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1. Pancreaticoduodenectomy in trauma patients with grade IV–V duodenal or pancreatic injuries: a post hoc analysis of an EAST multicenter trial

Author

Jeffry Nahmias, Daniel N Holena, Bellal Joseph, Martin Schreiber, Lisa M Kodadek, Mayur Narayan, Grace Chang, Joe Patton, Abid Khan, Mark Seamon, Jessica H Beard, Michelle T Bover Manderski, Michael A Vella, Ryan Peter Dumas, Haytham Kaafarani, Alison A Smith, Rachel Leah Choron, Christopher Bargoud, Amanda L Teichman, Francesk Mulita, Christine T Trankiem, Hashim Ahmed, Aaron Anderson, Odessa Pulido, Caleb Mentzer, Jane Keating, Mira Ghneim, Reynold Henry, Dane R Scantling, Andrew Benjamin, Christopher W Foote, Carlos H Palacio, Randi N Smith, Meghan Jonikas, Dias Argandykov, Jason D Sciarretta, Joshua P Hazelton, Pascal Udekwu, Jordan Michael Kirsch, Charoo Piplani, Julia Kuzinar, Dustin Hanos, Iman N Afif, Navpreet Kaur Dhillon, Ashling Zhang, Rebekah Devasahayam, Oliver Gunter, Brandi Sun, Chloe S Cao, Jessica K Reynolds, Lauren A Hilt, Karla Echeverria-Rosario, Nathaniel S Fung, Caitlin A Fitzgerald, Jeremy H Levin, JaeHee Yoon, Jacqueline Blank, Christopher J McLaughlin, Rami Al-Aref, Daniel S Howard, Kate Dellonte, Brent Hopkins, Chloe Shell, Evan G Wong, Howard Lieberman, Walter A Ramsey, Collin H Stewart, Claudia Alvarez, John D Berne, Ivan Puente, Ilya Rakitin, Lindsey Perea, Jason Wade, Laura K Mann, Vasileios Mousafeiris, Shari Reid-Gruner, Erica Sais, and Lilamarie Moko

Subjects
Surgery, RD1-811, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Introduction The utility of pancreaticoduodenectomy (PD) for high-grade traumatic injuries remains unclear and data surrounding its use are limited. We hypothesized that PD does not result in improved outcomes when compared with non-PD surgical management of grade IV–V pancreaticoduodenal injuries.Methods This is a retrospective, multicenter analysis from 35 level 1 trauma centers from January 2010 to December 2020. Included patients were ≥15 years of age with the American Association for the Surgery of Trauma grade IV–V duodenal and/or pancreatic injuries. The study compared operative repair strategy: PD versus non-PD.Results The sample (n=95) was young (26 years), male (82%), with predominantly penetrating injuries (76%). There was no difference in demographics, hemodynamics, or blood product requirement on presentation between PD (n=32) vs non-PD (n=63). Anatomically, PD patients had more grade V duodenal, grade V pancreatic, ampullary, and pancreatic ductal injuries compared with non-PD patients (all p

Published
2024
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2. Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Author

