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202 results on '"Hoth, P."'

1. Eliminating the benzos: A benzodiazepine-sparing approach to preventing and treating alcohol withdrawal syndrome

Author

McCullough, Mary Alyce, Miller, Preston R., Martin, Tamriage, Rebo, Kristin A., Stettler, Gregory R., Martin, Robert Shayn, Cantley, Morgan, Shilling, Elizabeth H., Hoth, James J., and Nunn, Andrew M.

Abstract

Implementation of a benzodiazepine sparing protocol to both prevent and treat alcohol withdrawal syndrome in trauma patients is safe, reduces withdrawal and decreases the need for benzodiazepines. @AtriumHealth @WakeACS @nunndre @MAMcCullough #AAST2023.

Published
2024
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2. Sicherheitsaspekte und Vorbereitung zur Notfallvorsorge und Gefahrenabwehr in Kliniken bei MANV/TerrorMANV

Author

Hoth, Patrick, Bieler, Dan, Friemert, Benedikt, Franke, Axel, Blätzinger, Markus, and Achatz, Gerhard

Abstract

Hintergrund: Weltweite terroristische Aktivitäten seit „9/11“ und folgend auch im europäischen Raum haben im Rahmen der Bewertung von kritischer Infrastruktur in Deutschland zu einem Umdenken auch hinsichtlich der Sicherheit an und in Kliniken geführt. Ziel der Arbeit: Die vorliegende Publikation befasst sich mit der Bewertung vorliegender Konzepte zu Themen wie „Alarmierung“, „Sicherheit“, „Kommunikation“ und „Vorbereitung“ im vorgenannten Kontext. Material und Methoden: Anhand einer Literatursichtung sowie einer Umfrage unter den Teilnehmern*innen der 3. Notfallkonferenz der DGU (Deutsche Gesellschaft für Unfallchirurgie) werden diese Thematik und die aktuell vorliegende Situation weiter analysiert und vorgestellt. Ergebnisse: Die gewonnenen Daten verdeutlichen, dass ein Großteil der Kliniken zwar über eine Krankenhausalarm- und Einsatzplanung verfügt, jedoch die Frequenz der Aktualisierungen und die innerklinische Kommunikation zur Steigerung der Wahrnehmung eine deutliche Streuung zeigen. Diskussion: Zusammenfassend scheint die latente Bedrohung durch terroristische Aktivitäten dazu geführt zu haben, dass sich deutsche Kliniken in der Bewertung als kritische Infrastruktur mit der Thematik „Krankenhausalarm- und Einsatzplanung“ auseinandergesetzt und diese überwiegend auch umgesetzt haben. Allerdings zeigt sich für die nachgeordneten Bereiche und die aus der Alarmplanung ableitbaren Konsequenzen noch nicht die nötige Stringenz, um letztendlich adäquate Reaktionen in diesen besonderen Szenarien im Hinblick auf die Sicherheit in und an deutschen Kliniken zu gewährleisten.

Published
2024
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3. Clinical Markers Associated With Risk of Suicide or Drug Overdose Among Individuals With Smoking Exposure

Author

Adviento, Brigid A., Regan, Elizabeth A., Make, Barry J., Han, MeiLan K., Foreman, Marilyn G., Iyer, Anand S., Bhatt, Surya P., Kim, Victor, Bon, Jessica, Soler, Xavier, Kinney, Gregory L., Hanania, Nicola A., Lowe, Katherine E., Holm, Kristen E., Yohannes, Abebaw M., Shinozaki, Gen, Hoth, Karin F., Fiedorowicz, Jess G., Crapo, James D., Silverman, Edwin K., Make, Barry J., Regan, Elizabeth A., Beaty, Terri H., Castaldi, Peter J., Cho, Michael H., DeMeo, Dawn L., El Boueiz, Adel, Foreman, Marilyn G., Ghosh, Auyon, Hayden, Lystra P., Hersh, Craig P., Hetmanski, Jacqueline, Hobbs, Brian D., Hokanson, John E., Kim, Wonji, Laird, Nan, Lange, Christoph, Lutz, Sharon M., McDonald, Merry-Lynn, Prokopenko, Dmitry, Moll, Matthew, Morrow, Jarrett, Qiao, Dandi, Regan, Elizabeth A., Saferali, Aabida, Sakornsakolpat, Phuwanat, Silverman, Edwin K., Wan, Emily S., Yun, Jeong, Centeno, Juan Pablo, Charbonnier, Jean-Paul, Coxson, Harvey O., Galban, Craig J., Han, MeiLan K., Hoffman, Eric A., Humphries, Stephen, Jacobson, Francine L., Judy, Philip F., Kazerooni, Ella A., Kluiber, Alex, Lynch, David A., Nardelli, Pietro, Newell, John D., Notary, Aleena, Oh, Andrea, Regan, Elizabeth A., Ross, James C., San Jose Estepar, Raul, Schroeder, Joyce, Sieren, Jered, Stoel, Berend C., Tschirren, Juerg, Van Beek, Edwin, van Ginneken, Bram, van Rikxoort, Eva, Sanchez-Ferrero, Gonzalo Vegas, Veitel, Lucas, Washko, George R., Wilson, Carla G., Jensen, Robert, Strand, Matthew, Crooks, Jim, Pratte, Katherine, Khatiwada, Aastha, Wilson, Carla G., Hokanson, John E., Austin, Erin, Kinney, Gregory, Lutz, Sharon M., Young, Kendra A., Bhatt, Surya P., Bon, Jessica, Diaz, Alejandro A., Han, MeiLan K., Make, Barry, Murray, Susan, Regan, Elizabeth, Soler, Xavier, Wilson, Carla G., Bowler, Russell P., Kechris, Katerina, Banaei-Kashani, Farnoush, Curtis, Jeffrey L., Pernicano, Perry G., Hanania, Nicola, Atik, Mustafa, Boriek, Aladin, Guntupalli, Kalpatha, Guy, Elizabeth, Parulekar, Amit, DeMeo, Dawn L., Hersh, Craig, Jacobson, Francine L., Washko, George, Barr, R. Graham, Austin, John, D’Souza, Belinda, Thomashow, Byron, MacIntyre, Neil, McAdams, H. Page, Washington, Lacey, McEvoy, Charlene, Tashjian, Joseph, Wise, Robert, Brown, Robert, Hansel, Nadia N., Horton, Karen, Lambert, Allison, Putcha, Nirupama, Casaburi, Richard, Adami, Alessandra, Budoff, Matthew, Fischer, Hans, Porszasz, Janos, Rossiter, Harry, Stringer, William, Sharafkhaneh, Amir, Lan, Charlie, Wendt, Christine, Bell, Brian, Kunisaki, Ken M., Flenaugh, Eric L., Gebrekristos, Hirut, Ponce, Mario, Terpenning, Silanath, Westney, Gloria, Bowler, Russell, Lynch, David A., Rosiello, Richard, Pace, David, Criner, Gerard, Ciccolella, David, Cordova, Francis, Dass, Chandra, D’Alonzo, Gilbert, Desai, Parag, Jacobs, Michael, Kelsen, Steven, Kim, Victor, Mamary, A. James, Marchetti, Nathaniel, Satti, Aditi, Shenoy, Kartik, Steiner, Robert M., Swift, Alex, Swift, Irene, Vega-Sanchez, Maria Elena, Dransfield, Mark, Bailey, William, Bhatt, Surya P., Iyer, Anand, Nath, Hrudaya, Wells, J. Michael, Conrad, Douglas, Soler, Xavier, Yen, Andrew, Comellas, Alejandro P., Hoth, Karin F., Newell, John, Thompson, Brad, Han, MeiLan K., Kazerooni, Ella, Labaki, Wassim, Galban, Craig, Vummidi, Dharshan, Billings, Joanne, Begnaud, Abbie, Allen, Tadashi, Sciurba, Frank, Bon, Jessica, Chandra, Divay, Weissfeld, Joel, Anzueto, Antonio, Adams, Sandra, Maselli-Caceres, Diego, Ruiz, Mario E., and Singh, Harjinder

Abstract

Studies have shown that COPD and smoking are associated with increased suicide risk. To date, there are no prospective studies examining suicide risk among individuals with smoking exposure along a spectrum of pulmonary diseases ranging from normal spirometry to severe COPD.

Published
2023
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4. Association of Mitochondrial DNA Copy Number With Brain MRI Markers and Cognitive Function

Author

Zhang, Yuankai, Liu, Xue, Wiggins, Kerri L., Kurniansyah, Nuzulul, Guo, Xiuqing, Rodrigue, Amanda L., Zhao, Wei, Yanek, Lisa R., Ratliff, Scott M., Pitsillides, Achilleas, Aguirre Patiño, Juan Sebastian, Sofer, Tamar, Arking, Dan E., Austin, Thomas R., Beiser, Alexa S., Blangero, John, Boerwinkle, Eric, Bressler, Jan, Curran, Joanne E., Hou, Lifang, Hughes, Timothy M., Kardia, Sharon L.R., Launer, Lenore J., Levy, Daniel, Mosley, Thomas H., Nasrallah, Ilya M., Rich, Stephen S., Rotter, Jerome I., Seshadri, Sudha, Tarraf, Wassim, González, Kevin A., Ramachandran, Vasan, Yaffe, Kristine, Nyquist, Paul A., Psaty, Bruce M., DeCarli, Charles S., Smith, Jennifer A., Glahn, David C., González, Hector M., Bis, Joshua C., Fornage, Myriam, Heckbert, Susan R., Fitzpatrick, Annette L., Liu, Chunyu, Satizabal, Claudia L., Aguilera, Norma, Ament, Seth, Ammous, Farah, Arnett, Donna K, Becker, Diane, Bis, Joshua, Blue, Elizabeth, Boerwinkle, Eric, Breaux, Camille, Bressler, Jan, Chaar, Dima, MHI, Clarkson-Townsend, Danielle, Cooper, Brigidann, Coresh, Josef, Correa, Adolfo, DeStefano, Anita, Ding, Jingzhong, Fardo, David, Fitzpatrick, Annette, Fornage, Myriam, French, Jennifer, Glahn, David, Gonzalez, Hector, Granot-Hershkovitz, Einat, Hanly, Patrick, Hayden, Kathleen, Heckbert, Susan, Heemann, Scott, Horvath, Steve, Hoth, Karin, Hughes, Timothy, Jaiswal, Sidd, Jian, Xueqiu, Katsumata, Yuriko, Kho, Minjung, Kooperberg, Charles, Launer, Lenore, Lin, Honghuang, Litkowski, Elizabeth, Longstreth, Will, Martin, Alexandra, Mayeux, Richard, Mikulla, Julie, Miller, Amy, Misra, Biswapriya, Mosley, Thomas, Nyquist, Paul, O'Connell, Jeff, Olivier, Michael, Peloso, Gina, Perry, James, Psaty, Bruce, Purcell, Shaun, Raffield, Laura, Ranaweera, Yugandi, Reiner, Alex, Rotter, Jerome, Sargurupremraj, Muralidharan, Sarnowski, Chloé, Satizabal, Claudia, Schellenberg, Gerard, Schoenbein, Bonnie L, Seshadri, Sudha, Shade, Lincoln, Short, Meghan I, Simino, Jeannette, Smith, Jennifer, Smith, Mallorie, Smoller, Sylvia, Snively, Beverly, Soemedi, Rachel, Sokolow, Sophie, Thorington, Daune, Thornton, Timothy A., Yanek, Lisa, Yang, Qiong, Yu, Miao, Zare, Habil, Zhao, Wei, Abecasis, Goncalo, Abhyankar, Avinash, Aldred, Micheala, Arking, Dan, Ashley-Koch, Allison, Aviv, Abraham, Barnes, Kathleen, Barron-Casella, Emily, Battle, Stephanie, Blackwell, Thomas, Burkardt, Deepika, Castellani, Christina A, Comhair, Suzy, Cooper, Brigidann, Correa, Adolfo, Crockett, Phyllis, de Andrade, Mariza, DeMeo, Dawn, DePaoli, Maria Rizzo, Ding, Jun, Dobski, Christine, Erzurum, Serpil, Farha, Samar, Fetterman, Jessica, Floyd, Caitlin, Fu, Mao, Gist, Amber, Granot-Hershkovitz, Einat, Gu, C. Charles, Heemann, Scott, Hernandez, Ryan, Hong, Yun Soo, Hsu, Yi-Hsiang, Justice, Anne, Lange, Leslie, Levy, Dan, Lin, Honghuang, Liu, Chunyu, Longchamps, Ryan, Ma, Jiantao, Manson, JoAnn, Markus, Tammy, McDonald, Merry-Lynn, McGarvey, Stephen, Mikulla, Julie, Montgomery, Courtney, Musunuri, Rajeeva Lochan, O'Connell, Jeff, Oppong, Richard, Pankratz, Nathan, Qian, Yong, Rotter, Jerome, Shaw, Jessica R, Smith, Albert Vernon, Sofer, Tamar, Streeten, Elizabeth, Tang, Weihong, Taylor, Kent D., Telen, Marilyn, Thompson, Shelby, Thorington, Daune, Tiwari, Hemant, Walsh, Ann, Wan, Emily, Wang, Cuicui, Wang, Heming, Wang, Penglong, Weir, Bruce, Williams, L. Keoki, Wilson, James, Xiao, Shujie, Xu, Weiling, Yang, Yu-Chung, and Zhao, Wei

