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Articles 1201 - 1230 of 6644
Full-Text Articles in Entire DC Network
Community Firearm Violence And Dental Care Use In Middle Adulthood, Alexander Testa, Luis Mijares, Daniel Semenza, Richard Stansfield, Ian Silver, Dylan B Jackson, Ana Neumann, Jeff R Temple, Rahma Mungia
Community Firearm Violence And Dental Care Use In Middle Adulthood, Alexander Testa, Luis Mijares, Daniel Semenza, Richard Stansfield, Ian Silver, Dylan B Jackson, Ana Neumann, Jeff R Temple, Rahma Mungia
Faculty, Staff and Student Publications
Prior research links violence inside the home to reduced dental care utilization, yet little is known about how community firearm violence affects dental care behaviors. The current study used data from wave V (2016-2018) of the National Longitudinal Study of Adolescent to Adult Health (Add Health), linked to census tract-level fatal and nonfatal shooting data from the American Violence Project for the 100 largest cities in the United States. The analytic sample included 1925 respondents aged 33-42. The primary outcome was self-reported dental care use in the past year. Firearm violence exposure was categorized as 0, 1, or 2 + …
Treatment-Related Adverse Events And Associated Outcomes In Patients With Advanced Urothelial Carcinoma Treated With Enfortumab Vedotin: Analysis Of The Unite Study, Amanda Nizam, Charles B Nguyen, Jinju Li, Emily C Zabor, Pavlos Msaouel, Cindy Y Jiang, Omar Alhalabi, Eugene Oh, Matthew P Davidsohn, Ilana B Epstein, Dimitra Rafailia Bakaloudi, Rafee Talukder, Tanya Jindal, Amy K Taylor, Michael J Glover, Ali Raza Khaki, Emily Lemke, Hannah Mabey, Bashar Abuqayas, Albert Jang, Jason R Brown, Sean T Evans, Cameron Pywell, Arnab Basu, Mehmet A Bilen, Pedro C Barata, Yousef Zakharia, Matthew I Milowsky, Deepak Kilari, Christopher J Hoimes, Sumit A Shah, Hamid Emamekhoo, Nancy B Davis, Shilpa Gupta, Petros Grivas, Joaquim Bellmunt, Matthew T Campbell, Ajjai S Alva, Vadim S Koshkin
Treatment-Related Adverse Events And Associated Outcomes In Patients With Advanced Urothelial Carcinoma Treated With Enfortumab Vedotin: Analysis Of The Unite Study, Amanda Nizam, Charles B Nguyen, Jinju Li, Emily C Zabor, Pavlos Msaouel, Cindy Y Jiang, Omar Alhalabi, Eugene Oh, Matthew P Davidsohn, Ilana B Epstein, Dimitra Rafailia Bakaloudi, Rafee Talukder, Tanya Jindal, Amy K Taylor, Michael J Glover, Ali Raza Khaki, Emily Lemke, Hannah Mabey, Bashar Abuqayas, Albert Jang, Jason R Brown, Sean T Evans, Cameron Pywell, Arnab Basu, Mehmet A Bilen, Pedro C Barata, Yousef Zakharia, Matthew I Milowsky, Deepak Kilari, Christopher J Hoimes, Sumit A Shah, Hamid Emamekhoo, Nancy B Davis, Shilpa Gupta, Petros Grivas, Joaquim Bellmunt, Matthew T Campbell, Ajjai S Alva, Vadim S Koshkin
Faculty, Staff and Students Publications
Introduction: Enfortumab vedotin-ejfv (EV), an antibody-drug conjugate approved for advanced urothelial carcinoma (aUC), has limited real-world safety data and no validated predictive biomarkers. Retrospective studies suggest higher objective response rates (ORR) among patients developing EV-related dermatologic toxicities, but survival implications remain unclear. This analysis assessed the safety of EV monotherapy and the impact of dermatologic and neurologic toxicities on efficacy outcomes in a multi-institutional cohort.