Gennaro Perrone, Mario Giuffrida, Fikri Abu-Zidan, Vitor F. Kruger, Marco Livrini, Gabriele Luciano Petracca, Giorgio Rossi, Antonio Tarasconi, Brian W. C. A. Tian, Elena Bonati, Ricardo Mentz, Federico N. Mazzini, Juan P. Campana, Elisabeth Gasser, Reinhold Kafka-Ritsch, Daniel M. Felsenreich, Christopher Dawoud, Stefan Riss, Carlos Augusto Gomes, Felipe Couto Gomes, Ricardo Alessandro Teixeira Gonzaga, Cassio Alfred Brattig Canton, Bruno Monteiro Pereira, Gustavo P. Fraga, Leticia Gonçalves Zem, Vinicius Cordeiro-Fonseca, Renato de Mesquita Tauil, Boyko Atanasov, Nikolay Belev, Nikola Kovachev, L. Juan José Meléndez, Ana Dimova, Stefan Dimov, Zdravko Zelić, Goran Augustin, Branko Bogdanić, Trpimir Morić, Elie Chouillard, Melinda Bajul, Belinda De Simone, Yves Panis, Francesco Esposito, Margherita Notarnicola, Lelde Lauka, Anna Fabbri, Hassen Hentati, Iskander Fnaiech, Venara Aurélien, Marie Bougard, Maxime Roulet, Zaza Demetrashvili, Irakli Pipia, Giorgi Merabishvili, Konstantinos Bouliaris, Georgios Koukoulis, Christos Doudakmanis, Sofia Xenaki, Emmanuel Chrysos, Stamatios Kokkinakis, Panteleimon Vassiliu, Nikolaos Michalopoulos, Ioannis Margaris, Aristotelis Kechagias, Konstantinos Avgerinos, Jevgeni Katunin, Eftychios Lostoridis, Eleni-Aikaterini Nagorni, Antonio Pujante, Francesk Mulita, Ioannis Maroulis, Michail Vailas, Athanasios Marinis, Ioannis Siannis, Eirini Bourbouteli, Dimitrios K. Manatakis, Nikolaos Tasis, Vasileios Acheimastos, Sotiropoulou Maria, Kapiris Stylianos, Harilaos Kuzeridis, Dimitrios Korkolis, Evangelos Fradelos, George Kavalieratos, Thalia Petropoulou, Andreas Polydorou, Ioannis Papacostantinou, Tania Triantafyllou, Despina Kimpizi, Dimitrios Theodorou, Konstantinos Toutouzas, Alexandros Chamzin, Maximos Frountzas, Dimitrios Schizas, Ioannis Karavokyros, Athanasios Syllaios, Alexandros Charalabopoulos, Maria Boura, Efstratia Baili, Orestis Ioannidis, Lydia Loutzidou, Elissavet Anestiadou, Ioannis Tsouknidas, Georgios Petrakis, Eleni Polenta, Lovenish Bains, Rahul Gupta, Sudhir K. Singh, Archana Khanduri, Miklosh Bala, Asaf Kedar, Marcello Pisano, Mauro Podda, Adolfo Pisanu, Gennaro Martines, Giuseppe Trigiante, Giuliano Lantone, Antonino Agrusa, Giuseppe Di Buono, Salvatore Buscemi, Massimiliano Veroux, Rossella Gioco, Gastone Veroux, Luigi Oragano, Sandro Zonta, Federico Lovisetto, Carlo V. Feo, Antonio Pesce, Nicolò Fabbri, Giulio Lantone, Fabio Marino, Fabrizio Perrone, Leonardo Vincenti, Vincenzo Papagni, Arcangelo Picciariello, Stefano Rossi, Biagio Picardi, Simone Rossi Del Monte, Diego Visconti, Giulia Osella, Luca Petruzzelli, Giusto Pignata, Jacopo Andreuccetti, Rossella D’Alessio, Massimo Buonfantino, Eleonora Guaitoli, Stefano Spinelli, Gianluca Matteo Sampietro, Carlo Corbellini, Leonardo Lorusso, Alice Frontali, Isabella Pezzoli, Alessandro Bonomi, Andrea Chierici, Christian Cotsoglou, Giuseppe Manca, Antonella Delvecchio, Nicola Musa, Massimiliano Casati, Laface Letizia, Emmanuele Abate, Giorgio Ercolani, Fabrizio D’Acapito, Leonardo Solaini, Gianluca Guercioni, Simone Cicconi, Diego Sasia, Felice Borghi, Giorgio Giraudo, Giuseppe Sena, Pasquale Castaldo, Eugenia Cardamone, Giuseppe Portale, Matteo Zuin, Ylenia Spolverato, Marialusia Esposito, Roberta Maria Isernia, Maria Di Salvo, Romina Manunza, Giuseppe Esposito, Marcello Agus, Emanuele Luigi Giuseppe Asti, Daniele Tiziano Bernardi, Tommaso Panici Tonucci, Davide Luppi, Massimiliano Casadei, Stefano Bonilauri, Angela Pezzolla, Annunziata Panebianco, Rita Laforgia, Maurizio De Luca, Monica Zese, Dario Parini, Elio