Published
2023
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6. Sicherheitsaspekte und Vorbereitung zur Notfallvorsorge und Gefahrenabwehr in Kliniken bei MANV/TerrorMANV

Author

Hoth, Patrick, Bieler, Dan, Friemert, Benedikt, Franke, Axel, Blätzinger, Markus, and Achatz, Gerhard

Abstract

Hintergrund: Weltweite terroristische Aktivitäten seit „9/11“ und folgend auch im europäischen Raum haben im Rahmen der Bewertung von kritischer Infrastruktur in Deutschland zu einem Umdenken auch hinsichtlich der Sicherheit an und in Kliniken geführt. Ziel der Arbeit: Die vorliegende Publikation befasst sich mit der Bewertung vorliegender Konzepte zu Themen wie „Alarmierung“, „Sicherheit“, „Kommunikation“ und „Vorbereitung“ im vorgenannten Kontext. Material und Methoden: Anhand einer Literatursichtung sowie einer Umfrage unter den Teilnehmern*innen der 3. Notfallkonferenz der DGU (Deutsche Gesellschaft für Unfallchirurgie) werden diese Thematik und die aktuell vorliegende Situation weiter analysiert und vorgestellt. Ergebnisse: Die gewonnenen Daten verdeutlichen, dass ein Großteil der Kliniken zwar über eine Krankenhausalarm- und Einsatzplanung verfügt, jedoch die Frequenz der Aktualisierungen und die innerklinische Kommunikation zur Steigerung der Wahrnehmung eine deutliche Streuung zeigen. Diskussion: Zusammenfassend scheint die latente Bedrohung durch terroristische Aktivitäten dazu geführt zu haben, dass sich deutsche Kliniken in der Bewertung als kritische Infrastruktur mit der Thematik „Krankenhausalarm- und Einsatzplanung“ auseinandergesetzt und diese überwiegend auch umgesetzt haben. Allerdings zeigt sich für die nachgeordneten Bereiche und die aus der Alarmplanung ableitbaren Konsequenzen noch nicht die nötige Stringenz, um letztendlich adäquate Reaktionen in diesen besonderen Szenarien im Hinblick auf die Sicherheit in und an deutschen Kliniken zu gewährleisten.

Published
2022
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7. Professionalism of Admitting and Consulting Services and Trauma Patient Outcomes

Author

Cooper, William O., Hickson, Gerald B., Guillamondegui, Oscar D., Cannon, Jeremy W, Charles, Anthony G., Hoth, J. Jason, Alam, Hasan B., Tillou, Areti, Luchette, Frederick A., Skeete, Dionne A., Domenico, Henry J., Meredith, J. Wayne, Brennan, Theresa M. H., Smith, Brian P, Kelz, Rachel R., Biesterveld, Ben E., Busuttil, Ashley, Jopling, Jeffrey K., Hopkins, Joseph R., Emory, Cynthia L., Sullivan, Patricia G., Martin, R. Shayn, Howerton, Russell M., Cryer, Henry M., Davidson, Heather A., Gonzalez, Richard P., and Spain, David A.

Published
2022
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8. KIR2DS1–HLA-C status as a predictive marker for benefit from rituximab: a post-hoc analysis of the RICOVER-60 and CLL8 trials

Author

Kaddu-Mulindwa, Dominic, Altmann, Bettina, Robrecht, Sandra, Ziepert, Marita, Regitz, Evi, Tausch, Eugen, Held, Gerhard, Poeschel, Viola, Lesan, Vadim, Bittenbring, Joerg Thomas, Thurner, Lorenz, Pfreundschuh, Michael, Christofyllakis, Konstantinos, Truemper, Lorenz, Loeffler, Markus, Schmitz, Norbert, Hoth, Markus, Hallek, Michael, Fischer, Kirsten, Stilgenbauer, Stephan, Bewarder, Moritz, and Rixecker, Torben Millard

Abstract

The addition of rituximab to chemotherapy has substantially improved outcomes for patients with B-cell malignancies. The mechanisms of action of rituximab include activation of natural killer cells. Killer-cell immunoglobulin-like receptors (KIRs) mediate natural killer cell function through interaction with HLA. We evaluated the clinical impact of KIR–HLA genotypes on rituximab-containing therapy.

Published
2022
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9. Emphysema Progression and Lung Function Decline Among Angiotensin Converting Enzyme Inhibitors and Angiotensin-Receptor Blockade Users in the COPDGene Cohort

Author

Tejwani, Vickram, Fawzy, Ashraf, Putcha, Nirupama, Castaldi, Peter J., Cho, Michael H., Pratte, Katherine A., Bhatt, Surya P., Lynch, David A., Humphries, Stephen M., Kinney, Gregory L., D’Alessio, Franco R., Hansel, Nadia N., Crapo, James D., Silverman, Edwin K., Make, Barry J., Regan, Elizabeth A., Beaty, Terri, Begum, Ferdouse, Castaldi, Peter J., Cho, Michael, DeMeo, Dawn L., Boueiz, Adel R., Foreman, Marilyn G., Halper-Stromberg, Eitan, Hayden, Lystra P., Hersh, Craig P., Hetmanski, Jacqueline, Hobbs, Brian D., Hokanson, John E., Laird, Nan, Lange, Christoph, Lutz, Sharon M., McDonald, Merry-Lynn, Parker, Margaret M., Prokopenko, Dmitry, Qiao, Dandi, Regan, Elizabeth A., Sakornsakolpat, Phuwanat, Silverman, Edwin K., Wan, Emily S., Won, Sungho, Centeno, Juan Pablo, Charbonnier, Jean-Paul, Coxson, Harvey O., Galban, Craig J., Han, MeiLan K., Hoffman, Eric A., Humphries, Stephen, Jacobson, Francine L., Judy, Philip F., Kazerooni, Ella A., Kluiber, Alex, Lynch, David A., Nardelli, Pietro, Newell, John D., Notary, Aleena, Oh, Andrea, Regan, Elizabeth A., Ross, James C., San Jose Estepar, Raul, Schroeder, Joyce, Sieren, Jered, Stoel, Berend C., Tschirren, Juerg, Van Beek, Edwin, Ginneken, Bramvan, van Rikxoort, Eva, Sanchez-Ferrero, Gonzalo Vegas, Veitel, Lucas, Washko, George R., Wilson, Carla G., Jensen, Robert, Everett, Douglas, Crooks, Jim, Pratte, Katherine, Strand, Matt, Wilson, Carla G., Hokanson, John E., Kinney, Gregory, Lutz, Sharon M., Young, Kendra A., Bhatt, Surya P., Bon, Jessica, Diaz, Alejandro A., Han, MeiLan K., Make, Barry, Murray, Susan, Regan, Elizabeth, Soler, Xavier, Wilson, Carla G., Bowler, Russell P., Kechris, Katerina, Banaei-Kashani, Farnoush, Curtis, Jeffrey L., Pernicano, Perry G., Hanania, Nicola, Atik, Mustafa, Boriek, Aladin, Guntupalli, Kalpatha, Guy, Elizabeth, Parulekar, Amit, DeMeo, Dawn L., Diaz, Alejandro A., Hayden, Lystra P., Hobbs, Brian D., Hersh, Craig, Jacobson, Francine L., Washko, George, Barr, R. Graham, Austin, John, D’Souza, Belinda, Thomashow, Byron, MacIntyre, Neil, McAdams, H. Page, Washington, Lacey, Flenaugh, Eric, Terpenning, Silanth, McEvoy, Charlene, Tashjian, Joseph, Wise, Robert, Brown, Robert, Hansel, Nadia N., Horton, Karen, Lambert, Allison, Putcha, Nirupama, Casaburi, Richard, Adami, Alessandra, Budoff, Matthew, Fischer, Hans, Porszasz, Janos, Rossiter, Harry, Stringer, William, Sharafkhaneh, Amir, Lan, Charlie, Wendt, Christine, Bell, Brian, Kunisaki, KenM., Bowler, Russell, Lynch, David A., Rosiello, Richard, Pace, David, Criner, Gerard, Ciccolella, David, Cordova, Francis, Dass, Chandra, D’Alonzo, Gilbert, Desai, Parag, Jacobs, Michael, Kelsen, Steven, Kim, Victor, Mamary, A. James, Marchetti, Nathaniel, Satti, Aditi, Shenoy, Kartik, Steiner, Robert M., Swift, Alex, Swift, Irene, Vega-Sanchez, Maria Elena, Dransfield, Mark, Bailey, William, Bhatt, Surya P., Iyer, Anand, Nath, Hrudaya, Wells, J. Michael, Conrad, Douglas, Soler, Xavier, Yen, Andrew, Comellas, Alejandro P., Hoth, Karin F., Newell, John, Thompson, Brad, Han, MeiLan K., Kazerooni, Ella, Labaki, Wassim, Galban, Craig, Vummidi, Dharshan, Billings, Joanne, Begnaud, Abbie, Allen, Tadashi, Sciurba, Frank, Bon, Jessica, Chandra, Divay, Fuhrman, Carl, and Weissfeld, Joel

Abstract

Attenuation of transforming growth factor β by blocking angiotensin II has been shown to reduce emphysema in a murine model. General population studies have demonstrated that the use of angiotensin converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) is associated with reduction of emphysema progression in former smokers and that the use of ACEis is associated with reduction of FEV1progression in current smokers.

