Citations 2
Immune checkpoint dysregulation in COVID-19 pathogenesis and disease severity.
Villalba, Julian A. , Shih, Angela , Alba, George A. , Loyola-Rodríguez, Georgina, Alcántara, Ismael Ramírez, Ferreira, Luíz Carlos de Lima , Stigliano, Egidio, Hirschbühl, Klaus , Argueta, Allan , Ackermann, Maximillian , Werlein, Christopher , Uribe‐Uribe, Norma , Vázquez-Benítez, Greissy, Tzankov, Alexandar , Stalder, Anna K. , Francesqui, Joel , Osborn, Michael , Hanley, Brian , Johnston, Robert, Lacy, J. Matthew , Marshall, Desiree A. , Schwensen, Hanna Ferløv , Okudela, Koji , Flikweert, Antine, Iles, Linda , d’Amati, Giulia , Träger, Lene Hoffmann , Çınar, Hüseyin, Aguiar, Diego , Dolhnokoff, Marisa, Chilosi, Marco , Salmon, I, Colville‐Ebeling, Bonnie, Poissy, Julien , Haahr, Martha Kirstine , Reyes, Fabiola, Parry, Blair A. , Garlin, Michelle, Hilburn, Caroline F., ELLIOTT, G. A., Rosas, Iván O. , Sade-Feldman, Moshe , Hacohen, Nir , Baden, Lindsey R. , Li, Jonathan Z. , Schaller, Tina , Gigli, L, Macciò, Umberto , Yick, David C.Y., Bruni, Barbara, Pernazza, Angelina , Mauad, Thaís , Dubini, Alessandra, Hartmann, Arndt, Remmelink, Myriam , Aviles, Alexis J., Barth, Jamie L., Boyraz, Bariş , Araujo-Medina, Milagros, Mendez-Pena, Javier E., Chebib, Ivan , Hung, Yin P. , Rosales, Ivy A. , Smith, Rex-Neal, Hung, Yin P , Tzankov, Alexandar , Li, Yijia , Poli, Sergio , Kunitoki, Keiko , Mehta, Arnav , Santana, Monique Freire , Lacerda, Marcus , Dell’Aquila, Marco , Arena, Vincenzo , Calabrese, Fiorella , Pezzuto, Federica , Märkl, Bruno , Lozano, Maria, Jonigk, Danny David , Pomara, Cristoforo , Salerno, Monica , Salas, Clara , Martínez, Daniel, Parra-Medina, Rafael Santiago , Bradley, Benjamin T. , Chen, Sonja , Varga, Zsuzsanna , Steinestel, Konrad , Harper, Holly , Aiolfi, Alberto , Scendoni, Roberto , Fabro, Alexandre Todorovic , Doglioni, Claudio , Rossi, Giulio , Poletti, Venerino , Herrmann, Martin , Pugh, Matthew , Yan, Lei , Gentili, Matteo , Garlin, Michelle A., Lo, Ying‐Chun , Elliott, Grant, Martínez, Leonardo , Stone, James R. , Colvin, Robert B. , Goldberg, Marcia B. , Filbin, Michael R. , Mino-Kenudson, Mari A. , Kröncke, Thomas J. , Gigli, Laura Álvarez, Sessa, Francesco , Caltabiano, Rosario , Menter, Thomas , Sellarés, Jacobo , Storgaard, Merete , Hamilton‐Dutoit, Stephen , Dannheim, Katelyn , Witte, Hanno Maximilian , Bona, Davide , Leth, Peter Mygind , Banner, Jytte , Batah, Sabrina Setembre , Silva, Luiz Fernando Ferraz da , Duarte‐Neto, Amaro Nunes , Saldiva, Paulo Hilário Nascimento , Munoz, Luis Enrique , Jensen, T. , Brøchner, Christian Beltoft , Gibier, Jean‐Baptiste , Gilbert, Andrea , Madrigal, Emilio , Ly, Amy , Hariri, Lida P. , Caldwell, Nicholas J
No container title available | October 2, 2024 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Accumulating evidence suggests dysregulated immune checkpoint (IC) signaling can exacerbate COVID-19 severity, but the role of these molecules in the pathogenesis of fatal COVID-19-related diffuse alveolar damage (DAD) remains elusive. Understanding how IC proteins influence acute lung injury due to COVID-19 can provide insights into potential therapeutic strategies to modulate immune responses and improve patient outcomes. Here, in a single-center autopsy cohort, we determined the cellular localization of ICs in lung tissue from cases of fatal