Jovine, Giuseppina De Sario, Raffaele Lombardi, Giovanni Aprea, Giuseppe Palomba, Marianna Capuano, Giulio Argenio, Gianluca Orio, Mariano Fortunato Armellino, Marina Troian, Martina Guerra, Carlo Nagliati, Alan Biloslavo, Paola Germani, Giada Aizza, Igor Monsellato, Ali Chaouki Chahrour, Gabriele Anania, Cristina Bombardini, Francesco Bagolini, Gabriele Sganga, Pietro Fransvea, Valentina Bianchi, Paolo Boati, Francesco Ferrara, Francesco Palmieri, Pasquale Cianci, Domenico Gattulli, Enrico Restini, Nicola Cillara, Alessandro Cannavera, Gabriela Elisa Nita, Jlenia Sarnari, Francesco Roscio, Federico Clerici, Ildo Scandroglio, Stefano Berti, Alessandro Cadeo, Alice Filippelli, Luigi Conti, Carmine Grassi, Gaetano Maria Cattaneo, Marina Pighin, Davide Papis, Giovanni Gambino, Vanessa Bertino, Domenico Schifano, Daniela Prando, Luisella Fogato, Fabio Cavallo, Luca Ansaloni, Roberto Picheo, Nicholas Pontarolo, Norma Depalma, Marcello Spampinato, Stefano D’Ugo, Luca Lepre, Michela Giulii Capponi, Rossella Domenica Campa, Giuliano Sarro, Vincenza Paola Dinuzzi, Stefano Olmi, Matteo Uccelli, Davide Ferrari, Marco Inama, Gianluigi Moretto, Michele Fontana, Francesco Favi, Erika Picariello, Alessia Rampini, Andrea Barberis, Antonio Azzinnaro, Alba Oliva, Luigi Totaro, Ilaria Benzoni, Valerio Ranieri, Gabriella Teresa Capolupo, Filippo Carannante, Marco Caricato, Maurizio Ronconi, Silvia Casiraghi, Giovanni Casole, Desire Pantalone, Giovanni Alemanno, Maximilian Scheiterle, Marco Ceresoli, Marco Cereda, Chiara Fumagalli, Federico Zanzi, Stefano Bolzon, Enrico Guerra, Francesca Lecchi, Paola Cellerino, Antonella Ardito, Rosa Scaramuzzo, Andrea Balla, Pasquale Lepiane, Nicola Tartaglia, Antonio Ambrosi, Giovanna Pavone, Gian Marco Palini, Simone Veneroni, Gianluca Garulli, Claudio Ricci, Beatrice Torre, Iris Shari Russo, Matteo Rottoli, Marta Tanzanu, Angela Belvedere, Marco Milone, Michele Manigrasso, Giovanni Domenico De Palma, Micaela Piccoli, Gianmaria Casoni Pattacini, Stefano Magnone, Paolo Bertoli, Michele Pisano, Paolo Massucco, Marco Palisi, Andrea-Pierre Luzzi, Francesco Fleres, Guglielmo Clarizia, Alessandro Spolini, Yoshiro Kobe, Takayuki Toma, Fumihiko Shimamura, Robert Parker, Sinkeet Ranketi, Mercy Mitei, Saulius Svagzdys, Henrikas Pauzas, Justas Zilinskas, Tomas Poskus, Marius Kryzauskas, Matas Jakubauskas, Andee Dzulkarnaen Zakaria, Zaidi Zakaria, Michael Pak-Kai Wong, Asri Che Jusoh, Muhammad Nazreen Zakaria, Daniel Rios Cruz, Aurea Barbara Rodriguez Elizalde, Alejandro Bañon Reynaud, Edgard Efren Lozada Hernandez, Jose maria Victor Palomo Monroy, Diego Hinojosa-Ugarte, Martha Quiodettis, María Esther Du Bois, José Latorraca, Piotr Major, Michał Pędziwiatr, Magdalena Pisarska-Adamczyk, Maciej Walędziak, Andrzej Kwiatkowski, Łukasz Czyżykowski, Silvia Dantas da Costa, Bela Pereira, Ana Rita Oliveira Ferreira, Filipe Almeida, Ricardo Rocha, Carla Carneiro, Diego Pita Perez, João Carvas, Catarina Rocha, Cátia Ferreira, Rita Marques, Urânia Fernandes, Pedro Leao, André Goulart, Rita Gonçalves Pereira, Sara Daniela Direito Patrocínio, Nuno Gonçalo Gonçalves de Mendonça, Maria Isabel Cerqueira Manso, Henrique Manuel Cardoso Morais, Paulo Sebastião Cardoso, Valentin Calu, Adrian Miron, Elena Adelina Toma, Mahir Gachabayov, Abakar Abdullaev, Andrey Litvin, Taras Nechay, Alexander Tyagunov, Anvar Yuldashev, Alison Bradley, Michael Wilson, Arpád Panyko, Zuzana Látečková, Vladimír Lacko, Dusan Lesko, Marek Soltes, Jozef Radonak, Victor Turrado-Rodriguez, Roser Termes-Serra, Xavier Morales-Sevillano, Pierfrancesco Lapolla, Andrea