Published
2021
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10. The Association Between Lung Hyperinflation and Coronary Artery Disease in Smokers

Author

Chandra, Divay, Gupta, Aman, Kinney, Gregory L., Fuhrman, Carl R., Leader, Joseph K., Diaz, Alejandro A., Bon, Jessica, Barr, R. Graham, Washko, George, Budoff, Matthew, Hokanson, John, Sciurba, Frank C., Crapo, James D., Silverman, Edwin K., Make, Barry J., Regan, Elizabeth A., Beaty, Terri, Begum, Ferdouse, Boueiz, Adel R., Castaldi, Peter J., Cho, Michael, DeMeo, Dawn L., Foreman, Marilyn G., Halper-Stromberg, Eitan, Hayden, Lystra P., Hersh, Craig P., Hetmanski, Jacqueline, Hobbs, Brian D., Hokanson, John E., Laird, Nan, Lange, Christoph, Lutz, Sharon M., McDonald, Merry-Lynn, Parker, Margaret M., Prokopenko, Dmitry, Qiao, Dandi, Regan, Elizabeth A., Sakornsakolpat, Phuwanat, Silverman, Edwin K., Wan, Emily S., Won, Sungho, Al Qaisi, Mustafa, Coxson, Harvey O., Gray, Teresa, Han, MeiLan K., Hoffman, Eric A., Humphries, Stephen, Jacobson, Francine L., Judy, Philip F., Kazerooni, Ella A., Kluiber, Alex, Lynch, David A., Newell, John D., Regan, Elizabeth A., Ross, James C., San Jose Estepar, Raul, Schroeder, Joyce, Sieren, Jered, Stinson, Douglas, Stoel, Berend C., Tschirren, Juerg, Van Beek, Edwin, Ginneken, Bram van, van Rikxoort, Eva, Washko, George, Wilson, Carla G., Jensen, Robert, Crooks, Jim, Everett, Douglas, Moore, Camille, Strand, Wilson, Carla G., Hokanson, John E., Hughes, John, Kinney, Gregory, Lutz, Sharon M., Pratte, Katherine, Young, Kendra A., Bhatt, Surya, Bon, Jessica, Han, MeiLan K., Make, Barry J., Martinez, Carlos, Murray, Susan, Regan, Elizabeth A., Soler, Xavier, Wilson, Carla G., Banaei-Kashani, Farnoush, Bowler, Russell P., Kechris, Katerina, Curtis, Jeffrey L., Pernicano, Perry G., Hanania, Nicola, Atik, Mustafa, Boriek, Aladin, Guntupalli, Kalpatha, Guy, Elizabeth, Parulekar, Amit, DeMeo, Dawn L., Diaz, Alejandro A., Hayden, Lystra P., Hobbs, Brian D., Hersh, Craig, Jacobson, Francine L., Washko, George, Barr, R. Graham, Austin, John, D’Souza, Belinda, Thomashow, Byron, MacIntyre, Neil, McAdams, H. Page, Washington, Lacey, McEvoy, Charlene, Tashjian, Joseph, Wise, Robert, Brown, Robert, Hansel, Nadia N., Horton, Karen, Lambert, Allison, Putcha, Nirupama, Casaburi, Richard, Adami, Alessandra, Budoff, Matthew, Fischer, Hans, Porszasz, Janos, Rossiter, Harry, Stringer, William, DeBakey, Michael E., Sharafkhaneh, Amir, Lan, Charlie, Wendt, Christine, Bell, Brian, Kunisaki, Ken M., Foreman, Marilyn G., Berkowitz, Eugene, Westney, Gloria, Bowler, Russell, Lynch, David A., Rosiello, Richard, Pace, David, Criner, Gerard, Ciccolella, David, Cordova, Francis, Dass, Chandra, D’Alonzo, Gilbert, Desai, Parag, Jacobs, Michael, Kelsen, Steven, Kim, Victor, Mamary, A. James, Marchetti, Nathaniel, Satti, Aditi, Shenoy, Kartik, Steiner, Robert M., Swift, Alex, Swift, Irene, Vega-Sanchez, Maria Elena, Dransfield, Mark, Bailey, William, Bhatt, Surya P., Iyer, Anand, Nath, Hrudaya, Wells, J. Michael, Ramsdell, Joe, Friedman, Paul, Soler, Xavier, Yen, Andrew, Comellas, Alejandro P., Hoth, Karin F., Newell, John, Thompson, Brad, Han, MeiLan K., Kazerooni, Ella, Martinez, Carlos H., Billings, Joanne, Begnaud, Abbie, Allen, Tadashi, Sciurba, Frank, Bon, Jessica, Chandra, Divay, Fuhrman, Carl, Weissfeld, Joel, Anzueto, Antonio, Adams, Sandra, Maselli-Caceres, Diego, and Ruiz, Mario E.

Abstract

Smokers manifest varied phenotypes of pulmonary impairment.

Published
2021
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11. Pulmonary Arterial Pruning and Longitudinal Change in Percent Emphysema and Lung Function

Author

Pistenmaa, Carrie L., Nardelli, P., Ash, S.Y., Come, C.E., Diaz, A.A., Rahaghi, F.N., Barr, R.G., Young, K.A., Kinney, G.L., Simmons, J.P., Wade, R.C., Wells, J.M., Hokanson, J.E., Washko, G.R., San José Estépar, R., Crapo, James D., Silverman, Edwin K., Make, Barry J., Regan, Elizabeth A., Beaty, Terri H., Castaldi, Peter J., Cho, Michael H., DeMeo, Dawn L., El Boueiz, Adel, Foreman, Marilyn G., Ghosh, Auyon, Hayden, Lystra P., Hersh, Craig P., Hetmanski, Jacqueline, Hobbs, Brian D., Hokanson, John E., Kim, Wonji, Laird, Nan, Lange, Christoph, Lutz, Sharon M., McDonald, Merry-Lynn, Prokopenko, Dmitry, Moll, Matthew, Morrow, Jarrett, Qiao, Dandi, Regan, Elizabeth A., Saferali, Aabida, Sakornsakolpat, Phuwanat, Silverman, Edwin K., Wan, Emily S., Yun, Jeong, Centeno, Juan Pablo, Charbonnier, Jean-Paul, Coxson, Harvey O., Galban, Craig J., Han, MeiLan K., Hoffman, Eric A., Humphries, Stephen, Jacobson, Francine L., Judy, Philip F., Kazerooni, Ella A., Kluiber, Alex, Lynch, David A., Nardelli, Pietro, Newell, John D., Notary, Aleena, Oh, Andrea, Regan, Elizabeth A., Ross, James C., San Jose Estepar, Raul, Schroeder, Joyce, Sieren, Jered, Stoel, Berend C., Tschirren, Juerg, Van Beek, Edwin, Ginneken, Bramvan, van Rikxoort, Eva, Sanchez- Ferrero, Gonzalo Vegas, Veitel, Lucas, Washko, George R., Wilson, Carla G., Jensen, Robert, Everett, Douglas, Crooks, Jim, Pratte, Katherine, Strand, Matt, Wilson, Carla G., Hokanson, John E., Austin, Erin, Kinney, Gregory, Lutz, Sharon M., Young, Kendra A., Bhatt, Surya P., Bon, Jessica, Diaz, Alejandro A., Han, MeiLan K., Make, Barry, Murray, Susan, Regan, Elizabeth, Soler, Xavier, Wilson, Carla G., Bowler, Russell P., Kechris, Katerina, Banaei-Kashani, Farnoush, Curtis, Jeffrey L., Pernicano, Perry G., Hanania, Nicola, Atik, Mustafa, Boriek, Aladin, Guntupalli, Kalpatha, Guy, Elizabeth, Parulekar, Amit, DeMeo, Dawn L., Hersh, Craig, Jacobson, Francine L., Washko, George, Barr, R. Graham, Austin, John, D’Souza, Belinda, Thomashow, Byron, MacIntyre, Neil, McAdams, H. Page, Washington, Lacey, McEvoy, Charlene, Tashjian, Joseph, Wise, Robert, Brown, Robert, Hansel, Nadia N., Horton, Karen, Lambert, Allison, Putcha, Nirupama, Casaburi, Richard, Adami, Alessandra, Budoff, Matthew, Fischer, Hans, Porszasz, Janos, Rossiter, Harry, Stringer, William, Sharafkhaneh, Amir, Lan, Charlie, Wendt, Christine, Bell, Brian, Kunisaki, Ken M., Flenaugh, Eric L., Gebrekristos, Hirut, Ponce, Mario, Terpenning, Silanath, Westney, Gloria, Bowler, Russell, Lynch, David A., Rosiello, Richard, Pace, David, Criner, Gerard, Ciccolella, David, Cordova, Francis, Dass, Chandra, D’Alonzo, Gilbert, Desai, Parag, Jacobs, Michael, Kelsen, Steven, Kim, Victor, Mamary, A. James, Marchetti, Nathaniel, Satti, Aditi, Shenoy, Kartik, Steiner, Robert M., Swift, Alex, Swift, Irene, Vega-Sanchez, Maria Elena, Dransfield, Mark, Bailey, William, Bhatt, Surya P., Iyer, Anand, Nath, Hrudaya, Wells, J. Michael, Conrad, Douglas, Soler, Xavier, Yen, Andrew, Comellas, Alejandro P., Hoth, Karin F., Newell, John, Thompson, Brad, Han, MeiLan K., Kazerooni, Ella, Labaki, Wassim, Galban, Craig, Vummidi, Dharshan, Billings, Joanne, Begnaud, Abbie, Allen, Tadashi, Sciurba, Frank, Bon, Jessica, Chandra, Divay, and Weissfeld, Joel

Abstract

Pulmonary endothelial damage has been shown to precede the development of emphysema in animals, and vascular changes in humans have been observed in COPD and emphysema.

Published
2021
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12. Remediating Oil Contamination in the Niger Delta Region of Nigeria: Technical Options and Monitoring Strategies

Author

Ola, Ibukun, Drebenstedt, Carsten, Burgess, Robert M., Mensah, Martin, Hoth, Nils, and Külls, Christoph

Abstract

The Niger Delta, a region of immense ecological significance and rich biodiversity, has long faced the severe consequences of petroleum contamination resulting from intense oil exploration and various environmental stressors. In response to the pressing need for effective remediation and monitoring of contaminated matrices in the Niger Delta, this study delves into a comprehensive analysis. Through a systematic assessment considering certain criteria, advanced remediation technologies tailored to the specific environmental challenges in the region are identified. Organoclay-based reactive core materials (RCM), permeable reactive barriers (PRBs), and bioremediation have emerged as highly suitable solutions for remediating sediment, groundwater, and soil, respectively. These technologies span the spectrum from non-intrusive to less intrusive methods and have demonstrated exceptional efficacy in mitigating hydrocarbon contamination under the delta's prevailing complex conditions. In addressing the critical need for monitoring the progress of remediation and post-remediation stages, a fully integrated approach is proposed. This strategy combines three essential components for tracking environmental quality improvements and understanding the recovery processes: traditional total chemical concentration (Ctotal) estimates, passive sampler-derived freely dissolved chemical concentration (Cfree) measurements, and ecological monitoring, specifically the recolonization test. Together, these components provide a more accurate description of risk and a comprehensive understanding of the recovery process. This study is concentrated on the systematic selection, supported by credible case study information, of tailored technical solutions for addressing the unique challenges of the Niger Delta. The novel outcomes lie in the identification of technology solutions carefully adapted for the region, representing a significant advancement in the field of environmental remediation in the Niger Delta. Science-based remediation and monitoring are key, and this study offers a decision support tool for selecting optimal methods in the ongoing cleanup of the Niger Delta and similar areas. This supports a healthier, more resilient environment for both the region's inhabitants and ecosystems.

Published
2024
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13. Predictors of HIV Preexposure Prophylaxis Initiation Among Public Health Clients in Rural and Small Urban Areas in Iowa

Author

Howren, M. Bryant, Francis, Shelby L., Polgreen, Linnea A., Shafer, Cody, Hoth, Angela, and Ohl, Michael E.

Abstract

Objective Preexposure prophylaxis (PrEP) is a safe and effective method for HIV prevention, but little is known about PrEP uptake in rural and small urban areas. We described rates and predictors of HIV PrEP initiation among public health clients in rural and small urban areas in Iowa.Methods This was a prospective cohort study of clients with PrEP indications served by HIV testing and disease intervention specialist/partner services (DIS/PS) programs in public health departments in Iowa from February 1, 2018, through February 28, 2019. Eligible participants were aged 18-70 and referred for PrEP by public health personnel. Participants completed surveys at enrollment addressing demographic characteristics; sexual history; previous drug use; PrEP experiences; and knowledge, attitudes, and beliefs about PrEP. A follow-up survey assessed PrEP initiation at 30 days. We compared baseline characteristics of PrEP initiators and non-initiators.Results Two hundred thirty-four public health clients consented to participate in the study; 189 completed the baseline survey, and 117 (61.9%) completed the follow-up survey. The mean age of participants in the baseline survey was 30 (range, 18-68); 109 (57.7%) were male, 127 (67.2%) were White, and 169 (89.4%) lived in a rural or small urban area. Of 117 participants in the follow-up survey, those who initiated PrEP were significantly more likely than those who did not initiate PrEP to be referred by DIS/PS programs (46.7% vs 7.8%, P< .001) and to recognize that PrEP was ≥90% effective (86.7% vs 35.3%, P= .001). No PrEP initiators and 8 PrEP non-initiators agreed that PrEP is for promiscuous people (0% vs 7.8%, P= .04). Perceived PrEP stigma was low and not associated with PrEP initiation.Conclusions PrEP initiation rates were low among rural and small urban health department clients. Interventions are needed to improve linkage to PrEP among rural and small urban public health clients.