Materials and methods: UNITE is a multicenter, retrospective study across 16 US sites of patients with aUC treated with targeted agents, including EV. Primary endpoints were the incidence of EV treatment-related adverse events (TRAEs, any …
High Prevalence Of Abnormal Baseline Lung Function In Pediatric And Young Adult Hematopoietic Stem Cell Transplant Recipients: A Report From The Transpire Study, Jane Koo, Richard Cooper, Stephanie L Edwards, Adam Lane, Sara Katherine Loveless, Lauren Strecker, Kelly E Lake, Kasiani C Myers, Christopher Towe, Jessica Patti, Laura L Walkup, Kathryn A Wikenheiser-Brokamp, Margaret L Macmillan, Philip Lacher, Tamara Griffin, Merve Tekman, Gabriel Salinas Cisneros, Kevin Wu, Matthew S Zinter, Fernando A Urrego, K Scott Baker, Matthew F Abts, Sheri Ballard, Jason L Freedman, Alexander Caraballo, Lisa R Young, Maureen B Josephson, Julian L Allen, Devaney M Camburn, Erin E Doherty, Mashid Sababi Azamian, Martha Arredondo, Manuel Silva-Carmona, Leslie E Lehmann, Wai Wong, Jonathan M Gaffin, William Mcalpine, Mona Li, Samuel B Goldfarb, Jason C Woods, Stella M Davies
High Prevalence Of Abnormal Baseline Lung Function In Pediatric And Young Adult Hematopoietic Stem Cell Transplant Recipients: A Report From The Transpire Study, Jane Koo, Richard Cooper, Stephanie L Edwards, Adam Lane, Sara Katherine Loveless, Lauren Strecker, Kelly E Lake, Kasiani C Myers, Christopher Towe, Jessica Patti, Laura L Walkup, Kathryn A Wikenheiser-Brokamp, Margaret L Macmillan, Philip Lacher, Tamara Griffin, Merve Tekman, Gabriel Salinas Cisneros, Kevin Wu, Matthew S Zinter, Fernando A Urrego, K Scott Baker, Matthew F Abts, Sheri Ballard, Jason L Freedman, Alexander Caraballo, Lisa R Young, Maureen B Josephson, Julian L Allen, Devaney M Camburn, Erin E Doherty, Mashid Sababi Azamian, Martha Arredondo, Manuel Silva-Carmona, Leslie E Lehmann, Wai Wong, Jonathan M Gaffin, William Mcalpine, Mona Li, Samuel B Goldfarb, Jason C Woods, Stella M Davies
Faculty, Staff and Students Publications
Background: Pulmonary complications are a major cause of morbidity and mortality in pediatric and young adult hematopoietic stem cell transplant (HSCT) recipients. The impact of preexisting lung dysfunction on posttransplant outcomes remains understudied.
Methods: In a multi-institutional prospective cohort of 444 patients (≤24 years) undergoing allogeneic HSCT at eight centers, baseline lung function was categorized as normal or abnormal using clinical history, imaging, pulmonary function tests (PFTs), and pulmonologist review. Spirometry and diffusion capacity were assessed at baseline, Day 100, 1 year, and 2 years post-HSCT.
Results: Baseline pulmonary dysfunction was present in 224 patients (50.4%), including impaired spirometry (46.4%), …
Transdiagnostic Correlates Of Family Accommodation In Anxious Youth, Whitney S Shepherd, Erika S Trent, Orri Smarason, Hannah N Sansone, Daphne M Ayton, Amanda Palo, Abigail E Candelari, Wayne K Goodman, Andrew G Guzick, Eric A Storch
Transdiagnostic Correlates Of Family Accommodation In Anxious Youth, Whitney S Shepherd, Erika S Trent, Orri Smarason, Hannah N Sansone, Daphne M Ayton, Amanda Palo, Abigail E Candelari, Wayne K Goodman, Andrew G Guzick, Eric A Storch
Faculty, Staff and Students Publications
