetti, Francesca, de Asmundis, Carlo, Sieira, Juan, Coutiño, Hugo Enrique, Abugattas, Juan Pablo, Varnavas, Varnavas, Maj, Riccardo, Terasawa, Muryo, Guimarães Osório, Thiago, Stroker, Erwin, Capulzini, Lucio, Iacopino, Saverio, Paparella, Gaetano, Umbrain, Vincent, Poelaert, Jan, Van Dooren, Sonia, Brugada, Pedro, Chierchia, Gian Battista, and La Meir, Mark

Published
2019
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38. Association between night-time surgery and occurrence of intraoperative adverse events and postoperative pulmonary complications

Author

Kroell, W., Metzler, H., Struber, G., Wegscheider, T., Gombotz, H., Hiesmayr, M., Schmid, W., Urbanek, B., Kahn, D., Momeni, M., Pospiech, A., Lois, F., Forget, P., Grosu, I., Poelaert, J., Mossevelde, V., van Malderen, M.C., Dylst, D., Melkebeek, J.V., Beran, M., Hert, S.D., Baerdemaeker, L.D., Heyse, B., Limmen, J.V., Wyffels, P., Jacobs, T., Roels, N., Bruyne, A.D., Velde, S.V.D., Marina, J.Z., Dejana, D.O., Pernar, S., Zunic, J., Miskovic, P., Zilic, A., Kvolik, S., Ivic, D., Darija, A.V., Skiljic, S., Vinkovic, H., Oputric, I., Juricic, K., Frkovic, V., Kopic, J., Mirkovic, I., Saric, J.P., Erceg, G., Dvorscak, M.B., Branka, M.S., Pavicic, A.M., Goranovic, T., Maldini, B., Radocaj, T., Gavranovic, Z., Inga, M.B., Sehovic, M., Stourac, P., Harazim, H., Smekalova, O., Kosinova, M., Kolacek, T., Hudacek, K., Drab, M., Brujevic, J., Vitkova, K., Jirmanova, K., Volfova, I., Dzurnakova, P., Liskova, K., Dudas, R., Filipsky, R., Kafrawy, S.E., Abdelwahab, H.H., Metwally, T., Ahmed, A.R., Ahmed Mostafa, E.S., Hasan, W.F., Ahmed, A.G., Yassin, H., Magdy, M., Abdelhady, M., Mahran, M., Herodes, E., Kivik, P., Oganjan, J., Aun, A., Sormus, A., Sarapuu, K., Mall, M., Karjagin, J., Futier, E., Petit, A., Gerard, A., Marret, E., Solier, M., Jaber, S., Prades, A., Krassler, J., Merzky, S., Abreu, M.G.D., Uhlig, C., Kiss, T., Bundy, A., Bluth, T., Gueldner, A., Spieth, P., Scharffenberg, M., Thiem, D.T., Koch, T., Treschan, T., Schaefer, M., Bastin, B., Geib, J., Weiss, M., Kienbaum, P., Pannen, B., Gottschalk, A., Konrad, M., Westerheide, D., Schwerdtfeger, B., Wrigge, H., Simon, P., Reske, A., Nestler, C., Valsamidis, D., Stroumpoulis, K., Antholopoulos, G., Andreou, A., Karapanos, D., Theodoraki, K., Gkiokas, G., Tasoulis, M.K., Sidiropoulou, T., Zafeiropoulou, F., Florou, P., Pandazi, A., Tsaousi, G., Nouris, C., Pourzitaki, C., Bystritski, D., Pizov, R., Eden, A., Pesce, C.V., Campanile, A., Marrella, A., Grasso, S., Michele, M.D., Bona, F., Giacoletto, G., Sardo, E., Sottosanti, L.G.V., Solca, M., Volta, C.A., Spadaro, S., Verri, M., Ragazzi, R., Zoppellari, R., Cinnella, G., Raimondo, P., Bella, D.L., Mirabella, L., D'antini, D., Pelosi, P., Molin, A., Brunetti, I., Gratarola, A., Pellerano, G., Sileo, R., Pezzatto, S., Montagnani, L., Pasin, L., Landoni, G., Zangrillo, A., Beretta, L., Parma, A.L.D., Tarzia, V., Dossi, R., Sassone, M.E., Sances, D., Tredici, S., Spano, G., Castellani, G., Delunas, L., Peradze, S., Venturino, M., Arpino, I., Sher, S., Tommasino, C., Rapido, F., Morelli, P., Vargas, M., Servillo, G., Cortegiani, A., Raineri, S.M., Montalto, F., Russotto, V., Giarratano, A., Baciarello, M., Generali, M., Cerati, G., Leykin, Y., Bressan, F., Bartolini, V., Zamidei, L., Brazzi, L., Liperi, C., Sales, G., Pistidda, L., Severgnini, P., Brugnoni, E., Musella, G., Bacuzzi, A., Muhardri, D., Agreta, G.G., Sada, F., Bytyqi, A., Karbonskiene, A., Aukstakalniene, R., Teberaite, Z., Salciute, E., Tikuisis, R., Miliauskas, P., Jurate, S., Kontrimaviciute, E., Tomkute, G., Xuereb, J., Bezzina, M., Borg, F. Joseph, Hemmes, S., Schultz, M., Hollmann, M., Wiersma, I., Binnekade, J., Bos, L., Boer, C., Duvekot, A., Veld, B.I ‘t, Werger, A., Dennesen, P., Severijns, C., Jong, J.D., Hering, J., Beek, R.V., Ivars, S., Jammer, I.B., Breidablik, A., Hodt, K.S., Fjellanger, F., Avalos, M.V., Jannicke, M.O., Andersson, E., Amir, S.K., Molina, R., Wutai, S., Morais, E., Tareco, G., Ferreira, D., Amaral, J., Castro, M.D.L.G., Cadilha, S., Appleton, S., Parente, S., Correia, M., Martins, D., Monteirosa, A., Ricardo, A., Rodrigues, S., Horhota, L., Grintescu, I.M., Mirea, L., Grintescu, I.C., Corneci, D., Negoita, S., Dutu, M., Popescu Garotescu, I., Filipescu, D., Prodan, A.B., Droc, G., Fota, R., Popescu, M., Tomescu, D., Petcu, A.M., Tudoroiu, M.I., Moise, A., Guran, C.T., Gherghina, I., Costea, D., Cindea, I., Copotoiu, S.M., Copotoiu, R., Barsan, V., Tolcser, Z., Riciu, M., Moldovan, S.G., Veres, M., Gritsan, A., Kapkan, T., Gritsan, G., Korolkov, O., Kulikov, A., Lubnin, A., Ovezov, A., Prokoshev, P., Lugovoy, A., Anipchenko, N., Babayants, A., Komissarova, I., Zalina, K., Likhvantsev, V., Fedorov, S., Lazukic, A., Pejakovic, J., Mihajlovic, D., Kusnierikova, Z., Zelinkova, M., Bruncakova, K., Polakovicova, L., Sobona, V., Barbka, N.S., Ana, P.G., Jovanov, M., Strazisar, B., Jasmina, M.B., Vesna, N.J., Voje, M., Grynyuk, A., Kostadinov, I., Alenka, S.V., Moral, V., Unzueta, M.C., Puigbo, C., Fava, J., Canet, J., Moret, E., Nunez, M.R., Sendra, M., Brunelli, A., Rodenas, F., Monedero, P., Hidalgo, F., Yepes, M.J., Martinez-Simon, A., Abajo, A., Lisi, A., Perez, G., Martinez, R., Granell, M., Vivo, J.T., Ruiz, C.S., Andrés Ibañez, J.A.D., Pastor, E., Soro, M., Ferrando, C., Defez, M., Cesar Aldecoa, A.S., Perez, R., Rico, J., Jawad, M., Saeed, Y., Gillberg, L., Bengisun, Z.K., Kazbek, B.K., Coskunfirat, N., Boztug, N., Sanli, S., Yilmaz, M., Hadimioglu, N., Senturk, N.M., Camci, E., Kucukgoncu, S., Sungur, Z., Sivrikoz, N., Ozgen, S.U., Toraman, F., Selvi, O., Senturk, O., Yildiz, M., Kuvaki, B., Gunenc, F., Kucukguclu, S., Ozbilgin, S., Maral, J., Canli, S., Arun, O., Saltali, A., Aydogan, E., Akgun, F.N., Sanlikarip, C., Karaman, F.M., Mazur, A., Vorotyntsev, S., Rousseau, G., Barrett, C., Stancombe, L., Shelley, B., Scholes, H., Limb, J., Rafi, A., Wayman, L., Deane, J., Rogerson, D., Williams, J., Yates, S., Rogers, E., Pulletz, M., Moreton, S., Jones, S., Venkatesh, S., Burton, M., Brown, L., Goodall, C., Rucklidge, M., Fuller, D., Nadolski, M., Kusre, S., Lundberg, M., Everett, L., Nutt, H., Zuleika, M., Carvalho, P., Clements, D., Ben, C.B., Watt, P., Raymode, P., Pearse, R., Mohr, O., Raj, A., Creary, T., Chishti, A., Bell, A., Higham, C., Cain, A., Gibb, S., Mowat, S., Franklin, D., West, C., Minto, G., Boyd, N., Mills, G., Calton, E., Walker, R., Mackenzie, F., Ellison, B., Roberts, H., Chikungwa, M., Jackson, C., Donovan, A., Foot, J., Homan, E., Montgomery, J., Portch, D., Mercer, P., Palmer, J., Paddle, J., Fouracres, A., Datson, A., Andrew, A., Welch, L., Rose, A., Varma, S., Simeson, K., Rambhatla, M., Susarla, J., Marri, S., Kodaganallur, K., Das, A., Algarsamy, S., Colley, J., Davies, S., Szewczyk, M., Smith, T., Ana, F.B., Luzier, E., Almagro, A., Melo, M.V., Fernando, L., Sulemanji, D., Sprung, J., Weingarten, T., Kor, D., Scavonetto, F., Tze, Y., Gregoretti, C., Neto, A.S., Hemmes, S.N.T., Ball, L., Hollmann, M.W., Mills, G.H., Melo, M.F.V., Putensen, C., Gama de Abreu, M., and Schultz, M.J.