COVID-19, DAD-comparators, and non-fibrotic controls by using immunohistochemistry, and investigated their association with clinical outcomes. We expanded our findings by performing analyses of publicly available single-cell RNA sequencing datasets from patients with fatal COVID-19 and non-fibrotic controls. We demonstrated the presence of protein-protein interaction networks of ICs in the lung cellular niche by performing transcriptomic profiling of lung tissue-derived RNA counts from patients with fatal COVID-19. Further, we leveraged data from the largest international, multi-center COVID-19 autopsy cohort and validated that, among patients with fatal COVID-19, those with higher PD-L1/CD274 expression in lung endothelial cells had more rapid clinical deterioration. Lastly, in a cohort of individuals with early COVID-19, IC plasma protein levels were elevated in those with persistent SARS-CoV-2 RNAemia and adverse clinical outcomes. Collectively, our data provide unique pathological insights into the role of IC dysregulation and differential disease severity in COVID-19.
Clinical implications of elective replacement indicator setting changes in patients with dual‐chamber pacemaker devices
Phillips, Kari A. , Ponamgi, Shiva , Mundell, Benjamin F. , Krushelnytskyy, Mykhaylo , Li, Zhuo , Rea, Robert F., Deshmukh, Abhishek , Espinosa, Raúl E. , Osborn, Michael J., Friedman, Paul A. , Mulpuru, Siva K. , Cha, Yong‐Mei , Neutzling, Lori B., Munger, Thomas M. , Kancharla, Krishna , Asirvatham, Samuel J. , Mundell, Benjamin, Rea, Robert, Osborn, Michael , Friedman, Paul A , Mulpuru, Siva K , Cha, Yong-Mei , Munger, Thomas, Asirvatham, Samuel J , McLeod, Christopher J.
Journal of Cardiovascular Electrophysiology | July 16, 2020 | Volume: 31 | Issue: 10 | Pages: 2704-2710
AbstractObjectiveThis study sought to determine if single‐chamber operation and/or loss of rate response (RR) during elective replacement indicator (ERI) in patients with dual‐chamber pacemakers lead to increased symptom burden, healthcare utilization, and atrial fibrillation (AF).BackgroundDual‐chamber pacemakers often change from dual‐ to single‐chamber pacing mode and/or lose RR functionality at ERI to preserve battery. Single‐chamber pacing increases the incidence of heart failure, AF, and pacemaker syndrome suggesting these changes may be deleterious.MethodsA retrospective analysis of 700 patients was completed. Three comparisons were analyzed: Comparison 1: mode change and RR loss versus no change; Comparison 2: RR loss only versus no change; Comparison 3: mode change only versus no change (in patients with no RR programmed at baseline).ResultsIn Comparison 1, 121 (46%) patients with setting changes experienced symptoms (most often dyspnea and fatigue/exercise intolerance) versus 3 (4%) without setting changes (p < .0001). Similar results were noted in Comparisons 2 and 3 (p = .0016 and p = .0001, respectively). In Comparison 1, patients with setting change sought provider contact more than patients without setting changes (p = .0001). A significant difference was not noted in Comparison 2 or 3. Overall 14 (2%) patients were hospitalized, all of whom had setting changes.ConclusionsSetting changes at ERI including a change from dual‐ to single‐chamber pacing and/or loss of RR results in a significantly increased symptom burden and increased healthcare utilization.