Published
2021
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14. Undertriage Despite Use of Geriatric-Specific Trauma Team Activation Guidelines: Who Are We Missing?

Author

Anantha, Ram V., Painter, Matthew D., Diaz-Garelli, Franck, Nunn, Andrew M., Miller, Preston R., Chang, Michael C., and Jason Hoth, J.

Abstract

Background Elderly trauma patients are at risk for undertriage, resulting in substantial morbidity and mortality. The objective of this study was to determine whether implementation of geriatric-specific trauma team activation (TTA) protocols appropriately identified severely-injured elderly patients.Methods This single-center retrospective study evaluated all severely injured (injury severity score [ISS] >15), geriatric (≥65 years) patients admitted to our Level 1 tertiary-care hospital between January 2014 and September 2017. Undertriage was defined as the lack of TTA despite presence of severe injuries. The primary outcome was all-cause in-hospital mortality; secondary outcomes were mortality within 48 hours of admission and urgent hemorrhage control. A multivariable logistic regression analysis was performed to identify predictors of appropriate triage in this study.Results Out of 1039 severely injured geriatric patients, 628 (61%) did not undergo TTA. Undertriaged patients were significantly older and had more comorbidities. In-hospital mortality was 5% and 31% in the undertriaged and appropriately triaged groups, respectively (P< .0001). One percent of undertriaged patients needed urgent hemorrhage control, compared to 6% of the appropriately triaged group (P< .0001). One percent of undertriaged patients died within 48 hours compared to 19% in the appropriately triaged group (P< .0001). Predictors of appropriate triage include GCS, heart rate, systolic blood pressure, lactic acid, ISS, shock, and absenceof dementia, stroke, or alcoholism.Discussion Geriatric-specific TTA guidelines continue to undertriage elderly trauma patients when using ISS as a metric to measure undertriage. However, undertriaged patients have much lower morbidity and mortality, suggesting the geriatric-specific TTA guidelines identify those patients at highest risk for poor outcomes.

Published
2021
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15. Migration of Cytotoxic T Lymphocytes in 3D Collagen Matrices

Author

Sadjadi, Zeinab, Zhao, Renping, Hoth, Markus, Qu, Bin, and Rieger, Heiko

Abstract

CD8+cytotoxic T lymphocytes (CTL) and natural killer cells are the main cytotoxic killer cells of the human body to eliminate pathogen-infected or tumorigenic cells (also known as target cells). To find their targets, they have to navigate and migrate through complex biological microenvironments, a key component of which is the extracellular matrix (ECM). The mechanisms underlying killer cell’s navigation are not well understood. To mimic an ECM, we use a matrix formed by different collagen concentrations and analyze migration trajectories of primary human CTLs. Different migration patterns are observed and can be grouped into three motility types: slow, fast, and mixed. The dynamics are well described by a two-state persistent random walk model, which allows cells to switch between slow motion with low persistence and fast motion with high persistence. We hypothesize that the slow motility mode describes CTLs creating channels through the collagen matrix by deforming and tearing apart collagen fibers and that the fast motility mode describes CTLs moving within these channels. Experimental evidence supporting this scenario is presented by visualizing migrating T cells following each other on exactly the same track and showing cells moving quickly in channel-like cavities within the surrounding collagen matrix. Consequently, the efficiency of the stochastic search process of CTLs in the ECM should strongly be influenced by a dynamically changing channel network produced by the killer cells themselves.

Published
2020
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16. Tobacco industry ownership of pharmaceutical companies: an international survey of people with respiratory disease

Author

Tal-Singer, Ruth, Walsh, Linda, Deuby, Tim, Shaughnessy, Angela, Hoth, Karin F, Gascon, Victor, Hintringer, Susanne, Hass, Nicole, Winders, Tonya, Morgan, Lucy, Thomashow, Byron, and Mannino, David M

Abstract

The 2021 purchase of the respiratory pharmaceutical company Vectura by Phillip Morris International has been criticised by the public health and medical community, as a conflict of interest, with little input to date, from the patient community or the public. To address this gap, the COPD Foundation, along with global partners, surveyed 1196 people with chronic respiratory disease. 70% were bothered by a tobacco company making an inhaler to treat lung conditions and 48% reported that they would want to switch inhalers if they knew that a tobacco company made or sold their inhaler devices. Patients care about who makes the therapies used to treat their diseases.

Published
2022
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17. Crystal structure of human lysosomal acid lipase and its implications in cholesteryl ester storage disease[S]

Author

Rajamohan, Francis, Reyes, Allan R., Tu, Meihua, Nedoma, Nicole L., Hoth, Lise R., Schwaid, Adam G., Kurumbail, Ravi G., Ward, Jessica, and Han, Seungil

Abstract

Lysosomal acid lipase (LAL) is a serine hydrolase that hydrolyzes cholesteryl ester (CE) and TGs delivered to the lysosomes into free cholesterol and fatty acids. LAL deficiency due to mutations in the LAL gene (LIPA) results in accumulation of TGs and cholesterol esters in various tissues of the body leading to pathological conditions such as Wolman's disease and CE storage disease (CESD). Here, we present the first crystal structure of recombinant human LAL (HLAL) to 2.6 Å resolution in its closed form. The crystal structure was enabled by mutating three of the six potential glycosylation sites. The overall structure of HLAL closely resembles that of the evolutionarily related human gastric lipase (HGL). It consists of a core domain belonging to the classical α/β hydrolase-fold family with a classical catalytic triad (Ser-153, His-353, Asp-324), an oxyanion hole, and a “cap” domain, which regulates substrate entry to the catalytic site. Most significant structural differences between HLAL and HGL exist at the lid region. Deletion of the short helix, 238NLCFLLC244, at the lid region implied a possible role in regulating the highly hydrophobic substrate binding site from self-oligomerization during interfacial activation. We also performed molecular dynamic simulations of dog gastric lipase (lid-open form) and HLAL to gain insights and speculated a possible role of the human mutant, H274Y, leading to CESD.

Published
2020
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18. Whole Genome Sequencing Identifies CRISPLD2as a Lung Function Gene in Children With Asthma

Author

Kachroo, Priyadarshini, Hecker, Julian, Chawes, Bo L., Ahluwalia, Tarunveer S., Cho, Michael H., Qiao, Dandi, Kelly, Rachel S., Chu, Su H., Virkud, Yamini V., Huang, Mengna, Barnes, Kathleen C., Burchard, Esteban G., Eng, Celeste, Hu, Donglei, Celedón, Juan C., Daya, Michelle, Levin, Albert M., Gui, Hongsheng, Williams, L. Keoki, Forno, Erick, Mak, Angel C.Y., Avila, Lydiana, Soto-Quiros, Manuel E., Cloutier, Michelle M., Acosta-Pérez, Edna, Canino, Glorisa, Bønnelykke, Klaus, Bisgaard, Hans, Raby, Benjamin A., Lange, Christoph, Weiss, Scott T., Lasky-Su, Jessica A., Abe, Namiko, Abecasis, Goncalo, Albert, Christine, Palmer Allred, Nicholette (Nichole), Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Arking, Dan, Arnett, Donna K., Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Barnard, John, Barnes, Kathleen, Barr, R. Graham, Barron-Casella, Emily, Beaty, Terri, Becker, Diane, Becker, Lewis, Beer, Rebecca, Begum, Ferdouse, Beitelshees, Amber, Benjamin, Emelia, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Boerwinkle, Eric, Borecki, Ingrid, Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Bunting, Karen, Burchard, Esteban, Cardwell, Jonathan, Carty, Cara, Casaburi, Richard, Casella, James, Chaffin, Mark, Chang, Christy, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Chen, Yii-Der Ida, Cho, Michael H., Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L. Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, Das, Sayantan, David, Sean, Davis, Colleen, Daya, Michelle, de Andrade, Mariza, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Do, Ron, Duan, Qing, Duggirala, Ravi, Durda, Peter, Dutcher, Susan, Eaton, Charles, Ekunwe, Lynette, Ellinor, Patrick, Emery, Leslie, Farber, Charles, Farnam, Leanna, Fingerlin, Tasha, Flickinger, Matthew, Fornage, Myriam, Franceschini, Nora, Fu, Mao, Fullerton, Stephanie M., Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Yan, Gass, Margery, Gelb, Bruce, Geng, Xiaoqi (Priscilla), Germer, Soren, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Gu, C. Charles, Guan, Yue, Guo, Xiuqing, Haessler, Jeff, Hall, Michael, Harris, Daniel, Hawley, Nicola, He, Jiang, Heavner, Ben, Heckbert, Susan, Hernandez, Ryan, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hokanson, John, Holly, Kramer, Hong, Elliott, Hoth, Karin, (Agnes) Hsiung, Chao, Huston, Haley, Hwu, Chii Min, Irvin, Marguerite Ryan, Jackson, Rebecca, Jain, Deepti, Jaquish, Cashell, Jhun, Min A., Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kachroo, Priyadarshini, Kang, Hyun Min, Kaplan, Robert, Kardia, Sharon, Kathiresan, Sekar, Kaufman, Laura, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Kinney, Greg, Konkle, Barbara, Kooperberg, Charles, Krauter, Stephanie, Lange, Christoph, Lange, Ethan, Lange, Leslie, Laurie, Cathy, Laurie, Cecelia, LeBoff, Meryl, Lee, Seunggeun Shawn, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Dan, Lewis, Joshua, Li, Yun, Lin, Honghuang, Lin, Keng Han, Liu, Simin, Liu, Yongmei, Loos, Ruth, Lubitz, Steven, Lunetta, Kathryn, Luo, James, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manson, JoAnn, Margolin, Lauren, Martin, Lisa, Mathai, Susan, Mathias, Rasika, McArdle, Patrick, McDonald, Merry-Lynn, McFarland, Sean, McGarvey, Stephen, Mei, Hao, Meyers, Deborah A., Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L., Mitchell, Braxton, Montasser, May E., Musani, Solomon, Mwasongwe, Stanford, Mychaleckyj, Josyf C., Nadkarni, Girish, Naik, Rakhi, Natarajan, Pradeep, Nekhai, Sergei, Nickerson, Deborah, North, Kari, O'Connell, Jeff, O'Connor, Tim, Ochs-Balcom, Heather, Pankow, James, Papanicolaou, George, Parker, Margaret, Parsa, Afshin, Penchev, Sara, Peralta, Juan Manuel, Perez, Marco, Perry, James, Peters, Ulrike, Peyser, Patricia, Phillips, Lawrence S., Phillips, Sam, Pollin, Toni, Post, Wendy, Becker, Julia Powers, Boorgula, Meher Preethi, Preuss, Michael, Prokopenko, Dmitry, Psaty, Bruce, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Raffield, Laura, Ramachandran, Vasan, Rao, D.C., Rasmussen-Torvik, Laura, Ratan, Aakrosh, Redline, Susan, Reed, Robert, Regan, Elizabeth, Reiner, Alex, Rice, Ken, Rich, Stephen, Roden, Dan, Roselli, Carolina, Rotter, Jerome, Ruczinski, Ingo, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sakornsakolpat, Phuwanat, Salimi, Shabnam, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay, Scheller, Christopher, Schmidt, Ellen, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Seidman, Jonathan, Sheehan, Vivien, Shetty, Amol, Shetty, Aniket, Sheu, Wayne Hui-Heng, Shoemaker, M. Benjamin, Silver, Brian, Silverman, Edwin, Smith, Jennifer, Smith, Josh, Smith, Nicholas, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne, Streeten, Elizabeth, Sung, Yun Ju, Su-Lasky, Jessica, Sylvia, Jody, Szpiro, Adam, Sztalryd, Carole, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Tinker, Lesley, Tirschwell, David, Tiwari, Hemant, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wan, Emily, Wang, Fei Fei, Watson, Karol, Weeks, Daniel E., Weir, Bruce, Weiss, Scott, Weng, Lu-Chen, Willer, Cristen, Williams, Kayleen, Williams, L. Keoki, Wilson, Carla, Wilson, James, Wong, Quenna, Xu, Huichun, Yanek, Lisa, Yang, Ivana, Yang, Rongze, Zaghloul, Norann, Zekavat, Maryam, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zheng, Xiuwen, Zhi, Degui, Zhou, Xiang, Zody, Michael, and Zoellner, Sebastian

Abstract

Asthma is a common respiratory disorder with a highly heterogeneous nature that remains poorly understood. The objective was to use whole genome sequencing (WGS) data to identify regions of common genetic variation contributing to lung function in individuals with a diagnosis of asthma.