Anxiety disorders are common in children and cause significant impairment. Family accommodation, which refers to behavioral changes that family members make to temporarily alleviate a child’s anxiety, has been linked to child anxiety symptom severity. Although emotional vulnerabilities for anxiety such as emotion dysregulation, anxiety sensitivity, and distress intolerance have been associated with family accommodation, research concerning the relationship between these constructs among anxious youth is limited. We hypothesized that these variables would be uniquely and positively associated with family accommodation and would moderate the relationship between anxiety symptom severity and family accommodation. Treatment-seeking child–parent dyads (N = 90; …
Effects Of The Kcnq (Kv7) Channel Opener Ezogabine On Resting-State Functional Connectivity Of Striatal Brain Reward Regions, Depression, And Anhedonia In Major Depressive Disorder: Results From A Randomized Controlled Trial, Avijit Chowdhury, Sarah Boukezzi, Sara Costi, Sara Hameed, Yael Jacob, Ramiro Salas, Dan V Iosifescu, Ming-Hu Han, Alan Swann, Sanjay J Mathew, Laurel Morris, James W Murrough
Effects Of The Kcnq (Kv7) Channel Opener Ezogabine On Resting-State Functional Connectivity Of Striatal Brain Reward Regions, Depression, And Anhedonia In Major Depressive Disorder: Results From A Randomized Controlled Trial, Avijit Chowdhury, Sarah Boukezzi, Sara Costi, Sara Hameed, Yael Jacob, Ramiro Salas, Dan V Iosifescu, Ming-Hu Han, Alan Swann, Sanjay J Mathew, Laurel Morris, James W Murrough
Faculty, Staff and Students Publications
Background: Major depressive disorder (MDD) is a leading cause of disability worldwide, with available treatments often showing limited efficacy. Recent research suggests that targeting specific subtypes of depression and understanding the underlying brain mechanisms can improve treatment outcomes. This study investigates the potential of the potassium KCNQ (Kv7) channel opener ezogabine to modulate the resting-state functional connectivity (RSFC) of the brain's reward circuitry and alleviate depressive symptoms, including anhedonia, a core feature of MDD.
Methods: A double-blind, randomized, placebo-controlled clinical trial in individuals with MDD ages 18 to 65 years compared daily dosing with ezogabine (n= 19) with placebo (n …
Natriuretic Peptide Cut Points For Heart Failure Classification In Individuals With And Without Obesity, Mandana Chitsazan, Juhi K Parekh, Leah B Kosyakovsky, Sophie M Nemeth, Emily S Lau, James L Januzzi, Thomas J Wang, Daniel Levy, Chiadi E Ndumele, Elizabeth Selvin, Christie M Ballantyne, Bruce M Psaty, John S Gottdiener, Jorge R Kizer, Christopher R Defilippi, Norrina B Allen, Rudolf A De Boer, Sanjiv J Shah, Jennifer E Ho
Natriuretic Peptide Cut Points For Heart Failure Classification In Individuals With And Without Obesity, Mandana Chitsazan, Juhi K Parekh, Leah B Kosyakovsky, Sophie M Nemeth, Emily S Lau, James L Januzzi, Thomas J Wang, Daniel Levy, Chiadi E Ndumele, Elizabeth Selvin, Christie M Ballantyne, Bruce M Psaty, John S Gottdiener, Jorge R Kizer, Christopher R Defilippi, Norrina B Allen, Rudolf A De Boer, Sanjiv J Shah, Jennifer E Ho
Faculty, Staff and Students Publications
Background: The 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America guidelines introduced elevated natriuretic peptide (NP) levels as a criterion for defining stage B heart failure (HF), or pre-HF, to identify individuals at greatest risk for future HF. Given the known NP deficiency in obesity, we aimed to assess whether a single NP cut point would disproportionately up-classify individuals with versus without obesity to stage B HF.