Mingoli, Gioia Brachini, Maurizio Degiuli, Silvia Sofia, Rossella Reddavid, Andrea de Manzoni Garberini, Angelica Buffone, Eduardo Perea del Pozo, Daniel Aparicio-Sánchez, Sandra Dos Barbeito, Mercedes Estaire-Gómez, Rebeca Vitón-Herrero, Mª de los Ángeles Gil Olarte-Marquez, José Gil-Martínez, Felipe Alconchel, Tatiana Nicolás-López, Aida Cristina Rahy-Martin, María Pelloni, Raquel Bañolas-Suarez, Fernando Mendoza-Moreno, Francisca García-Moreno Nisa, Manuel Díez-Alonso, María Elisa Valle Rodas, María Carmona Agundez, María Inmaculada Pérez Andrés, Claudia Cristina Lopes Moreira, Aintzane Lizarazu Perez, Iñigo Augusto Ponce, Ana María González-Castillo, Estela Membrilla-Fernández, Silvia Salvans, Mario Serradilla-Martín, Pablo Sancho Pardo, Daniel Rivera-Alonso, Jana Dziakova, Jose Mugüerza Huguet, Naila Pagès Valle, Enrique Colás Ruiz, Cristina Rey Valcárcel, Cristina Ruiz Moreno, Yeniffer Tatiana Moreno Salazar, Juan Jesús Rubio García, Silvia Sevila Micó, Joaquín Ruiz López, Silvia Pérez Farré, Maite Santamaria Gomez, Nuria Mestres Petit, Alberto Titos-García, Jose Manuel Aranda-Narváez, Laura Romacho-López, Luis Sánchez-Guillén, Veronica Aranaz-Ostariz, Marina Bosch-Ramírez, Aleix Martínez-Pérez, Elías Martínez-López, Juan Carlos Sebastián-Tomás, Granada Jimenez-Riera, Javier Jimenez-Vega, Jose Aurelio Navas Cuellar, Andrea Campos-Serra, Anna Muñoz-Campaña, Raquel Gràcia-Roman, Javier Martínez Alegre, Francisca Lima Pinto, Sara Nuñez O’Sullivan, Francisco Blanco Antona, Beatriz Muñoz Jiménez, Jaime López-Sánchez, Zahira Gómez Carmona, Rocio Torres Fernández, Isabel Blesa Sierra, Laura Román García de León, Verónica Polaino Moreno, Eva Iglesias, Paola Lora Cumplido, Altea Arango Bravo, Ignacio Rey Simó, Carlota López Domínguez, Aloia Guerreiro Caamaño, Rafael Calleja Lozano, Manuel Durán Martínez, Álvaro Naranjo Torres, Javier Tomas Morales Bernaldo de Quiros, Gianluca Pellino, Miriam Moratal Cloquell, Elsa García Moller, Sami Jalal-Eldin, Ahmed K. Abdoun, Hytham K. S. Hamid, Varut Lohsiriwat, Aitsariya Mongkhonsupphawan, Oussama Baraket, Karim Ayed, Imed Abbassi, Ali Ben Ali, Houssem Ammar, Ali Kchaou, Ahmed Tlili, Imen Zribi, Elif Colak, Suleyman Polat, Zehra Alan Koylu, Ali Guner, Mehmet Arif Usta, Murat Emre Reis, Baris Mantoglu, Emre Gonullu, Emrah Akin, Fatih Altintoprak, Zulfu Bayhan, Necattin Firat, Arda Isik, Ufuk Memis, Mehmet Bayrak, Yasemin Altıntaş, Yasin Kara, Mehmet Abdussamet Bozkurt, Ali Kocataş, Koray Das, Ahmet Seker, Nazmi Ozer, Semra Demirli Atici, Korhan Tuncer, Tayfun Kaya, Zeynep Ozkan, Onur Ilhan, Ibrahim Agackiran, Mustafa Yener Uzunoglu, Eren Demirbas, Yuksel Altinel, Serhat Meric, Nadir Adnan Hacım, Derya Salim Uymaz, Nail Omarov, Emre Balık, Giovanni D. Tebala, Hany Khalil, Mridul Rana, Mansoor Khan, Charlotte Florence, Christie Swaminathan, Cosimo Alex Leo, Lampros Liasis, Josef Watfah, Ivan Trostchansky, Edward Delgado, Marcelo Pontillo, Rifat Latifi, Raul Coimbra, Sara Edwards, Ana Lopez, George Velmahos, Ander Dorken, Anthony Gebran, Amanda Palmer, Jeffrey Oury, James M. Bardes, Sirivan Suon Seng, Lauren S. Coffua, Asanthi Ratnasekera, Tanya Egodage, Karla Echeverria-Rosario, Isabella Armento, Lena M. Napolitano, Naveen F. Sangji, Mark Hemmila, Jacob A. Quick, Tyler R. Austin, Theodore S. Hyman, William Curtiss, Amanda McClure, Nicholas Cairl, Walter L. Biffl, Hung P. Truong, Kathryn Schaffer, Summer Reames, Filippo Banchini, Patrizio Capelli, Federico Coccolini, Massimo Sartelli, Francesca Bravi, Carlo Vallicelli, Vanni Agnoletti, Gian Luca Baiocchi, and Fausto Catena