Published
2019
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19. Households water quality in O’Kiep-South Africa and community perception of related health risks

Author

Erdogan, I.G., Fosso-Kankeu, E., Ntwampe, S.K.O., Waanders, F.B., Hoth, N., Rand, A., and Farrar, T.J.

Abstract

South Africa faced challenges related to potable water quality that has periodically deteriorated, coupled with inconsistent supply of tap water (TW) to households. These challenges are a primary exasperation in the arid O’Kiep region, where the community has few alternatives regarding drinkable water sources. The aim of this study was to assess the quality of drinking TW supplied to the O’Kiep community, focusing on health risks associated with the ingestion of such water. The study included both the quantitative assessment of water quality parameters and a qualitative assessment of adverse human health outcomes experienced by the residents. Furthermore, disease patterns which were associated with ingestion of supplied water were also identified and subjected to appropriate statistical data analyses. Due to the inadequate drinking water supply and shortages in O’Kiep, households often are dependent on water tankers and commercially bottled water, amongst other potential sources of drinkable water. Water samples (n = 53) from O’Kiep’ drinking water supply system (DWSS), that is, n = 3 were collected from source and (n = 50) point-of-use (TW) while the questionnaires were simultaneously administered in households. None of the statistical models suggested physicochemical properties as predictors of any of the health symptoms. Approximately, 88% of community members indicated that the water supplied is often turbid, while a high number of people with teeth discolouration (72%) are living in the area and experience diarrhoea-like symptoms, which are likely to be associated with the ingestion of toxin-contaminated water. This was confirmed by some physiochemical parameters quantified, that is, low dissolved oxygen of 2.0 mg/L, a high electrical conductivity of 595 mg/L, and SO42–and chlorine concentrations of 557 and 47.1 mg/L, respectively, which were not within the range prescribed for drinking water guidelines. Furthermore, a positive confirmatory test indicated the presence of toxins in the water. Therefore, regular monitoring and evaluation of DWSS is essential for this vulnerable community.

Published
2019
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20. Covalent Enzyme Inhibition through Fluorosulfate Modification of a Noncatalytic Serine Residue

Author

Fadeyi, Olugbeminiyi O., Hoth, Lise R., Choi, Chulho, Feng, Xidong, Gopalsamy, Ariamala, Hett, Erik C., Kyne, Robert E., Robinson, Ralph P., and Jones, Lyn H.

Abstract

Irreversible enzyme inhibitors and covalent chemical biology probes often utilize the reaction of a protein cysteine residue with an appropriately positioned electrophile (e.g., acrylamide) on the ligand template. However, cysteine residues are not always available for site-specific protein labeling, and therefore new approaches are needed to expand the toolkit of appropriate electrophiles (“warheads”) that target alternative amino acids. We previously described the rational targeting of tyrosine residues in the active site of a protein (the mRNA decapping scavenger enzyme, DcpS) using inhibitors armed with a sulfonyl fluoride electrophile. These inhibitors subsequently enabled the development of clickable probe technology to measure drug-target occupancy in live cells. Here we describe a fluorosulfate-containing inhibitor (aryl fluorosulfate probe (FS-p1)) with excellent chemical and metabolic stability that reacts selectively with a noncatalytic serine residue in the same active site of DcpS as confirmed by peptide mapping experiments. Our results suggest that noncatalytic serine targeting using fluorosulfate electrophilic warheads could be a suitable strategy for the development of covalent inhibitor drugs and chemical probes.

Published
2024
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21. The Effect of 4-Factor Prothrombin Complex Concentrate to Reverse Factor Xa Inhibitors in Patients With Traumatic Intracranial Hemorrhage

Author

Rauh, Jessica L., Torosian, Taron, Thompson, Anothony, Evangelista, Meagan, and Hoth, Jason

Abstract

The utility of 4-factor prothrombin complex concentrate (4F-PCC) for reversal in patients on factor Xa inhibitors (XaI) is unclear, specifically in mild traumatic brain injury (mTBI). This is a retrospective review over 6 years at a level 1 trauma center of patients presenting with mTBI on XaI comparing outcomes for those that received 4F-PCC to those that did not. 140 patients were included, 103 (74%) of these patients received 4F-PCC while 37 (26%) did not. There was no significant difference in neurologic decline within 48 hours of admission or need for neurosurgical intervention. Interestingly, there was no difference in ICH progression (16% vs 14%, P= .77). In this study, 4F-PCC given after mild traumatic brain injury did not impact ICH progression, neurologic decline, or need for neurosurgical intervention. Although limited in numbers, this study suggests that 4F-PCC is not necessarily required in mTBI and further studies are indicated.

Published
2024
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22. A genetic-association study of circulating coagulation factor VIII and von Willebrand factor levels

Author

de Vries, Paul S., Reventun, Paula, Brown, Michael R., Heath, Adam S., Huffman, Jennifer E., Le, Ngoc-Quynh, Bebo, Allison, Brody, Jennifer A., Temprano-Sagrera, Gerard, Raffield, Laura M., Ozel, Ayse Bilge, Thibord, Florian, Jain, Deepti, Lewis, Joshua P., Rodriguez, Benjmain A. T., Pankratz, Nathan, Taylor, Kent D., Polasek, Ozren, Chen, Ming-Huei, Yanek, Lisa R., Carrasquilla, German D., Marioni, Riccardo E., Kleber, Marcus E., Trégouët, David-Alexandre, Yao, Jie, Li-Gao, Ruifang, Joshi, Peter K., Trompet, Stella, Martinez-Perez, Angel, Ghanbari, Mohsen, Howard, Tom E., Reiner, Alex P., Arvanitis, Marios, Ryan, Kathleen A., Bartz, Traci M., Rudan, Igor, Faraday, Nauder, Linneberg, Allan, Ekunwe, Lynette, Davies, Gail, Delgado, Graciela E., Suchon, Pierre, Guo, Xiuqing, Rosendaal, Frits R., Klaric, Lucija, Noordam, Raymond, van Rooij, Frank, Curran, Joanne E., Wheeler, Marsha M., Osburn, William O., O'Connell, Jeffrey R., Boerwinkle, Eric, Beswick, Andrew, Psaty, Bruce M., Kolcic, Ivana, Souto, Juan Carlos, Becker, Lewis C., Hansen, Torben, Doyle, Margaret F., Harris, Sarah E., Moissl, Angela P., Deleuze, Jean-François, Rich, Stephen S., van Hylckama Vlieg, Astrid, Campbell, Harry, Stott, David J., Soria, Jose Manuel, de Maat, Moniek P. M., Almasy, Laura, Brody, Lawrence C., Auer, Paul L., Abe, Namiko, Abecasis, Gonçalo, Aguet, Francois, Albert, Christine, Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Ardlie, Kristin, Arking, Dan, Arnett, Donna K, Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Ayas, Najib, Balasubramanian, Adithya, Barnard, John, Barnes, Kathleen, Barr, R. Graham, Barron-Casella, Emily, Barwick, Lucas, Beaty, Terri, Beck, Gerald, Becker, Diane, Becker, Lewis, Beer, Rebecca, Beitelshees, Amber, Benjamin, Emelia, Benos, Takis, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Blue, Nathan, Boerwinkle, Eric, Bowden, Donald W., Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Brown, Deborah, Bunting, Karen, Burchard, Esteban, Bustamante, Carlos, Buth, Erin, Cade, Brian, Cardwell, Jonathan, Carey, Vincent, Carrier, Julie, Carson, April P., Carty, Cara, Casaburi, Richard, Casas Romero, Juan P, Casella, James, Castaldi, Peter, Chaffin, Mark, Chang, Christy, Chang, Yi-Cheng, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Ida Chen, Yii-Der, Cho, Michael, Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Chung, Ren-Hua, Clish, Clary, Comhair, Suzy, Conomos, Matthew, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L. Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, David, Sean, Davis, Colleen, Daya, Michelle, de Andrade, Mariza, de las Fuentes, Lisa, de Vries, Paul, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Dinh, Huyen, Doddapaneni, Harsha, Duan, Qing, Dugan-Perez, Shannon, Duggirala, Ravi, Durda, Jon Peter, Dutcher, Susan K., Eaton, Charles, Ekunwe, Lynette, El Boueiz, Adel, Ellinor, Patrick, Emery, Leslie, Erzurum, Serpil, Farber, Charles, Farek, Jesse, Fingerlin, Tasha, Flickinger, Matthew, Fornage, Myriam, Franceschini, Nora, Frazar, Chris, Fu, Mao, Fullerton, Stephanie M., Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Shanshan, Gao, Yan, Gass, Margery, Geiger, Heather, Gelb, Bruce, Geraci, Mark, Germer, Soren, Gerszten, Robert, Ghosh, Auyon, Gibbs, Richard, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Graw, Sharon, Gray, Kathryn J., Grine, Daniel, Gross, Colin, Gu, C. Charles, Guan, Yue, Guo, Xiuqing, Gupta, Namrata, Haessler, Jeff, Hall, Michael, Han, Yi, Hanly, Patrick, Harris, Daniel, Hawley, Nicola L., He, Jiang, Heavner, Ben, Heckbert, Susan, Hernandez, Ryan, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hobbs, Brian, Hokanson, John, Hong, Elliott, Hoth, Karin, Hsiung, Chao (Agnes), Hu, Jianhong, Hung, Yi-Jen, Huston, Haley, Hwu, Chii Min, Irvin, Marguerite Ryan, Jackson, Rebecca, Jain, Deepti, Jaquish, Cashell, Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kang, Hyun Min, Kaplan, Robert, Kardia, Sharon, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Khan, Ziad, Kim, Wonji, Kimoff, John, Kinney, Greg, Konkle, Barbara, Kooperberg, Charles, Kramer, Holly, Lange, Christoph, Lange, Ethan, Lange, Leslie, Laurie, Cathy, Laurie, Cecelia, LeBoff, Meryl, Lee, Jiwon, Lee, Sandra, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Dan, Lewis, Joshua, Li, Xiaohui, Li, Yun, Lin, Henry, Lin, Honghuang, Lin, Xihong, Liu, Simin, Liu, Yongmei, Liu, Yu, Loos, Ruth J. F., Lubitz, Steven, Lunetta, Kathryn, Luo, James, Magalang, Ulysses, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manning, Alisa, Manson, JoAnn, Martin, Lisa, Marton, Melissa, Mathai, Susan, Mathias, Rasika, May, Susanne, McArdle, Patrick, McDonald, Merry-Lynn, McFarland, Sean, McGarvey, Stephen, McGoldrick, Daniel, McHugh, Caitlin, McNeil, Becky, Mei, Hao, Meigs, James, Menon, Vipin, Mestroni, Luisa, Metcalf, Ginger, Meyers, Deborah A, Mignot, Emmanuel, Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L, Mitchell, Braxton D., Moll, Matt, Momin, Zeineen, Montasser, May E., Montgomery, Courtney, Muzny, Donna, Mychaleckyj, Josyf C, Nadkarni, Girish, Naik, Rakhi, Naseri, Take, Natarajan, Pradeep, Nekhai, Sergei, Nelson, Sarah C., Neltner, Bonnie, Nessner, Caitlin, Nickerson, Deborah, Nkechinyere, Osuji, North, Kari, O'Connell, Jeff, O'Connor, Tim, Ochs-Balcom, Heather, Okwuonu, Geoffrey, Pack, Allan, Paik, David T., Palmer, Nicholette, Pankow, James, Papanicolaou, George, Parker, Cora, Peloso, Gina, Peralta, Juan Manuel, Perez, Marco, Perry, James, Peters, Ulrike, Peyser, Patricia, Phillips, Lawrence S, Pleiness, Jacob, Pollin, Toni, Post, Wendy, Becker, Julia Powers, Boorgula, Meher Preethi, Preuss, Michael, Psaty, Bruce, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Raffield, Laura, Rajendran, Mahitha, Ramachandran, Vasan S., Rao, D. C., Rasmussen-Torvik, Laura, Ratan, Aakrosh, Redline, Susan, Reed, Robert, Reeves, Catherine, Regan, Elizabeth, Reiner, Alex, Reupena, Muagututi‘a Sefuiva, Rice, Ken, Rich, Stephen, Robillard, Rebecca, Robine, Nicolas, Roden, Dan, Roselli, Carolina, Rotter, Jerome, Ruczinski, Ingo, Runnels, Alexi, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sabino, Ester Cerdeira, Saleheen, Danish, Salimi, Shabnam, Salvi, Sejal, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay G., Santibanez, Jireh, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Seidman, Jonathan, Sériès, Frédéric, Sheehan, Vivien, Sherman, Stephanie L., Shetty, Amol, Shetty, Aniket, Hui-Heng Sheu, Wayne, Shoemaker, M. Benjamin, Silver, Brian, Silverman, Edwin, Skomro, Robert, Smith, Albert Vernon, Smith, Jennifer, Smith, Josh, Smith, Nicholas, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Snyder, Michael, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne M., Storm, Garrett, Streeten, Elizabeth, Su, Jessica Lasky, Sung, Yun Ju, Sylvia, Jody, Szpiro, Adam, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent D., Taylor, Matthew, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Threlkeld, Machiko, Tinker, Lesley, Tirschwell, David, Tishkoff, Sarah, Tiwari, Hemant, Tong, Catherine, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, Van Den Berg, David, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wang, Fei Fei, Wang, Heming, Wang, Jiongming, Watson, Karol, Watt, Jennifer, Weeks, Daniel E., Weinstock, Joshua, Weir, Bruce, Weiss, Scott T, Weng, Lu-Chen, Wessel, Jennifer, Willer, Cristen, Williams, Kayleen, Williams, L. Keoki, Wilson, Carla, Wilson, James, Winterkorn, Lara, Wong, Quenna, Wu, Joseph, Xu, Huichun, Yanek, Lisa, Yang, Ivana, Yu, Ketian, Zekavat, Seyedeh Maryam, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zhu, Xiaofeng, Ziv, Elad, Zody, Michael, Zoellner, Sebastian, Lindstrom, Sara, Wang, Lu, Smith, Erin N., Gordon, William, van Hylckama Vlieg, Astrid, de Andrade, Mariza, Brody, Jennifer A., Pattee, Jack W., Haessler, Jeffrey, Brumpton, Ben M., Chasman, Daniel I., Suchon, Pierre, Chen, Ming-Huei, Turman, Constance, Germain, Marine, Wiggins, Kerri L., MacDonald, James, Braekkan, Sigrid K., Armasu, Sebastian M., Pankratz, Nathan, Jackson, Rabecca D., Nielsen, Jonas B., Giulianini, Franco, Puurunen, Marja K., Ibrahim, Manal, Heckbert, Susan R., Bammler, Theo K., Frazer, Kelly A., McCauley, Bryan M., Taylor, Kent, Pankow, James S., Reiner, Alexander P., Gabrielsen, Maiken E., Deleuze, Jean-François, O'Donnell, Chris J., Kim, Jihye, McKnight, Barbara, Kraft, Peter, Hansen, John-Bjarne, Rosendaal, Frits R., Heit, John A., Psaty, Bruce M., Tang, Weihong, Kooperberg, Charles, Hveem, Kristian, Ridker, Paul M., Morange, Pierre-Emmanuel, Johnson, Andrew D., Kabrhel, Christopher, AlexandreTrégouët, David, Smith, Nicholas L., Mitchell, Braxton D., Ben-Shlomo, Yoav, Fornage, Myriam, Hayward, Caroline, Mathias, Rasika A., Kilpeläinen, Tuomas O., Lange, Leslie A., Cox, Simon R., März, Winfried, Morange, Pierre-Emmanuel, Rotter, Jerome I., Mook-Kanamori, Dennis O., Wilson, James F., van der Harst, Pim, Jukema, J. Wouter, Ikram, M. Arfan, Blangero, John, Kooperberg, Charles, Desch, Karl C., Johnson, Andrew D., Sabater-Lleal, Maria, Lowenstein, Charles J., Smith, Nicholas L., and Morrison, Alanna C.

