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1. Pain, Analgesic Use, and Patient Satisfaction With Spinal Versus General Anesthesia for Hip Fracture Surgery : A Randomized Clinical Trial

Author

Mark D, Neuman, Rui, Feng, Susan S, Ellenberg, Frederick, Sieber, Daniel I, Sessler, Jay, Magaziner, Nabil, Elkassabany, Eric S, Schwenk, Derek, Dillane, Edward R, Marcantonio, Diane, Menio, Sabry, Ayad, Manal, Hassan, Trevor, Stone, Steven, Papp, Derek, Donegan, Mitchell, Marshall, J Douglas, Jaffe, Charles, Luke, Balram, Sharma, Syed, Azim, Robert, Hymes, Ki-Jinn, Chin, Richard, Sheppard, Barry, Perlman, Joshua, Sappenfield, Ellen, Hauck, Mark A, Hoeft, Ann, Tierney, Lakisha J, Gaskins, Annamarie D, Horan, Trina, Brown, James, Dattilo, Jeffrey L, Carson, Thomas, Looke, Sandra, Bent, Ariana, Franco-Mora, Pamela, Hedrick, Matthew, Newbern, Rafik, Tadros, Karen, Pealer, Kamen, Vlassakov, Carolyn, Buckley, Lauren, Gavin, Svetlana, Gorbatov, James, Gosnell, Talora, Steen, Avery, Vafai, Jose, Zeballos, Jennifer, Hruslinski, Louis, Cardenas, Ashley, Berry, John, Getchell, Nicholas, Quercetti, Gauasan, Bajracharya, Damien, Billow, Michael, Bloomfield, Evis, Cuko, Mehrun K, Elyaderani, Robert, Hampton, Hooman, Honar, Dilara, Khoshknabi, Daniel, Kim, David, Krahe, Michael M, Lew, Conjeevram B, Maheshwer, Azfar, Niazi, Partha, Saha, Ahmed, Salih, Robert J, de Swart, Andrew, Volio, Kelly, Bolkus, Matthew, DeAngelis, Gregory, Dodson, Jeffrey, Gerritsen, Brian, McEniry, Ludmil, Mitrev, M Kwesi, Kwofie, Anne, Belliveau, Flynn, Bonazza, Vera, Lloyd, Izabela, Panek, Jared, Dabiri, Chris, Chavez, Jason, Craig, Todd, Davidson, Chad, Dietrichs, Cheryl, Fleetwood, Mike, Foley, Chris, Getto, Susie, Hailes, Sarah, Hermes, Andy, Hooper, Greg, Koener, Kate, Kohls, Leslie, Law, Adam, Lipp, Allison, Losey, William, Nelson, Mario, Nieto, Pam, Rogers, Steve, Rutman, Garrett, Scales, Barbara, Sebastian, Tom, Stanciu, Gregg, Lobel, Michelle, Giampiccolo, Dara, Herman, Margit, Kaufman, Bryan, Murphy, Clara, Pau, Thomas, Puzio, Marlene, Veselsky, Kelly, Apostle, Dory, Boyer, Brenda Chen, Fan, Susan, Lee, Mike, Lemke, Richard, Merchant, Farhad, Moola, Kyrsten, Payne, Bertrand, Perey, Darius, Viskontas, Mark, Poler, Patricia, D'Antonio, Greg, O'Neill, Amer, Abdullah, Jamie, Fish-Fuhrmann, Mark, Giska, Christina, Fidkowski, Stuart Trent, Guthrie, William, Hakeos, Lillian, Hayes, Joseph, Hoegler, Katherine, Nowak, Jeffery, Beck, Jaslynn, Cuff, Greg, Gaski, Sharon, Haaser, Michael, Holzman, A Stephen, Malekzadeh, Lolita, Ramsey, Jeff, Schulman, Cary, Schwartzbach, Tangwan, Azefor, Arman, Davani, Mahmood, Jaberi, Courtney, Masear, Syed Basit, Haider, Carolyn, Chungu, Ali, Ebrahimi, Karim, Fikry, Andrew, Marcantonio, Anitha, Shelvan, David, Sanders, Collin, Clarke, Abdel, Lawendy, Gary, Schwartz, Mohit, Garg, Joseph, Kim, Juan, Caruci, Ekow, Commeh, Randy, Cuevas, Germaine, Cuff, Lola, Franco, David, Furgiuele, Matthew, Giuca, Melissa, Allman, Omid, Barzideh, James, Cossaro, Armando, D'Arduini, Anita, Farhi, Jason, Gould, John, Kafel, Anuj, Patel, Abraham, Peller, Hadas, Reshef, Mohammed, Safur, Fiore, Toscano, Tiffany, Tedore, Michael, Akerman, Eric, Brumberger, Sunday, Clark, Rachel, Friedlander, Anita, Jegarl, Joseph, Lane, John P, Lyden, Nili, Mehta, Matthew