Subjects
Hartmann’s procedure, Ostomy, Emergency surgery, Resection, Primary anastomosis, Left side, Surgery, RD1-811, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann’s procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P

Published
2024
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3. Outcomes Among Trauma Patients with Duodenal Leak Following Primary vs Complex Repair of Duodenal Injuries: An EAST Multicenter Trial

Author

Rachel L. Choron, Amanda Teichman, Christopher Bargoud, Jason D. Sciarretta, Randi Smith, Dustin Hanos, Iman N. Afif, Jessica H. Beard, Navpreet K. Dhillon, Ashling Zhang, Mira Ghneim, Rebekah J. Devasahayam, Oliver L. Gunter, Alison A. Smith, Brandi Sun, Chloe S. Cao, Jessica K. Reynolds, Lauren A Hilt, Daniel N. Holena, Grace Chang, Meghan Jonikas, Karla Echeverria-Rosario, Nathaniel S. Fung, Aaron Anderson, Ryan P. Dumas, Caitlin A. Fitzgerald, Jeremy H. Levin, Christine T. Trankiem, JaeHee Yoon, Jacqueline Blank, Joshua P. Hazelton, Christopher J. McLaughlin, Rami Al-Aref, Jordan M. Kirsch, Daniel S. Howard, Dane R. Scantling, Kate Dellonte, Michael Vella, Brent Hopkins, Chloe Shell, Pascal O. Udekwu, Evan G Wong, Bellal Joseph, Howard Lieberman, Walter A Ramsey, Collin H. Stewart, Claudia Alvarez, John D. Berne, Jeffry Nahmias, Ivan Puente, Joe H. Patton, Ilya Rakitin, Lindsey Perea, Odessa Pulido, Hashim Ahmed, Jane Keating, Lisa M. Kodadek, Jason Wade, Reynold Henry, Martin A. Schreiber, Andrew J. Benjamin, Abid Khan, Laura K. Mann, Caleb J. Mentzer, Vasileios Mousafeiris, Francesk Mulita, Shari Reid-Gruner, Erica Sais, Christopher Foote, Carlos H Palacio, Dias Argandykov, Haytham Kaafarani, Susette Coyle, Marie Macor, Michelle T. Bover Manderski, Mayur Narayan, and Mark J. Seamon