Methods: Participants free of HF from 5 community-based cohorts were included. We examined the reclassification of individuals to stage B HF using the 2022 versus 2013 guidelines, stratified by obesity …
Lp(A) Testing For The Primary Prevention Of Cardiovascular Disease In High-Income Countries: A Cost-Effectiveness Analysis, Jedidiah I Morton, Florian Kronenberg, Magdalena Daccord, Nicola Bedlington, Marius Geanta, Tobias Silberzahn, Zhenyue Chen, Jean-Luc Eisele, Bogi Eliasen, Mariko Harada-Shiba, Marc Rijken, Albert Wiegman, George Thanassoulis, Pia R Kamstrup, Iñaki Gutierrez-Ibarluzea, Pablo Coral, Raul D Santos, Erik Stroes, Michal Vrablik, Gerald F Watts, Christie M Ballantyne, Samia Mora, Børge G Nordestgaard, Kausik K Ray, Stephen J Nicholls, Zanfina Ademi, Lp(A) International Taskforce (Itf) Initiative
Lp(A) Testing For The Primary Prevention Of Cardiovascular Disease In High-Income Countries: A Cost-Effectiveness Analysis, Jedidiah I Morton, Florian Kronenberg, Magdalena Daccord, Nicola Bedlington, Marius Geanta, Tobias Silberzahn, Zhenyue Chen, Jean-Luc Eisele, Bogi Eliasen, Mariko Harada-Shiba, Marc Rijken, Albert Wiegman, George Thanassoulis, Pia R Kamstrup, Iñaki Gutierrez-Ibarluzea, Pablo Coral, Raul D Santos, Erik Stroes, Michal Vrablik, Gerald F Watts, Christie M Ballantyne, Samia Mora, Børge G Nordestgaard, Kausik K Ray, Stephen J Nicholls, Zanfina Ademi, Lp(A) International Taskforce (Itf) Initiative
Faculty, Staff and Students Publications
Background and aims: Cost-effectiveness of Lipoprotein(a) [Lp(a)] testing is not established. We aimed to evaluate the cost-effectiveness of Lp(a) testing in the cardiovascular disease (CVD) primary prevention population from healthcare and societal perspectives.
Methods: We constructed and validated a multi-state microsimulation Markov model for a population of 10,000 individuals aged between 40 and 69 years without CVD, selected randomly from the UK Biobank. The model evaluated Lp(a) testing in individuals not initially classified as high-risk based on age, diabetes status, or the SCORE-2 algorithm. Those with an Lp(a) level ≥105 nmol/L (50 mg/dL) were treated as high risk (initiation of …
Pfas Exposure And Postoperative Weight Regain In Adolescents After Bariatric Surgery: Findings From The Teen-Labs Study, Brittney O Baumert, Elizabeth Costello, Zhenjiang Li, Justin R Ryder, Thomas Inge, Todd Jenkins, Stephanie Sisley, Stavra A Xanthakos, Douglas I Walker, Nikos Stratakis, Damaskini Valvi, Scott M Bartell, Angela L Slitt, Rohit Kohli, Sarah Rock, Michele A La Merrill, Sandrah P Eckel, Max T Aung, Rob Mcconnell, David V Conti, Lida Chatzi
Pfas Exposure And Postoperative Weight Regain In Adolescents After Bariatric Surgery: Findings From The Teen-Labs Study, Brittney O Baumert, Elizabeth Costello, Zhenjiang Li, Justin R Ryder, Thomas Inge, Todd Jenkins, Stephanie Sisley, Stavra A Xanthakos, Douglas I Walker, Nikos Stratakis, Damaskini Valvi, Scott M Bartell, Angela L Slitt, Rohit Kohli, Sarah Rock, Michele A La Merrill, Sandrah P Eckel, Max T Aung, Rob Mcconnell, David V Conti, Lida Chatzi
Faculty, Staff and Students Publications
Objective: Weight regain following bariatric surgery remains a clinical challenge, with limited understanding of contributing environmental factors. Per- and polyfluoroalkyl substances (PFAS), persistent chemicals linked to metabolic dysfunction, may influence long-term weight trajectories. This study aimed to evaluate associations between PFAS exposure and changes in BMI, percent weight loss, and waist circumference among adolescents after bariatric surgery.
Methods: We included 186 adolescents (mean age: 17.1 years; 76.3% female; 72.0% White) from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort who underwent surgery between 2007 and 2012. Anthropometric measurements were collected at baseline and 6, 12, 36, and 60 months post …
Examining The Relationship Between Dysphagia, Eating-Related Symptoms, And Diet Quality Among Oropharyngeal Cancer Patients During Critical Stages Of Cancer Survivorship: The U-Dine Study, Beatrice Manduchi, Vlad C Sandulache, Ji Yun Tark, Shreela Sharma, Ruosha Li, Emily Roller, Andrew Bevelhimer, Katherine A Hutcheson, Marcia C De Oliveira Otto
Examining The Relationship Between Dysphagia, Eating-Related Symptoms, And Diet Quality Among Oropharyngeal Cancer Patients During Critical Stages Of Cancer Survivorship: The U-Dine Study, Beatrice Manduchi, Vlad C Sandulache, Ji Yun Tark, Shreela Sharma, Ruosha Li, Emily Roller, Andrew Bevelhimer, Katherine A Hutcheson, Marcia C De Oliveira Otto
Faculty, Staff and Students Publications
Background: Diet quality is a modifiable factor impacting treatment outcomes in oropharyngeal cancer (OPC), yet the effect of dysphagia and self-reported eating-related symptoms remains unclear. This study examined their associations with diet quality in OPC patients.