T, Murrell, Nathan, Painter, William, Ricci, Kaitlyn, Sbrollini, Rahul, Sharma, Peter A D, Steel, Michele, Steinkamp, Roniel, Weinberg, David Stephenson, Wellman, Antoun, Nader, Paul, Fitzgerald, Michaela, Ritz, Greg, Bryson, Alexandra, Craig, Cassandra, Farhat, Braden, Gammon, Wade, Gofton, Nicole, Harris, Karl, Lalonde, Allan, Liew, Bradley, Meulenkamp, Kendra, Sonnenburg, Eugene, Wai, Geoffrey, Wilkin, Karen, Troxell, Mary Ellen, Alderfer, Jason, Brannen, Christopher, Cupitt, Stacy, Gerhart, Renee, McLin, Julie, Sheidy, Katherine, Yurick, Fei, Chen, Karen, Dragert, Geza, Kiss, Halina, Malveaux, Deborah, McCloskey, Scott, Mellender, Sagar S, Mungekar, Helaine, Noveck, Carlos, Sagebien, Luat, Biby, Gail, McKelvy, Anna, Richards, Ramon, Abola, Brittney, Ayala, Darcy, Halper, Ana, Mavarez, Sabeen, Rizwan, Stephen, Choi, Imad, Awad, Brendan, Flynn, Patrick, Henry, Richard, Jenkinson, Lilia, Kaustov, Elizabeth, Lappin, Paul, McHardy, Amara, Singh, Joanne, Donnelly, Meera, Gonzalez, Christopher, Haydel, Jon, Livelsberger, Theresa, Pazionis, Bridget, Slattery, Maritza, Vazquez-Trejo, Jaime, Baratta, Michael, Cirullo, Brittany, Deiling, Laura, Deschamps, Michael, Glick, Daniel, Katz, James, Krieg, Jennifer, Lessin, Jeffrey, Mojica, Marc, Torjman, Rongyu, Jin, Mary Jane, Salpeter, Mark, Powell, Jeffrey, Simmons, Prentiss, Lawson, Promil, Kukreja, Shanna, Graves, Adam, Sturdivant, Ayesha, Bryant, Sandra Joyce, Crump, Michelle, Verrier, James, Green, Matthew, Menon, Richard, Applegate, Ana, Arias, Natasha, Pineiro, Jeffrey, Uppington, Phillip, Wolinsky, Amy, Gunnett, Jennifer, Hagen, Sara, Harris, Kevin, Hollen, Brian, Holloway, Mary Beth, Horodyski, Trevor, Pogue, Ramachandran, Ramani, Cameron, Smith, Anna, Woods, Matthew, Warrick, Kelly, Flynn, Paul, Mongan, Yatish, Ranganath, Sean, Fernholz, Esperanza, Ingersoll-Weng, Anil, Marian, Melinda, Seering, Zita, Sibenaller, Lori, Stout, Allison, Wagner, Alicia, Walter, Cynthia, Wong, Denise, Orwig, Maithri, Goud, Chris, Helker, Lydia, Mezenghie, Brittany, Montgomery, Peter, Preston, J Sanford, Schwartz, Ramona, Weber, Lee A, Fleisher, Samir, Mehta, Alisa J, Stephens-Shields, Cassandra, Dinh, Jacques E, Chelly, Shiv, Goel, Wende, Goncz, Touichi, Kawabe, Sharad, Khetarpal, Amy, Monroe, Vladislav, Shick, Max, Breidenstein, Timothy, Dominick, Alexander, Friend, Donald, Mathews, Richard, Lennertz, Robert, Sanders, Helen, Akere, Tyler, Balweg, Amber, Bo, Christopher, Doro, David, Goodspeed, Gerald, Lang, Maggie, Parker, Amy, Rettammel, Mary, Roth, Marissa, White, Paul, Whiting, Brian F S, Allen, Tracie, Baker, Debra, Craven, Matt, McEvoy, Teresa, Turnbo, Stephen, Kates, Melanie, Morgan, Teresa, Willoughby, Wade, Weigel, David, Auyong, Ellie, Fox, Tina, Welsh, Bruce, Cusson, Sean, Dobson, Christopher, Edwards, Lynette, Harris, Daryl, Henshaw, Kathleen, Johnson, Glen, McKinney, Scott, Miller, Jon, Reynolds, B Scott, Segal, Jimmy, Turner, David, VanEenenaam, Robert, Weller, Jineli, Lei, Miriam, Treggiari, Shamsuddin, Akhtar, Marcelle, Blessing, Chanel, Johnson, Michael, Kampp, Kimberly, Kunze, Mary, O'Connor, Jinlei, Li, Duminda N, Wijeysundera, Sachin, Kheterpal, Reneé H, Moore, Alexander K, Smith, Laura L, Tosi, Lee, Fleisher, Christine, Langlois, Samuel, Oduwole, and Thomas, Rose