Subjects
Surgery, Critical Care and Intensive Care Medicine
Published
2023
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4. Pediatric Trauma

Author

Stacey Staman, Nicole Fox, Karla Echeverria Rosario, and Lindsey L Perea

Subjects
Male, medicine.medical_specialty, MEDLINE, Aftercare, Injury Severity Score, Trauma Centers, Pain control, medicine, Humans, Prospective Studies, Child, Prospective survey, business.industry, Trauma center, General Medicine, medicine.disease, Patient Discharge, Pediatrics, Perinatology and Child Health, Emergency medicine, Behavioral medicine, Emergency Medicine, Wounds and Injuries, Anxiety, Female, medicine.symptom, business, Pediatric trauma
Abstract

OBJECTIVES Pediatric trauma patients are injured during crucial developmental years and require subsequent absence from school and activities. The impact of these changes on pediatric trauma patients is not well studied. We sought to assess the functional and emotional impact of pediatric trauma. In addition, the inpatient experience was evaluated for performance improvement purposes. METHODS A prospective survey was conducted at our trauma center (February 2019 to May 2019) of admitted trauma patients (

Published
2021
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5. Utilization of Natural Language Processing Software to Identify Worrisome Pancreatic Lesions

Author

Keshav Kooragayala, Connor Crudeli, Ami Kalola, Vipul Bhat, Johanna Lou, Richard Sensenig, Umur Atabek, Karla Echeverria, and Young Hong

Subjects
Adult, Pancreatic Neoplasms, Oncology, Humans, Surgery, Pancreatic Cyst, Software, Carcinoma, Pancreatic Ductal, Natural Language Processing, Retrospective Studies
Abstract

Computed tomography (CT) imaging is routinely obtained for diagnostics, especially in trauma and emergency rooms, often identifying incidental findings. We utilized a natural language processing (NLP) algorithm to quantify the incidence of clinically relevant pancreatic lesions in CT imaging.We utilized the electronic medical record to perform a retrospective chart review of adult patients admitted for trauma to a level 1 tertiary care center between 2010 and 2020 who underwent abdominal CT imaging. An open-source NLP software was used to identify patients with intrapapillary mucinous neoplasms (IPMN), pancreatic cysts, pancreatic ductal dilation, or pancreatic masses after optimizing the algorithm using a test group of patients who underwent pancreatic surgery.The algorithm identified pancreatic lesions in 27 of 28 patients who underwent pancreatic surgery and excluded 1 patient who had a pure ampullary mass. The study cohort consisted of 18,769 patients who met our inclusion criteria admitted to the hospital. Of this population, 232 were found to have pancreatic lesions of interest. There were 48 (20.7%) patients with concern for IPMN, pancreatic cysts in 36 (15.5%), concerning masses in 30 (12.9%), traumatic findings in 44 (19.0%), pancreatitis in 41 (17.7%), and ductal abnormalities in 19 (18.2%) patients. Prior pancreatic surgery and other findings were identified in 14 (6.0%) patients.In this study, we propose a novel use of NLP software to identify potentially malignant pancreatic lesions annotated in CT imaging performed for other purposes. This methodology can significantly increase the screening and automated referral for the management of precancerous lesions.

Published
2022

6. Freshly Thawed Cryobanked Human Neural Stem Cells Engraft within Endogenous Neurogenic Niches and Restore Cognitive Function after Chronic Traumatic Brain Injury

Author

Emily K. Reinhardt, Theodore V. Nguyen, Andrew T Marshall, Vincent Torrecampo, Javier Lepe, Karla Echeverria, Nicole Midani, Sara H. Bertan, Serinee H. Tran, Cherie A Lepe, Brian J. Cummings, Anna Badner, and Aileen J. Anderson

Subjects
Male, 030506 rehabilitation, Traumatic brain injury, Neurogenesis, Endogeny, Proteomics, Cell therapy, 03 medical and health sciences, Rats, Nude, 0302 clinical medicine, Cerebrospinal fluid, Cognition, Neural Stem Cells, Brain Injuries, Traumatic, Brain Injury, Chronic, Medicine, Animals, Humans, Stem Cell Niche, Biological Specimen Banks, Cryopreservation, business.industry, medicine.disease, Neural stem cell, nervous system diseases, Rats, Disease Models, Animal, nervous system, Neurology (clinical), 0305 other medical science, business, Neuroscience, 030217 neurology & neurosurgery, Stem Cell Transplantation
Abstract