Published
2019
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40. Surface Area and Curvature of the general Ellipsoid

Author

Poelaert, Daniel, Schniewind, Joachim, and Janssens, Frank

Subjects
Mathematics - Classical Analysis and ODEs
Abstract

This paper gives a detailed derivation of the surface of a tri-axial ellipsoid. The general result is in terms of the elliptic integrals of the first and second kind. It is in checked for all special cases included and the corresponding simplified formulae are given. Next, expressions for the mean and Gaussian curvature are derived. These curvatures depend only on: a) the three axes, and from the point under consideration, b) its distance to the centre and c) the length of the perpendicular from centre to the tangent plane of that point. Finally, it is noticed that at the four umbilic points of an ellipsoid, where the cicular sections degenerate to a point, the two principal curvatures are equal and have the simple expression (a c / b^3)where a>b>c are the half-axes., Comment: 12 pages, 3 figures

Published
2011

44. Contemporary perioperative haemodynamic monitoring

Author

Qianyun Pang, Jan Hendrickx, Hong-Liang Liu, and Jan Poelaert

Subjects
haemodynamics, monitoring, noninvasive, Anesthesiology, RD78.3-87.3, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Haemodynamic monitoring is the cornerstone in the optimization of tissue perfusion and the prevention of deteriorating metabolism. Haemodynamic alterations could be summarized in terms of cardiac dysfunction, changes of loading conditions (preload or/and afterload), and patient related issues. This review aims to present the clinical applications of different haemodynamic monitoring techniques, discuss advantages and disadvantages, and provide guidance to help the clinician select those techniques suitable to optimize haemodynamics in individual patients during the perioperative period.