Subjects
Male, Analgesics, Canada, Pain, Postoperative, Hip Fractures, Pain, General Medicine, Anesthesia, General, Anesthesia, Spinal, Patient Satisfaction, Internal Medicine, Humans, Female, Aged
Abstract

The REGAIN (Regional versus General Anesthesia for Promoting Independence after Hip Fracture) trial found similar ambulation and survival at 60 days with spinal versus general anesthesia for hip fracture surgery. Trial outcomes evaluating pain, prescription analgesic use, and patient satisfaction have not yet been reported.To compare pain, analgesic use, and satisfaction after hip fracture surgery with spinal versus general anesthesia.Preplanned secondary analysis of a pragmatic randomized trial. (ClinicalTrials.gov: NCT02507505).46 U.S. and Canadian hospitals.Patients aged 50 years or older undergoing hip fracture surgery.Spinal or general anesthesia.Pain on postoperative days 1 through 3; 60-, 180-, and 365-day pain and prescription analgesic use; and satisfaction with care.A total of 1600 patients were enrolled. The average age was 78 years, and 77% were women. A total of 73.5% (1050 of 1428) of patients reported severe pain during the first 24 hours after surgery. Worst pain over the first 24 hours after surgery was greater with spinal anesthesia (rated from 0 [no pain] to 10 [worst pain imaginable]; mean difference, 0.40 [95% CI, 0.12 to 0.68]). Pain did not differ across groups at other time points. Prescription analgesic use at 60 days occurred in 25% (141 of 563) and 18.8% (108 of 574) of patients assigned to spinal and general anesthesia, respectively (relative risk, 1.33 [CI, 1.06 to 1.65]). Satisfaction was similar across groups.Missing outcome data and multiple outcomes assessed.Severe pain is common after hip fracture. Spinal anesthesia was associated with more pain in the first 24 hours after surgery and more prescription analgesic use at 60 days compared with general anesthesia.Patient-Centered Outcomes Research Institute

Published
2022

2. Apnea in Beach-Chair Position Status Post Interscalene Block: A Simulation Case for Anesthesia Residents

Author

Tyler Voigt, Allison Wagner, Clark Obr, and Tejinder Swaran Singh

Subjects
Anesthesia, Chronic Obstructive Pulmonary Disease, Regional Anesthesia, Intraoperative Apnea, Difficult Airway Algorithm, Cerebral Perfusion Pressure, Medicine (General), R5-920, Education
Abstract