Abstract

•We identified 7 new genetic regions for factor VIII levels, 1 for von Willebrand factor levels, and 3 in a combined analysis.•Silencing B3GNT2and CD36reduced factor VIII release in vitro.Silencing B3GNT2, CD36, and PDIA3reduced von Willebrand factor release.

Published
2024
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23. Factors associated with the decision to receive bivalent COVID-19 booster vaccination among health care personnel

Author

Mohr, Nicholas M., Plumb, Ian D., Santos León, Eliezer, Harland, Karisa K., Krishnadasan, Anusha, Nandi, Utsav, Hoth, Karin F., Smithline, Howard A., and Talan, David A.

Abstract

ABSTRACTCOVID-19 vaccination is effective at reducing SARS-CoV-2 complications, but uptake has been low. Our objective in this study was to compare the importance of factors reported to influence the decision to receive a bivalent COVID-19 booster vaccine among health care personnel (HCP) tested for SARS-CoV-2 between October 2022 and April 2023 in a 20-hospital vaccine effectiveness study in the United States (n = 1656). Compared with those who had not received the booster, the factors most likely to be reported to be important were concerns about contracting COVID-19 (84.0% of those who had received the bivalent booster vs. 47.5% of those who had not, difference 36.6% points (PP), 95% confidence interval [CI] 32.1 to 41.1%), spreading infection to family members (89.2% vs. 62.8%, difference 26.3 PP, 95% CI 22.3 to 30.4%), and spreading infection to colleagues at work (85.5% vs. 59.4%, difference 26.1 PP, 95% CI 21.7 to 30.5%). HCP who had received the booster more frequently cited the primary literature (61.7% vs. 31.8%, difference 29.9 PP, 95% CI 24.6 to 35.2%) and employer recommendations (48.3% vs. 29.8%, difference 18.5 PP, 95% CI 13.2 to 23.9%) as influencing their decision. This analysis provides insight into factors for targeting future vaccine messaging.

Published
2023
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26. Review-Quantification of Hydrogen Peroxide by Electrochemical Methods and Electron Spin Resonance Spectroscopy

Author

Gulaboski, Rubin, Mirceski, Valentin, Kappl, Reinhard, Hoth, Markus, and Bozem, Monika

Abstract

Reactive oxygen species (ROS) exhibit different spatial and temporal distributions as well as concentrations in- and outside the cell, thereby functioning as signaling or pathogen-destroying molecules. Especially the ROS H2O2 is important for the patho/physiological status of an organism. Electrochemistry (EM) and electron spin resonance (ESR)-based techniques allow quantification of H2O2 in artificial and living systems, coping a concentration range from low nM up to mM. Working electrodes for EM are optimized by diverse modifications and, additionally, redox mediators are used. Ultramicroelectrodes allow scanning of single cells to spatially resolve and quantify extracellular H2O2 in real-time. With ESR spectroscopy, *O2-, but not H2O2, can be directly determined by spin probes in- and outside of cells in suspensions. Monitoring H2O2 requires formation of intermediate radicals, detectable with spin probes. Low uM [H2O2] can thus be assessed specifically. Using suitable spin traps, in-vivo ESR and immuno-spin trapping can visualize different radicals at their respective production sites in small animals, organs and tissues. Here, the redox reaction cascades may interfere with cell metabolism. Optimization of all methods established for H2O2 determination would be favorable to finally combine them for mutual validation. Thus, a deeper insight into cellular ROS metabolism can be obtained.