Human neural stem cells (hNSCs) have potential as a cell therapy after traumatic brain injury (TBI). While various studies have demonstrated the efficacy of NSCs from ongoing culture, there is a significant gap in our understanding of freshly thawed cells from cryobanked stocks-a more clinically relevant source. To address these shortfalls, the therapeutic potential of our previously validated Shef-6.0 human embryonic stem cell (hESC)-derived hNSC line was tested after long-term cryostorage and thawing before transplant. Immunodeficient athymic nude rats received a moderate unilateral controlled cortical impact (CCI) injury. At four weeks post-injury, 6

Published
2021

8. Freshly Thawed Cryobanked Human Neural Stem Cells Engraft within Endogenous Neurogenic Niches and Restore Cognitive Function Following Chronic Traumatic Brain Injury

Author

Serinee H. Tran, Vincent Torrecampo, Andrew T Marshall, Emily K. Reinhardt, Javier Lepe, Theodore V. Nguyen, Anna Badner, Nicole Midani, Karla Echeverria, Brian J. Cummings, Aileen J. Anderson, Sara H. Bertan, and Cherie A Lepe

Subjects
Transplantation, Cell therapy, business.industry, Dentate gyrus, Neurogenesis, Medicine, Morris water navigation task, Progenitor cell, business, Neuroscience, Neuroinflammation, Neural stem cell
Abstract

Human neural stem cells (hNSCs) have potential as a cell therapy following traumatic brain injury (TBI). While various studies have demonstrated the efficacy of NSCs from on-going culture, there is a significant gap in our understanding of freshly thawed cells from cryobanked stocks – a more clinically-relevant source. To address these shortfalls, the therapeutic potential of our previously validated Shef-6.0 human embryonic stem cell (hESC)-derived hNSC line was tested following long-term cryostorage and thawing prior to transplant. Immunodeficient athymic nude rats received a moderate unilateral controlled cortical impact (CCI) injury. At 4-weeks post-injury, 6×105 freshly thawed hNSCs were transplanted into six injection sites (2 ipsi- and 4 contra-lateral) with 53.4% of cells surviving three months post-transplant. Interestingly, most hNSCs were engrafted in the meninges and the lining of lateral ventricles, associated with high CXCR4 expression and a chemotactic response to SDF1alpha (CXCL12). While some expressed markers of neuron, astrocyte, and oligodendrocyte lineages, the majority remained progenitors, identified through doublecortin expression (78.1%). Importantly, transplantation resulted in improved spatial learning and memory in Morris water maze navigation and reduced risk-taking behavior in an elevated plus maze. Investigating potential mechanisms of action, we identified an increase in ipsilateral host hippocampus cornu ammonis (CA) neuron survival, contralateral dentate gyrus (DG) volume and DG neural progenitor morphology as well as a reduction in neuroinflammation. Together, these findings validate the potential of hNSCs to restore function after TBI and demonstrate that long-term bio-banking of cells and thawing aliquots prior to use may be suitable for clinical deployment.Significance StatementThere is no cure for chronic traumatic brain injury (TBI). While human neural stem cells (hNSCs) offer a potential treatment, no one has demonstrated efficacy of thawed hNSCs from long-term cryobanked stocks. Frozen aliquots are critical for multisite clinical trials, as this omission impacted the use of MSCs for graft versus host disease. This is the first study to demonstrate the efficacy of thawed hNSCs, while also providing support for novel mechanisms of action – linking meningeal and ventricular engraftment to reduced neuroinflammation and improved hippocampal neurogenesis. Importantly, these changes also led to clinically relevant effects on spatial learning/memory and risk-taking behavior. Together, this new understanding of hNSCs lays a foundation for future work and improved opportunities for patient care.