Abstract Introduction Regional anesthesia is commonly performed for orthopedic operations, especially in situations when general anesthesia is preferably avoided. Anesthesia residents should understand the complications of regional procedures and should know how to treat them if treatment is warranted. This simulation involves a 60-year-old man who became apneic in the beach-chair position following an interscalene block for rotator cuff repair. It presents trainees with the opportunity to further their learning with regard to perioperative management and associated complications of patients receiving brachial plexus blocks. Methods This simulation is designed to be delivered in a single, 1-hour session. Materials contained within this simulation include a case template, a checklist of critical actions, a brief summary for key takeaways, and an evaluation form. At the conclusion of this simulation and debriefing session, the learner has had the opportunity to demonstrate progress in several of the anesthesiology milestones outlined by the Accreditation Council for Graduate Medical Education and the American Board of Anesthesiology in the Anesthesiology Milestone Project as they relate to this particular clinical topic. Results At the time of this submission, a total of 15 junior residents had completed this simulation. Commonly missed critical actions included difficulty of management of analgesia in a block that is not complete and correlation between noninvasive blood pressure on the arm and cerebral perfusion pressure. Learners’ comments were generally positive, indicating the residents felt this simulation was a worthwhile learning experience. Discussion The majority of anesthesia residents who have participated in this simulation were able to properly address apnea in the beach-chair position following a brachial plexus block. It is expected that this simulation will be performed approximately 15–20 times annually.

Published
2016
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4. The splicing factor SRSF6 controls Mycobacterium tuberculosis replication through its role in maintaining mitochondrial homeostasis

Author

Allison Wagner, Chi Weindel, Kelsi West, Robert Watson, and Kristin Patrick

Subjects
Immunology, Immunology and Allergy
Abstract

Macrophages are the primary host cell that supports the survival and replication of the intracellular bacterial pathogen Mycobacterium tuberculosis (Mtb). We are interested in how macrophage proteins are functionalized during Mtb infection. Global proteomics analysis of Mtb-infected primary macrophages found that many RNA binding proteins of the Serine/Arginine rich splicing family (SRSF) can be differentially phosphorylated, suggesting that these factors regulate splicing decisions during Mtb infection. Knockdown of one such SRSF protein, called SR6, results in basal upregulation of interferon stimulated genes (ISGs) in macrophages. We hypothesized that this phenotype was driven by mitochondrial damage that leaks mitochondria DNA into the cytosol and activates cGAS. Consistent with this idea, we measured increased mitochondrial stress and increased cell death in SR6 KD macrophages. Transcriptomics analysis of these cells revealed upregulation of an alternatively spliced (AS) isoform of the apoptotic factor BAX, which contributes to mitochondrial dysfunction, mtDNA release, and basal ISG expression. While BAX isoforms are known to regulate cell death, this is the first report of BAX AS regulating the type I IFN response. Lastly, we found that SR6 KD macrophages are permissive to Mtb replication, suggesting that controlling cell death at the level of BAX isoform abundance is an important but unappreciated component of the macrophage antibacterial repertoire. Together, our data support a model whereby SR6-dependent AS of Bax triggers mitochondria stress causing mtDNA leakage and type I IFN expression, metabolic dysfunction that primes cells to undergo cell death, and increased susceptibility to Mtb infection.

Published
2022

6. Study of properties of systems with topological order

Author

Teixeira, Allison Wagner, Santos, Vagson Luiz de Carvalho, and Fonseca, Jakson Miranda

Subjects
Supercondutividade, Magnetismo, Topologia, Física da Matéria Condensada
Abstract

Nesse trabalho, estudamos sistemas supercondutores e magnéticos, ambos com orde- namento topológico não trivial. Supercondutores topológicos apresentam condições para emergência de férmions de Majorana, cujo potencial efetivo foi calculado. Com tal potencial, algumas caracterı́sticas dos sistemas foram encontradas, como número de partı́culas, a equação de gap supercondutor e as condições em que supercondutivi- dade é induzida em isolantes topológicos por efeito de proximidade. A possibilidade de emergência de férmions de Majorana em cupratos supercondutores de alta tem- peratura crı́tica também foi estudada. Além disso, a massa de um skyrmion em uma rede de spin com topologia não trivial, em função da velocidade foi encontrada. Nesse caso, encontramos ainda uma transição de fase topológica devido ao aumento do número de skyrmions que ocorre acima de uma velocidade crı́tica. Por fim, de- terminamos estados de configurações magnéticas que minimizam a energia em uma nanocasca toroidal, que apresenta geometria com topologia não trivial. A partir do cálculo de energia de distintas configurações da magnetização pudemos construir um diagrama de estados. Palavras-Chave: Topologia. Supercondutividade. Magnetismo. In this work we studied superconductor and magnetic systems that have non trivial topological order. Topological superconductors present conditions to the emergence of Majorana fermions, whose the effective potential was calculated. With this po- tential, some characteristics of these systems were obtained, as the particle number, superconductor gap equation and the conditions of induced superconductivity in to- pological insulators by proximity effect. The possibility of emergency of Majorana fermions in High-T c cuprates was studied as well. Besides, the mass of a skyrmion in a spin lattice with non-trivial topology, as a function of the velocity, was obtai- ned. In this case, we found a topological phase transition due the increase of the number of skyrmions that occur above a critical velocity. Finally, we studied states of magnetic configurations that minimizes the energy of a toroidal nanoshell, which geometry has non trivial topology. From the calculus of the energies for distinct magnetization configurations we obtained a diagram of states. Keywords: Topology. Superconductivity. Magnetism.