Published
2019

27. An APOOPseudogene on Chromosome 5q Is Associated With Low-Density Lipoprotein Cholesterol Levels

Author

Montasser, May E., O’Hare, Elizabeth A., Wang, Xiaochun, Howard, Alicia D., McFarland, Rebecca, Perry, James A., Ryan, Kathleen A., Rice, Kenneth, Jaquish, Cashell E., Shuldiner, Alan R., Miller, Michael, Mitchell, Braxton D., Zaghloul, Norann A., Chang, Yen-Pei C., Abe, Namiko, Abecasis, Goncalo, Albert, Christine, Allred, Nicholette P., Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Debora, Arking, Dan, Arnett, Donna K, Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Barnard, John, Barnes, Kathleen, Graham Barr, R., Barron-Casella, Emily, Beaty, Terri, Becker, Diane, Becker, Lewis, Beer, Rebecca, Begum, Ferdouse, Beitelshees, Amber, Benjamin, Emelia, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Boerwinkle, Eric, Borecki, Ingrid, Bowler, Russel, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Bunting, Karen, Burchard, Esteban, Cardwell, Jonathan, Carlson, Sara, Carty, Cara, Casaburi, Richard, Casella, James, Chaffin, Mark, Chang, Christy, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Ida Chen, Yii-Der, Cho, Michael, Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, Das, Sayantan, David, Sean, Davis, Colleen, Daya, Michelle, de Andrade, Mariza, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Do, Ron, Duan, Qing, Duggirala, Ravi, Durda, Peter, Dutcher, Susan, Eaton, Charles, Ekunwe, Lynette, Ellinor, Patrick, Emery, Leslie, Farber, Charles, Farnam, Leanna, Fingerlin, Tasha, Flickinger, Matthew, Fornage, Myriam, Franceschini, Nora, Fu, Mao, Fullerton, Malia, Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Yan, Gass, Margery, Gelb, Bruce, Geng, Xiaoqi (Priscilla), Germer, Soren, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Charles Gu, C., Guan, Yue, Guo, Xiuqing, Haessler, Jeff, Hall, Michael, Harris, Daniel, Hawley, Nicola, He, Jiang, Heavner, Ben, Heckbert, Susan, Hernandez, Ryan, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hokanson, John, Hong, Elliott, Hoth, Karin, Hsiung, Chao (Agnes), Huston, Haley, Hwu, Chii Min, Irvin, Marguerite, Jackson, Rebecca, Jain, Deepti, Jaquish, Cashell, Jhun, Min A, Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kang, Hyun Min, Kaplan, Robert, Kardia, Sharon, Kathiresan, Sekar, Kaufman, Laura, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Kinney, Greg, Konkle, Barbara, Kooperberg, Charles, Kramer, Holly, Krauter, Stephanie, Lange, Christoph, Lange, Ethan, Lange, Leslie, Laurie, Cathy, Laurie, Cecelia, LeBoff, Meryl, Lee, Seunggeun, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Dan, Lewis, Joshua, Li, Yun, Lin, Honghuang, Lin, Keng Han, Liu, Simin, Liu, Yongmei, Loos, Ruth, Lunetta, Kathryn, Luo, James, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manson, JoAnn, Margolin, Lauren, Martin, Lisa, Mathai, Susan, Mathias, Rasika, McArdle, Patrick, McDonald, Merry-Lynn, McFarland, Sean, McGarvey, Stephen, Mei, Hao, Meyers, Deborah, Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L, Mitchell, Braxton, Musani, Solomon, Mwasongwe, Stanford, Mychaleckyj, Josyf C, Nadkarni, Girish, Naik, Rakhi Johns, Natarajan, Pradeep, Nekhai, Sergei, Nickerson, Deborah, North, Kari, O’Connell, Jeff, O’Connor, Tim, Heather, Ochs-Balcom, Pankow, James, Papanicolaou, George, Parker, Margaret, Parsa, Afshin, Pattison, Jessica Tangarone, Penchev, Sara, Peralta, Juan Manuel, Perez, Marco, Perry, James, Peters, Ulrike, Peyser, Patricia, Phillips, Larry, Phillips, Sam, Pollin, Toni, Post, Wendy, Becker, Julia Powers, Boorgula, Meher Preethi, Preuss, Michael, Prokopenko, Dmitry, Psaty, Bruce, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Raffield, Laura, Ramachandran, Vasan, Rao, D.C., Rasmussen-Torvik, Laura, Ratan, Aakrosh, Redline, Susan, Reed, Robert, Regan, Elizabeth, Reiner, Alex, Rice, Ken, Rich, Stephen, Roden, Dan, Roselli, Carolina, Rotter, Jerome, Ruczinski, Ingo, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sakornsakolpat, Phuwanat, Salimi, Shabnam, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay, Scheller, Christopher, Schmidt, Ellen, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Sheehan, Vivien, Shetty, Amol, Shetty, Aniket, Hui-Heng Sheu, Wayne, Benjamin Shoemaker, M., Silver, Brian, Silverman, Edwin, Smith, Jennifer, Smith, Josh, Smith, Nicholas, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne, Streeten, Elizabeth, Sung, Yun Ju, Sylvia, Jody, Szpiro, Adam, Sztalryd, Carole, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Tinker, Lesley, Tirschwell, David, Tiwari, Hemant, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wan, Emily, Fei Wang, Fei, Watson, Karol, Weeks, Daniel E., Weir, Bruce, Weiss, Scott, Weng, Lu-Chen, Willer, Cristen, Williams, Kayleen, Keoki Williams, L., Wilson, Carla, Wilson, James, Wong, Quenna, Xu, Huichun, Yanek, Lisa, Yang, Ivana, Yang, Rongze, Zaghloul, Norann, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zheng, Xiuwen, Zhi, Degui, Zhou, Xiang, Zody, Michael, and Zoellner, Sebastian

Abstract

Supplemental Digital Content is available in the text.

Published
2018
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30. Association of serum homocysteine, folate, and vitamin B12and mood following the Swank and Wahls elimination dietary interventions in relapsing-remitting multiple sclerosis: Secondary analysis of the WAVES trial

Author

Shemirani, Farnoosh, Titcomb, Tyler J., Saxby, Solange M., Eyck, Patrick Ten, Rubenstein, Linda M., Hoth, Karin F., Snetselaar, Linda G., and Wahls, Terry L.

Abstract

•Both diets had significant improvements in anxiety and depression scores.•Serum levels of homocysteine were reduced, and folate and vitamin B12increased.•No association of depressive symptoms changes with serum homocysteine or vitamin B12.

Published
2023
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32. Patient Experiences with a Tertiary Care Post-COVID-19 Clinic

Author

Garg, Alpana, Subramain, Maran, Barlow, Patrick B, Garvin, Lauren, Hoth, Karin F, Dukes, Kimberly, Hoffman, Richard M, and Comellas, Alejandro P

Abstract

Post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC) is a complex condition with multisystem involvement. We assessed patients’ experience with a PASC clinic established at University of Iowa in June 2020. A survey was electronically mailed in June 2021 asking about (1) symptoms and their impact on functional domains using the Patient-Reported Outcomes Measurement Information System (PROMIS) measures (Global Health and Cognitive Function Abilities) (2) satisfaction with clinic services, referrals, barriers to care, and recommended support resources. Survey completion rate was 35% (97/277). Majority were women (67%), Caucasian (93%), and were not hospitalized (76%) during acute COVID-19. As many as 50% reported wait time between 1 and 3 months, 40% traveled >1 h for an appointment and referred to various subspecialities. Participants reported high symptom burden-fatigue (77%), “brain fog” (73%), exercise intolerance (73%), anxiety (63%), sleep difficulties (56%) and depression (44%). On PROMIS measures, some patients scored significantly low (≥1.5 SD below mean) in physical (22.7%), mental (15.9%), and cognitive (17.6%) domains. Approximately 61% to 93% of participants were satisfied with clinical services. Qualitative analysis added insight to their experience with healthcare. Participants suggested potential strategies for optimizing recovery, including continuity of care, a co-located multispecialty clinic, and receiving timely information from emerging research. Participants appreciated that physicians validated their symptoms and provided continuity of care and access to specialists.

Published
2023
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34. Age-Related Differences in Health-Related Quality of Life in COPD

Author

Martinez, Carlos H., Diaz, Alejandro A., Parulekar, Amit D., Rennard, Stephen I., Kanner, Richard E., Hansel, Nadia N., Couper, David, Holm, Kristen E., Hoth, Karin F., Curtis, Jeffrey L., Martinez, Fernando J., Hanania, Nicola A., Regan, Elizabeth A., Paine, Robert, Cigolle, Christine T., and Han, MeiLan K.

Abstract

Younger persons with COPD report worse health-related quality of life (HRQL) than do older individuals. The factors explaining these differences remain unclear. The objective of this article was to explore factors associated with age-related differences in HRQL in COPD.

Published
2016
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35. Statistical Analysis of Consumer Perceived Value Deviation

Author

Amini, Payam, Falk, Björn, Hoth, Nils C., and Schmitt, Robert H.

Abstract

The lack of integration of customer requirements throughout the product development process can lead to over-engineering or performance gaps, which may result in the failure of a product or innovation. From the company's point of view, the lack of integration can lead to instabilities during ramp-up. However, a high level of product maturity in early stages is of very great importance for the ramp-up. Consumers perceive the value of durable goods in the consumption process at two different points of time. The perceived value based on first impressions influences their buying behavior. In the subsequent usage phase consumers form a new value judgment that affects the repurchase behavior. Conversely, the survey methods to represent the pre-purchase and post-purchase value judgment are not sufficiently discussed in the literature. In this sense, a survey instrument was developed that can be used at both time points to asses the deviation of pre-purchase and post-purchase value judgments. This paper represents the results of the statistical analysis, whether the pre-purchase-value differs significantly from the post-purchase-value. Furthermore, it is examined whether a statement about the consumer's willingness to pay can be made on the basis of the perceived value. The knowledge about the deviation of perceived value have implications for the product maturity and thus during ramp-up.

Published
2016
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37. SIRT1 mediates a primed response to immune challenge after traumatic lung injury

Author

Smith, Lane M., Wells, Jonathan D., Vachharajani, Vidula T., Yoza, Barbara K., McCall, Charles E., and Hoth, J. Jason

Abstract

Pulmonary contusion (PC) is a common, potentially lethal injury that results in priming for exaggerated inflammatory responses to subsequent immune challenge like infection (second hit). The molecular mechanism of priming and the second hit phenomenon after PC remain obscure. With the use of a mouse model of PC, this study explores the role of sirtuin 1 (SIRT1), an NAD-dependent deacetylase, in priming for a second hit after injury.

Published
2015
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38. Inhibitor of Tyrosine Hydroxylase and Catecholamine-induced Cardiomyopathy in Pheochromocytoma

Author

Bouillet, Elise, Hoth-Guechot, Hélène, Vantyghem, Marie-Christine, Pentiah, Anju Duva, Pigny, Pascal, Carnaille, Bruno, Cardot-Bauters, Catherine, and Espiard, Stéphanie

Abstract

Usual clinical presentation of secreting pheochromocytoma is headache, palpitations, sweating and paroxysmal hypertension but emergency situations are also described. We herein reported a case of pheochromocytoma revealed by cardiogenic shock on dilated cardiomyopathy with improvement of left ventricular ejection fraction (LVEF) after the introduction of an inhibitor of tyrosine hydroxylase. A 41-year-old patient was admitted in the ICU for cardiogenic shock with initially hypertension emergency and tachycardia. Transthoracic echocardiography revealed a dilated cardiomyopathy with estimated 2-dimensional LVEF at 15 %. A computed tomography angiography was performed to rule out a pulmonary embolism and led to discover bilateral adrenal tumors measured at 3cm and 2cm respectively on the left and right sides. Plasmatic noradrenaline was increased 5.5μg/L (N<0.60). 123I-metaiodobenzylguanidine scintigraphy, 18F-fluorodeoxyglucose and FDOPA positron emission tomography showed uptake of the 2 lesions. Despite an optimized heart failure treatment including an angiotensin-converting-enzyme inhibitor, a diuretic, an inhibitor of aldosterone and increasing doses of beta-blocker in addition to a calcic-blocker and alpha-blocker for hypertension, a stagnation of LVEF around 20 % was still observed ten weeks after diagnosis, contraindicating the patient for adrenal surgery. The addition of an inhibitor of tyrosine hydroxylase (metyrosine, 1500mg/day) led to a dramatic decrease of blood metanephrines (0.21 versus 1.42μg/L before the introduction), even if results must be interpreted with caution regarding possible interference with this different medicine. Moreover, LVEF improved up to 40 % within 22 weeks allowing the bilateral adrenelactomy. Pathology results confirmed the diagnosis of benign bilateral pheochromocytomas. Genetic analysis showed a MAX mutation (c.145T>C, p.S49P). Congestive heart failure has a poor prognosis unless a correctable cause is identified. For the treatment of pheochromocytoma, surgical removal of tumor is the first choice but in particular cases, using an inhibitor of tyrosine hydroxylase could be a short-term alternative in preparation to surgery.

Published
2021
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39. Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial

Author

Stilgenbauer, Stephan, Schnaiter, Andrea, Paschka, Peter, Zenz, Thorsten, Rossi, Marianna, Döhner, Konstanze, Bühler, Andreas, Böttcher, Sebastian, Ritgen, Matthias, Kneba, Michael, Winkler, Dirk, Tausch, Eugen, Hoth, Patrick, Edelmann, Jennifer, Mertens, Daniel, Bullinger, Lars, Bergmann, Manuela, Kless, Sabrina, Mack, Silja, Jäger, Ulrich, Patten, Nancy, Wu, Lin, Wenger, Michael K., Fingerle-Rowson, Günter, Lichter, Peter, Cazzola, Mario, Wendtner, Clemens M., Fink, Anna M., Fischer, Kirsten, Busch, Raymonde, Hallek, Michael, and Döhner, Hartmut

Abstract

Mutations in TP53, NOTCH1, and SF3B1 were analyzed in the CLL8 study evaluating first-line therapy with fludarabine and cyclophosphamide (FC) or FC with rituximab (FCR) among patients with untreated chronic lymphocytic leukemia (CLL). TP53, NOTCH1, and SF3B1 were mutated in 11.5%, 10.0%, and 18.4% of patients, respectively. NOTCH1mut and SF3B1mut virtually showed mutual exclusivity (0.6% concurrence), but TP53mut was frequently found in NOTCH1mut (16.1%) and in SF3B1mut (14.0%) patients. There were few significant associations with clinical and laboratory characteristics, but genetic markers had a strong influence on response and survival. In multivariable analyses, an independent prognostic impact was found for FCR, thymidine kinase (TK) ≥10 U/L, unmutated IGHV, 11q deletion, 17p deletion, TP53mut, and SF3B1mut on progression-free survival; and for FCR, age ≥65 years, Eastern Cooperative Oncology Group performance status ≥1, β2-microglobulin ≥3.5 mg/L, TK ≥10 U/L, unmutated IGHV, 17p deletion, and TP53mut on overall survival. Notably, predictive marker analysis identified an interaction of NOTCH1 mutational status and treatment in that rituximab failed to improve response and survival in patients with NOTCH1mut. In conclusion, TP53 and SF3B1 mutations appear among the strongest prognostic markers in CLL patients receiving current-standard first-line therapy. NOTCH1mut was identified as a predictive marker for decreased benefit from the addition of rituximab to FC. This study is registered at www.clinicaltrials.gov as #NCT00281918.