Published
2019
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45. Unravelling the first key steps in equine herpesvirus type 5 (EHV5) pathogenesis using ex vivo and in vitro equine models

Author

Jolien Van Cleemput, Katrien C. K. Poelaert, Kathlyn Laval, and Hans J. Nauwynck

Subjects
Veterinary medicine, SF600-1100
Abstract

Abstract Equine herpesvirus type 5 (EHV5) is a ubiquitous, yet obscure pathogen in the horse population and is commonly associated with fatal equine multinodular pulmonary fibrosis (EMPF). To date, little is known about the precise pathogenesis of EHV5. Here, we evaluated the dynamics of EHV5 infection in representative ex vivo and in vitro equine models, using immunofluorescence staining and virus titration. EHV5 was unable to infect epithelial cells lining the mucosa of nasal and tracheal explants. Similarly, primary equine respiratory epithelial cells (EREC) were not susceptible to EHV5 following inoculation at the apical or basolateral surfaces. Upon direct delivery of EHV5 particles to lung explants, few EHV5-positive cell clusters were observed at 72 hours post-inoculation (hpi). These EHV5-positive cells were identified as cytokeratin-positive alveolar cells. Next, we examined the potential of EHV5 to infect three distinct equine PBMC populations (CD172a+ monocytes, CD3+ T lymphocytes and Ig light chain+ B lymphocytes). Monocytes did not support EHV5 replication. In contrast, up to 10% of inoculated equine T and B lymphocytes synthetized intracellular viral antigens 24 hpi and 72 hpi, respectively. Still, the production of mature virus particles was hampered, as we did not observe an increase in extracellular virus titer. After reaching a peak, the percentage of infected T and B lymphocytes decayed, which was partly due to the onset of apoptosis, but not necrosis. Based on these findings, we propose a model for EHV5 pathogenesis in the horse. Uncovering EHV5 pathogenesis is the corner step to finally contain or even eradicate the virus.

Published
2019
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46. Exploratory Outlier Detection for Acceleromyographic Neuromuscular Monitoring: Machine Learning Approach

Author

Michaël Verdonck, Hugo Carvalho, Johan Berghmans, Patrice Forget, and Jan Poelaert

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Public aspects of medicine, RA1-1270
Abstract

BackgroundBecause of their kinetic nature, artifactual recordings of acceleromyography-based neuromuscular monitoring devices are not unusual. These generate a great deal of cynicism among anesthesiologists, constituting an obstacle toward their widespread adoption. Through outlier analysis techniques, monitoring devices can learn to detect and flag signal abnormalities. ObjectiveThis study aims to engineer a set of features that enable the detection of outliers in the form of erroneous train-of-four (TOF) measurements from an acceleromyographic-based device. These features are tested for their potential in the detection of erroneous TOF measurements by developing an outlier detection algorithm. MethodsA data set encompassing 533 high-sensitivity TOF measurements from 35 patients was created based on a multicentric open label trial of a purpose-built accelero- and gyroscopic-based neuromuscular monitoring app. A basic set of features was extracted based on raw data while a second set of features was purpose engineered based on TOF pattern characteristics. Two cost-sensitive logistic regression (CSLR) models were deployed to evaluate the performance of these features. The final output of the developed models was a binary classification, indicating if a TOF measurement was an outlier or not. ResultsA total of 7 basic features were extracted based on raw data, while another 8 features were engineered based on TOF pattern characteristics. The model training and testing were based on separate data sets: one with 319 measurements (18 outliers) and a second with 214 measurements (12 outliers). The F1 score (95% CI) was 0.86 (0.48-0.97) for the CSLR model with engineered features, significantly larger than the CSLR model with the basic features (0.29 [0.17-0.53]; P

Published
2021
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47. Noncanonical Transmission of a Measles Virus Vaccine Strain from Neurons to Astrocytes

Author

Katrien C. K. Poelaert, Riley M. Williams, Christine M. Matullo, and Glenn F. Rall

Subjects
Microbiology, QR1-502
Abstract

Viruses are the most important cause of infectious encephalitis in mammals worldwide; several thousand people, primarily the very young and the elderly, are impacted annually, and few therapies are reliably successful once neuroinvasion has occurred. To understand how viruses contribute to neuropathology, and to develop tools to prevent or ameliorate such infections, it is crucial to define if and how viruses disseminate among the different cell populations within the highly complex central nervous system.

Published
2021
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