Published
2020

7. Engaging patients as partners in a multicentre trial of spinal versus general anaesthesia for older adults

Author

Jennifer Hruslinski, Diane A. Menio, Robert A. Hymes, J. Douglas Jaffe, Christine Langlois, Lolita Ramsey, Lakisha J. Gaskins, Mark D. Neuman, Thomas Looke, Sandra Bent, Ariana Franco-Mora, Pamela Hedrick, Matthew Newbern, Rafik Tadros, Karen Pealer, Edward Marcantonio, Kamen Vlassakov, Carolyn Buckley, Svetlana Gorbatov, James Gosnell, Talora Steen, Avery Vafai, Jose Zeballos, Louis Cardenas, Ashley Berry, John Getchell, Nicholas Quercetti, Daniel I. Sessler, Sabry Ayad, Manal Hassan, Assad Ali, Gauasan Bajracharya, Damien Billow, Michael Bloomfield, Kavita Elliott, Robert Hampton, Linda He, Hooman Honar, Dilara Khoshknabi, Daniel Kim, Paul Minko, Adam Morris, Azfar Niazi, Tara Nutcharoen, Jeffrey Roberts, Partha Saha, Ahmed Salih, Alexis Skolaris, Taylor Stang, Victor Strimbu, Jesse Templeton, Andrew Volio, Jiayi Wang, Kelly Bolkus, Matthew DeAngelis, Gregory Dodson, Jeffrey Gerritsen, Brian McEniry, Ludmil Mitrev, Kwesi Kwofie, Flynn Bonazza, Vera Lloyd, Izabela Panek, Jared Dabiri, Chris Chavez, Jason Craig, Todd Davidson, Chad Dietrichs, Cheryl Fleetwood, Mike Foley, Chris Getto, Susie Hailes, Sarah Hermes, Andy Hooper, Greg Koener, Kate Kohls, Leslie Law, Adam Lipp, Allison Losey, William Nelson, Mario Nieto, Pam Rogers, Steve Rutman, Garrett Scales, Barbara Sebastian, Tom Stanciu, Gregg Lobel, Michelle Giampiccolo, Dara Herman, Margit Kaufman, Bryan Murphy, Clara Pau, Thomas Puzio, Marlene Veselsky, Trevor Stone, Kelly Apostle, Dory Boyer, Brenda Chen Fan, Susan Lee, Mike Lemke, Richard Merchant, Farhad Moola, Kyrsten Payne, Bertrand Perey, Darius Viskontas, Mark Poler, Patricia D'Antonio, Richard Sheppard, Amer Abdullah, Jamie Fish-Fuhrmann, Mark Giska, Christina Fidkowski, Trent Guthrie, William Hakeos, Lillian Hayes, Joseph Hoegler, Katherine Nowak, Robert Hymes, Jeffery Beck, Jaslynn Cuff, Greg Gaski, Sharon Haaser, Michael Holzman, A. Stephen Malekzadeh, Jeff Schulman, Cary Schwartzbach, Frederick Sieber, Tangwan Azefor, Charles Brown, Arman Davani, Mahmood Jaberi, Courtney Masear, Balram Sharma, Syed Basit Haider, Carolyn Chungu, Ali Ebrahimi, Karim Fikry, Kerri Gannon, Andrew Marcantonio, Meredith Pace, David Sanders, Collin Clarke, Abdel Lawendy, Gary Schwartz, Mohit Garg, Joseph Kim, Mitchell Marshall, Juan Caurci, Ekow Commeh, Randy Cuevas, Germaine Cuff, Lola Franco, David Furguiele, Matthew Giuca, Melissa Allman, Omid Barzideh, James Cossaro, Armando D'Arduini, Anita Farhi, Jason Gould, John Kafel, Anuj Patel, Abraham Peller, Hadas Reshef, Mohammed Safur, Fiore Toscano, Tiffany Tedore, Michael Akerman, Eric Brumberger, Sunday Clark, Rachel Friedlander, Anita Jegarl, Joseph Lane, John P. Lyden, Nili Mehta, Matthew T. Murrell, Nathan Painter, William Ricci, Kaitlyn Sbrollini, Rahul Sharma, Peter A.D. Steel, Michele Steinkamp, Roniel Weinberg, David Stephenson Wellman, Antoun Nader, Paul Fitzgerald, Michaela Ritz, Steven