Methods: A cross-sectional analysis was conducted with two parallel cohorts from MD Anderson Cancer Center and Michael E. DeBakey Veterans Affairs Medical Center as part of the Uncovering the Long-Term Impact of OPC and Dysphagia on Dietary Quality and Nutrition Among Cancer Survivors (U-DINE) Study. Participants at varying survivorship stages (prediagnosis, 3-6 and 18+ months posttreatment) were assessed for dysphagia (DIGEST scale) and six …
Bi-Allelic Loss-Of-Function Variants In Poc5 Cause A Syndromic Retinal, Endocrine, And Neuromuscular Ciliopathy, Anneke T Vulto-Van Silfhout, Ingrid M Jazet, Suzanne Yzer, Jeroen Pas, Serwet Demirdas, Elisabeth F C Van Rossum, Alberta A H J Thiadens, Ronald Van Beek, Lonneke Haer-Wigman, Daniela Q C M Barge-Schaapveld, Charlotte Brasch-Andersen, Simon Frost, Miriam Bauwens, Elfride De Baere, Irina Balikova, Filip Van Den Broeck, Monika Weisz-Hubshman, Pascal Joset, Peter Miny, Isabel Filges, Susanne Kohl, Pietro De Angeli, Laura Kühlewein, Jan-Philipp Bodenbender, Tobias Haack, Karin Poths, Lidia Fernandez-Caballero, Marta Corton, Fiona Blanco Kelly, Carmen Ayuso, Peggy Martínez-Esteban, John Vissing, Jordi Díaz-Manera, Volker Straub, Ana Töpf, Siying Lin, Gavin Arno, William L Macken, Jennifer Spillane, Radha Ramachandran, Erik De Vrieze, Tjakko Van Ham, Susanne Roosing, Machteld M Oud
Bi-Allelic Loss-Of-Function Variants In Poc5 Cause A Syndromic Retinal, Endocrine, And Neuromuscular Ciliopathy, Anneke T Vulto-Van Silfhout, Ingrid M Jazet, Suzanne Yzer, Jeroen Pas, Serwet Demirdas, Elisabeth F C Van Rossum, Alberta A H J Thiadens, Ronald Van Beek, Lonneke Haer-Wigman, Daniela Q C M Barge-Schaapveld, Charlotte Brasch-Andersen, Simon Frost, Miriam Bauwens, Elfride De Baere, Irina Balikova, Filip Van Den Broeck, Monika Weisz-Hubshman, Pascal Joset, Peter Miny, Isabel Filges, Susanne Kohl, Pietro De Angeli, Laura Kühlewein, Jan-Philipp Bodenbender, Tobias Haack, Karin Poths, Lidia Fernandez-Caballero, Marta Corton, Fiona Blanco Kelly, Carmen Ayuso, Peggy Martínez-Esteban, John Vissing, Jordi Díaz-Manera, Volker Straub, Ana Töpf, Siying Lin, Gavin Arno, William L Macken, Jennifer Spillane, Radha Ramachandran, Erik De Vrieze, Tjakko Van Ham, Susanne Roosing, Machteld M Oud
Faculty, Staff and Students Publications
Purpose: A homozygous loss-of-function (LoF) variant in POC5 was previously described in an individual with retinitis pigmentosa. We identified POC5 variants in 12 probands with a syndromic phenotype. We aim to define the phenotype spectrum and molecular mechanism associated with biallelic POC5 LoF variants.
Methods: We studied a cohort of 12 families with bi-allelic LoF POC5 variants and performed detailed phenotype analysis. POC5 localization studies were performed in 3 proband-derived fibroblast cell lines.