Published
2020
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9. Raman spectra and elastic light scattering dynamics of V3O5 across insulator–metal transition

Author

Gabriel A. Goenaga, Jia-An Yan, Karla Echeverria, Armando Rúa, Nardeep Kumar, Félix E. Fernández, Jun-Qiang Lu, Sergiy Lysenko, Larry Theran, Samuel P. Hernández-Rivera, and Leonardo Ramos

Subjects
010302 applied physics, Phase transition, Materials science, Condensed matter physics, Phonon, Scattering, General Physics and Astronomy, 02 engineering and technology, 021001 nanoscience & nanotechnology, 01 natural sciences, symbols.namesake, Picosecond, 0103 physical sciences, Thermal, Homogeneity (physics), symbols, 0210 nano-technology, Raman spectroscopy, Ultrashort pulse
Abstract

The observation of Raman-active mode softening is a powerful tool to understand phase transition mechanisms in solids. The evolution of the phonon spectrum of technologically important correlated oxide V 3O 5 attracts much attention for the steady-state regime and for ultrashort temporal scales since thermal contribution to the insulator-to-metal (IMT) transition is excluded during the first few picoseconds. Here, we show theoretical modeling of V 3O 5 phonon spectrum and experiment. It is shown that the IMT is a first-order phase transition. Photoinduced transition was observed by a elastic light scattering technique, showing the principal difference in V 3O 5 surface dynamics across IMT for thermally and ultrafast light-induced phase transitions. The ultrafast IMT is accompanied primarily by short-range optical phonon interactions with a negligible contribution by acoustic phonons, while the acoustic phonons provide a key contribution to the transformation of surface geometry upon thermally induced IMT. Scattering imaging of surface autocorrelation function upon IMT shows the rise of optical homogeneity in the lateral direction of the surface in the steady-state regime and on a subpicosecond time scale.

Published
2021
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10. Development of a Chimeric Model to Study and Manipulate Human Microglia In Vivo

Author

Karla Echeverria, Mahshad Kolahdouzan, Christel Claes, Amanda McQuade, Robert C. Spitale, Taylor Nakayama, Hayk Davtyan, Jonathan Hasselmann, Morgan A. Coburn, Brian J. Cummings, Luke M. Healy, Ricardo Azevedo, Mathew Blurton-Jones, Sepideh Kiani Shabestari, Dario X. Figueroa Velez, Whitney England, Nicole G. Coufal, Claudia Z. Han, Christina H. Tu, Christopher K. Glass, and Sunil P. Gandhi

Subjects
0301 basic medicine, Induced Pluripotent Stem Cells, Gene Expression, Mice, Transgenic, Plaque, Amyloid, Biology, Transcriptome, 03 medical and health sciences, Chimera (genetics), Mice, 0302 clinical medicine, Alzheimer Disease, medicine, Animals, Humans, Transplantation Chimera, Amyloid beta-Peptides, Microglia, General Neuroscience, Macrophage Colony-Stimulating Factor, Neurodegeneration, Hematopoietic Stem Cell Transplantation, Brain, Granulocyte-Macrophage Colony-Stimulating Factor, Cell Differentiation, Gene signature, medicine.disease, Transplantation, Haematopoiesis, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, nervous system, Thrombopoietin, Stem cell, Neuroscience, 030217 neurology & neurosurgery
Abstract

iPSC-derived microglia offer a powerful tool to study microglial homeostasis and disease-associated inflammatory responses. Yet, microglia are highly sensitive to their environment, exhibiting transcriptomic deficiencies when kept in isolation from the brain. Furthermore, species-specific genetic variations demonstrate that rodent microglia fail to fully recapitulate the human condition. To address this, we developed an approach to study human microglia within a surrogate brain environment. Transplantation of iPSC-derived hematopoietic-progenitors into the postnatal brain of humanized, immune-deficient mice results in context-dependent differentiation into microglia and other CNS macrophages, acquisition of an ex vivo human microglial gene signature, and responsiveness to both acute and chronic insults. Most notably, transplanted microglia exhibit robust transcriptional responses to Aβ-plaques that only partially overlap with that of murine microglia, revealing new, human-specific Aβ-responsive genes. We therefore have demonstrated that this chimeric model provides a powerful new system to examine the in vivo function of patient-derived and genetically modified microglia.

Published
2019

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