Papp, Greg Bryson, Alexandra Craig, Cassandra Farhat, Braden Gammon, Wade Gofton, Nicole Harris, Karl Lalonde, Allan Liew, Bradley Meulenkamp, Kendra Sonnenburg, Eugene Wai, Geoffrey Wilkin, Derek Donegan, Cassandra Dinh, Nabil Elkassabany, Annamarie Horan, Samir Mehta, Karen Troxell, Mary Ellen Alderfer, Jason Brannen, Christopher Cupitt, Stacy Gerhart, Renee McLin, Julie Sheidy, Katherine Yurick, Jeffrey Carson, Fei Chen, Karen Dragert, Geza Kiss, Halina Malveaux, Deborah McCloskey, Scott Mellender, Sagar S. Mungekar, Helaine Noveck, Carlos Sagebien, Barry Perlman, Luat Biby, Gail McKelvy, Anna Richards, Syed Azim, Ramon Abola, Brittney Ayala, Darcy Halper, Ana Mavarez, Stephen Choi, Imad Awad, Brendan Flynn, Patrick Henry, Richard Jenkinson, Lilia Kaustov, Elizabeth Lappin, Paul McHardy, Amara Singh, Ellen Hauck, Joanne Donnelly, Meera Gonzalez, Christopher Haydel, Jon Livelsberger, Theresa Pazionis, Bridget Slattery, Maritza Vazquez-Trejo, Eric Schwenk, Jaime Baratta, Brittany Deiling, Laura Deschamps, Michael Glick, Daniel Katz, James Krieg, Jennifer Lessin, Marc Torjman, Ki Jinn Chin, Rongyu Jin, Mary Jane Salpeter, Mark Powell, Jeffrey Simmons, Prentiss Lawson, Promil Kukreja, Shanna Graves, Adam Sturdivant, Ayesha Bryant, Sandra Joyce Crump, Derek Dillane, Michael Taylor, Michelle Verrier, Richard Applegate, Ana Arias, Natasha Pineiro, Jeffrey Uppington, Phillip Wolinsky, Joshua Sappenfield, Amy Gunnett, Jennifer Hagen, Sara Harris, Kevin Hollen, Brian Holloway, Mary Beth Horodyski, Trevor Pogue, Ramachandran Ramani, Cameron Smith, Anna Woods, Matthew Warrick, Kelly Flynn, Paul Mongan, Yatish Ranganath, Sean Fernholz, Esperanza Ingersoll-Weng, Anil Marian, Melinda Seering, Zita Sibenaller, Lori Stout, Allison Wagner, Alicia Walter, Cynthia Wong, Jay Magaziner, Denise Orwig, Trina Brown, Jim Dattilo, Susan Ellenberg, Rui Feng, Lee Fleisher, Lakisha Gaskins, Maithri Goud, Chris Helker, Lydia Mezenghie, Brittany Montgomery, Peter Preston, Alisa Stephens, J. Sanford Schwartz, Ann Tierney, Ramona Weber, Jacques Chelly, Shiv Goel, Wende Goncz, Touichi Kawabe, Sharad Khetarpal, Kevin King, Frank Kunkel, Charles Luke, Amy Monroe, Vladislav Shick, Anthony Silipo, Caroline Stehle, Katherine Szabo, Sudhakar Yennam, Mark Hoeft, Max Breidenstein, Timothy Dominick, Alexander Friend, Donald Mathews, Richard Lennertz, Helen Akere, Tyler Balweg, Amber Bo, Christopher Doro, David Goodspeed, Gerald Lang, Maggie Parker, Amy Rettammel, Mary Roth, Robert Sanders, Marissa White, Paul Whiting, Brian Allen, Tracie Baker, Debra Craven, Matt McEvoy, Teresa Turnbo, Stephen Kates, Melanie Morgan, Teresa Willoughby, Wade Weigel, David Auyong, Ellie Fox, Tina Welsh, Bruce Cusson, Sean Dobson, Christopher Edwards, Lynette Harris, Daryl Henshaw, Kathleen Johnson, Glen McKinney, Scott Miller, Jon Reynolds, Jimmy Turner, David VanEenenaam, Robert Weller, Shamsuddin Akhtar, Marcelle Blessing, Chanel Johnson, Michael Kampp, Kimberly Kunze, Jinlei Li, Mary O'Connor, and Miriam Treggiari