Published
2014
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40. Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial

Author

Stilgenbauer, Stephan, Schnaiter, Andrea, Paschka, Peter, Zenz, Thorsten, Rossi, Marianna, Döhner, Konstanze, Bühler, Andreas, Böttcher, Sebastian, Ritgen, Matthias, Kneba, Michael, Winkler, Dirk, Tausch, Eugen, Hoth, Patrick, Edelmann, Jennifer, Mertens, Daniel, Bullinger, Lars, Bergmann, Manuela, Kless, Sabrina, Mack, Silja, Jäger, Ulrich, Patten, Nancy, Wu, Lin, Wenger, Michael K., Fingerle-Rowson, Günter, Lichter, Peter, Cazzola, Mario, Wendtner, Clemens M., Fink, Anna M., Fischer, Kirsten, Busch, Raymonde, Hallek, Michael, and Döhner, Hartmut

Abstract

Mutations in TP53, NOTCH1, and SF3B1were analyzed in the CLL8 study evaluating first-line therapy with fludarabine and cyclophosphamide (FC) or FC with rituximab (FCR) among patients with untreated chronic lymphocytic leukemia (CLL). TP53, NOTCH1,and SF3B1were mutated in 11.5%, 10.0%, and 18.4% of patients, respectively. NOTCH1mutand SF3B1mutvirtually showed mutual exclusivity (0.6% concurrence), but TP53mutwas frequently found in NOTCH1mut(16.1%) and in SF3B1mut(14.0%) patients. There were few significant associations with clinical and laboratory characteristics, but genetic markers had a strong influence on response and survival. In multivariable analyses, an independent prognostic impact was found for FCR, thymidine kinase (TK) ≥10 U/L, unmutated IGHV, 11q deletion, 17p deletion, TP53mut, and SF3B1muton progression-free survival; and for FCR, age ≥65 years, Eastern Cooperative Oncology Group performance status ≥1, β2-microglobulin ≥3.5 mg/L, TK ≥10 U/L, unmutated IGHV, 17p deletion, and TP53muton overall survival. Notably, predictive marker analysis identified an interaction of NOTCH1mutational status and treatment in that rituximab failed to improve response and survival in patients with NOTCH1mut. In conclusion, TP53and SF3B1mutations appear among the strongest prognostic markers in CLL patients receiving current-standard first-line therapy. NOTCH1mutwas identified as a predictive marker for decreased benefit from the addition of rituximab to FC. This study is registered at www.clinicaltrials.govas #NCT00281918.

Published
2014
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41. Complement mediates a primed inflammatory response after traumatic lung injury

Author

Hoth, J. Jason, Wells, Jonathan D., Jones, Sarah E., Yoza, Barbara K., and McCall, Charles E.

Abstract

Pulmonary contusion (PC) is a common, potentially lethal injury that results in the priming for exaggerated responses to subsequent immune challenge such as an infection (second hit). We hypothesize a PC-induced complement (C) activation participates in the priming effect for a second hit.

Published
2014
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42. First Clinical Experiences With a Direct Acoustic Cochlear Stimulator in Comparison to Preoperative Fitted Conventional Hearing Aids

Author

Busch, Susan, Kruck, Stefanie, Spickers, Dirk, Leuwer, Rudolf, Hoth, Sebastian, Praetorius, Mark, Plinkert, Peter K., Mojallal, Hamidreza, Schwab, Burkard, Maier, Hannes, and Lenarz, Thomas

Abstract

Patients with moderate-to-severe mixed hearing losses (MHLs) are hard to provide sufficient benefit with currently available conventional hearing aids. Here, the long-term safety of a direct acoustic cochlear stimulator (DACS) and the effectiveness compared with conventional “high-performance” hearing aids were investigated.

Published
2013
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43. Profilin 1 Potentiates Apoptosis Induced by Staurosporine in Cancer Cells

Author

Yao, W., Cai, X., Liu, C., Qin, Y., Cheng, H., Ji, S., Xu, W., Wu, C., Chen, T., Xu, J., Long, J., Fang, Z., Qu, B., Hoth, M., Ni, Q., Zha, X., and Yu, X.

Abstract

The correlation between the loss of Profilin 1 (Pfn1) with tumor progression indicated that Pfn1 is a tumor suppressor in human carcinoma. The molecular mechanisms underlying Pfn1 tumor suppression has yet to be elucidated. In this study, we showed that Pfn1 overexpression sensitizes cancer cells to apoptosis through the typical intrinsic apoptotic pathway. Mechanistically, the increased Pfn1 expression mediated the upregulation of p53R273H, one of the most common tumor-associated hotspot mutations of p53, with transactivation deletion in tumorigenesis and increased localization of p53R273H in cytoplasm. Further studies showed that mutant p53R273H was involved in apoptosis induced by Staurosporine (STS) via transcriptionindependent mitochondrial functions. We observed (i) the increased cytosolic localization of p53R273H, (ii) the activation of phosphorylation at Ser15, (iii) its mitochondrial localization; Pfn1 acted as a positive regulator of these processes. We also found that Pfn1 interacted with p53R273H and thus facilitated its exertion over the transcription-independent activity in the cytoplasm during drug action. Our results define a new function and mechanism of Pfn1 demonstrating that the combined effect with apoptotic agents led to a synergistic increase in apoptosis. In addition, p53R273H abrogating DNA binding was found to play a major role in the Pfn1- sensitized apoptosis through a transactivation-independent and cytosolic activity.

Published
2013

45. An innovative approach to predict the development of adult respiratory distress syndrome in patients with blunt trauma

Author

Becher, Robert D., Colonna, Alexander L., Enniss, Toby M., Weaver, Ashley A., Crane, Daniel K., Martin, R. Shayn, Mowery, Nathan T., Miller, Preston R., Stitzel, Joel D., and Hoth, J. Jason

Abstract

Pulmonary contusion (PC) is a common injury associated with blunt chest trauma. Complications such as pneumonia and adult respiratory distress syndrome (ARDS) occur in up to 50 of patients with PC. The ability to predict which PC patients are at increased risk of developing complications would be of tremendous clinical utility. In this study, we test the hypothesis that a novel method that objectively measures percent PC can be used to identify patients at risk to develop ARDS after injury.

Published
2012
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46. Does Acute Physiology and Chronic Health Evaluation II Provide a Valid Metric to Directly Compare Disease Severity in Trauma versus Surgical Intensive Care Unit Patients?

Author

Becher, Robert D., Chang, Michael C., Hoth, J. Jason, Kendall, Jennifer L., Beard, H. Randall, and Miller, Preston R.

Abstract

The Acute Physiology and Chronic Health Evaluation II (APACHE II) score has never been validated to risk-adjust between critically ill trauma (TICU) and general surgical (SICU) intensive care unit patients, yet it is commonly used for such a purpose. To study this, we evaluated risk of death in TICU and SICU patients with pneumonia. We hypothesized that mortality for a given APACHE II would be significantly different and that using APACHE II to directly compare TICU and SICU patients would not be appropriate. We conducted a retrospective review of patients admitted to the TICU or SICU at a tertiary medical center over an 18-month period with pneumonia. Admission APACHE II scores, in-hospital mortality, demographics, and illness characteristics were recorded. One hundred eighty patients met inclusion criteria, 116 in the TICU and 64 in the SICU. Average APACHE II scores were not significantly different in the TICU versusSICU (25 vs24; P= 0.4607), indicating similar disease severity; overall mortality rates, however, were significantly different (24 vs50%; P= 0.0004). Components of APACHE II, which contributed to this mortality differential, were Glasgow Coma Score, age, presence of chronic health problems, and operative intervention. APACHE II fails to provide a valid metric to directly compare the severity of disease between TICU and SICU patients with pneumonia. These groups represent distinct populations and should be separated when benchmarking outcomes or creating performance metrics in ICU patients. Improved severity scoring systems are needed to conduct clinically relevant and methodologically valid comparisons between these unique groups.

Published
2012
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47. Systemic inflammation worsens outcomes in emergency surgical patients

Author

Becher, Robert D., Hoth, J. Jason, Miller, Preston R., Meredith, J. Wayne, and Chang, Michael C.

Abstract

Acute care surgeons are uniquely aware of the importance of systemic inflammatory response and its influence on postoperative outcomes; concepts like damage control have evolved from this experience. For surgeons whose practice is mostly elective, the significance of such systemic inflammation may be underappreciated. This study sought to determine the influence of preoperative systemic inflammation on postoperative outcome in patients requiring emergent colon surgery.

Published
2012
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48. Innate Immune Response to Pulmonary Contusion

Author

Hoth, J. Jason, Wells, Jonathan D., Yoza, Barbara K., and McCall, Charles E.

Abstract

Lung injury from pulmonary contusion is a common traumatic injury, predominantly seen after blunt chest trauma, such as in vehicular accidents. The local and systemic inflammatory response to injury includes activation of innate immune receptors, elaboration of a variety of inflammatory mediators, and recruitment of inflammatory cells to the injured lung. Using a mouse model of pulmonary contusion, we had previously shown that innate immune Toll-like receptors 2 and 4 (TLR2 and TLR4) mediate the inflammatory response to lung injury. In this study, we used chimeric mice generated by adoptive bone marrow transfer between TLR2--or TLR4--and wild-type mice. We found that, in the lung, both bone marrow–derived and nonmyeloid cells contribute to TLR-dependent inflammatory responses after injury in a cell type–specific manner. We also show a novel TLR2-dependent injury mechanism that is associated with enhanced airway epithelial cell apoptosis and increased pulmonary FasL and Fas expression in the lungs from injured mice. Thus, in addition to cardiopulmonary physiological dysfunction, cell type–specific TLR and their differential response to injury may provide novel specific targets for management of patients with pulmonary contusion.

Published
2012
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50. A Critical Assessment of Outcomes in Emergency versus Nonemergency General Surgery Using the American College of Surgeons National Surgical Quality Improvement Program Database

Author

Becher, Robert D., Hoth, J. Jason, Miller, Preston R., Mowery, Nathan T., Chang, Michael C., and Meredith, J. Wayne

Abstract

Emergent operations are thought to carry higher morbidity and mortality than nonemergent cases. However, there is a lack of specific outcomes data for emergent general surgery procedures. The objective of our study was to assess and quantify postoperative morbidity and mortality for emergency versusnonemergency general surgery operations. All general surgery inpatients were identified in the American College of Surgeons National Surgical Quality Improvement Program 2008 database. Preoperative, intraoperative, and postoperative clinical metrics and occurrences were assessed. A total of 25,770 emergent and 98,867 nonemergent cases were identified. Postoperative morbidity was significantly worse in the emergent group, including ventilation more than 48 hours, bleeding requiring transfusion, deep vein thrombosis, renal failure, and need for reoperation. Overall, emergent cases had significantly more postoperative complications (22.8% vs14.2%) and higher mortality rates (6.5% vs1.4%). General surgery patients who undergo emergent operations have significantly poorer outcomes when compared with nonemergent patients; our analysis has quantified these differences. Emergent patients seem to manifest unique clinical, pathophysiologic, and inflammatory responses to their surgical disease. This data suggests that there is a need for improvement in both methods and systems of care for the emergent population.

Published
2011
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