Subjects
medicine.medical_specialty, Canada, Research Subjects, Patient engagement, Hip fracture surgery, Patient Advocacy, Anesthesia, General, Patient advocacy, Anesthesia, Spinal, 03 medical and health sciences, 0302 clinical medicine, Nursing, 030202 anesthesiology, Fracture Fixation, Medicine, Humans, General anaesthesia, Cooperative Behavior, Geriatrics, Hip fracture, business.industry, Hip Fractures, Lived experience, Age Factors, Research process, medicine.disease, United States, Anesthesiology and Pain Medicine, Research Design, Patient Participation, business, Decision Making, Shared
Abstract

Summary Engaging patients—defined broadly as individuals with lived experience of a given condition, family members, caregivers, and the organisations that represent them—as partners in research is a priority for policymakers, funders, and the public. Nonetheless, formal efforts to engage patients are absent from most studies, and models to support meaningful patient engagement in clinical anaesthesia research have not been previously described. Here, we review our experience in developing and implementing a multifaceted patient engagement strategy within the Regional Versus General Anesthesia for Promoting Independence After Hip Fracture (REGAIN) surgery trial, an ongoing randomised trial comparing spinal vs general anaesthesia for hip fracture surgery in 1600 older adults across 45 hospitals in the USA and Canada. This strategy engaged patients and their representatives at both the level of overall trial oversight and at the level of individual recruiting sites. Activities spanned a continuum ranging from events designed to elicit patients' input on key decisions to longitudinal collaborations that empowered patients to actively participate in decision-making related to trial design and management. Engagement activities were highly acceptable to participants and led to concrete changes in the design and conduct of the REGAIN trial. The REGAIN experience offers a model for future efforts to engage patients as partners in clinical anaesthesia research, and highlights potential opportunities for investigators to increase the relevance of anaesthesia studies by incorporating patient voices and perspectives into the research process.

Published
2020

8. Alternative splicing of Bax controls cell death and innate immune responses in macrophages

Author

Allison Wagner, Chi Weindel, Robert Watson, and Kristin Patrick

Subjects
Immunology, Immunology and Allergy
Abstract

To defend against invading pathogens, the macrophage innate immune response requires rapid, robust gene expression reprogramming. Innate immune genes that are induced as part of this response are regulated at many steps. While transcriptional activation of innate immune genes has been extensively studied, the mechanisms driving their post-transcriptional regulation (i.e. alternative splicing) needs further investigation. To begin learning how pre-mRNA splicing changes impact the innate immune response in macrophages, we examined how loss of a splicing regulatory protein called SRSF6 (serine arginine rich splicing factor 6) impacts gene expression. We discovered a novel phenotype whereby loss of SRSF6 increased basal expression of many interferon stimulated genes (ISGs). Consistent with mitochondrial dysfunction, a phenotype that we and others have previously associated high basal ISG expression, we measured an increase in apoptosis and macrophage depolarization in SRSF6 knockdown macrophages compared to scramble controls. Subsequent bioinformatic analysis of RNA-seq data from SRSF6 knockdown macrophages identified an alternative splicing event in the apoptosis activation factor BAX. While Bax isoforms have previously been linked to cell death regulation, no one has reported a role for Bax isoforms in modulating mtDNA-driven innate immune responses. Our data is consistent with a model whereby upregulation of a Bax isoform promotes pore formation in mitochondria which 1) causes leakage of mtDNA into the cytosol where it is detected by cGAS, eliciting type I interferon production and 2) primes macrophages to undergo programmed cell death.

Published
2021

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