Results: Detailed phenotyping of probands with POC5 variants expands the phenotype spectrum beyond ocular manifestations. This syndrome causes not only rod-cone dystrophy but also diabetes mellitus with …
Is Bedtime Use Of Kratom (Mitragyna Speciosa) A Sleep Aid Or Disruptor? Examining Its Daily Effects And Individual Differences, Chung Jung Mun, Patricia Timmons, Leigh V Panlilio, Christopher D Verrico, Ynhi T Thomas, C Austin Zamarripa, David H Epstein, Kirsten E Smith
Is Bedtime Use Of Kratom (Mitragyna Speciosa) A Sleep Aid Or Disruptor? Examining Its Daily Effects And Individual Differences, Chung Jung Mun, Patricia Timmons, Leigh V Panlilio, Christopher D Verrico, Ynhi T Thomas, C Austin Zamarripa, David H Epstein, Kirsten E Smith
Faculty, Staff and Students Publications
Kratom (Mitragyna speciosa) is a psychoactive botanical native to Southeast Asia increasingly used in the U.S. for various self-reported benefits, including sleep improvement. However, empirical evidence concerning kratom’s effects on sleep is limited. Here, we examined the association between bedtime kratom use and self-reported sleep outcomes in naturalistic settings across consecutive days, while also exploring sex and chronic pain status as potential moderators. A secondary analysis was conducted using the data from a 15-day ecological momentary assessment (EMA) study of 357 U.S. adults who reported regularly using kratom. Participants made daily reports of their bedtime kratom use and …
Post-Deployment Monitoring Of Ai Performance In Intracranial Hemorrhage Detection By Chatgpt, Eric Rohren, Mohadese Ahmadzade, Sofia Colella, Nina Kottler, Sriyesh Krishnan, Jason Poff, Neelesh Rastogi, Walter Wiggins, Joyce Yee, Carlos Zuluaga, Phil Ramis, Mohammad Ghasemi-Rad
Post-Deployment Monitoring Of Ai Performance In Intracranial Hemorrhage Detection By Chatgpt, Eric Rohren, Mohadese Ahmadzade, Sofia Colella, Nina Kottler, Sriyesh Krishnan, Jason Poff, Neelesh Rastogi, Walter Wiggins, Joyce Yee, Carlos Zuluaga, Phil Ramis, Mohammad Ghasemi-Rad
Faculty, Staff and Students Publications
Rationale and objectives: To evaluate the post-deployment performance of an artificial intelligence (AI) system (Aidoc) for intracranial hemorrhage (ICH) detection and assess the utility of ChatGPT-4 Turbo for automated AI monitoring.
Materials and methods: This retrospective study evaluated 332,809 head CT examinations from 37 radiology practices across the United States (December 2023-May 2024). Of these, 13,569 cases were flagged as positive for ICH by the Aidoc AI system. A HIPAA (Health Insurance Portability and Accountability Act) -compliant version of ChatGPT-4 Turbo was used to extract data from radiology reports. Ground truth was established through radiologists' review of 200 randomly selected …
Prostaglandin E2 As A Mechanistic Biomarker Of Chronic Pancreatitis, Jami L Saloman, Bahiyyah Jefferson, Samuel Han, William E Fisher, Evan L Fogel, Phil A Hart, Liang Li, Walter G Park, Santhi Swaroop Vege, Dhiraj Yadav, Mark D Topazian, Darwin L Conwell
Prostaglandin E2 As A Mechanistic Biomarker Of Chronic Pancreatitis, Jami L Saloman, Bahiyyah Jefferson, Samuel Han, William E Fisher, Evan L Fogel, Phil A Hart, Liang Li, Walter G Park, Santhi Swaroop Vege, Dhiraj Yadav, Mark D Topazian, Darwin L Conwell
Faculty, Staff and Students Publications
Introduction: Chronic pancreatitis (CP) is a disease associated with chronic inflammation, fibrosis, and pain. There is a lack of tools available that facilitate early diagnosis, when intervention could prevent irreversible damage. Pilot data suggested prostaglandin E2 (PGE2) as a candidate biomarker for early CP. PGE2 activates signaling pathways that promote inflammation, pain, and fibrosis.
Methods: We assessed PGE2, metabolites, and downstream targets in pancreatic fluid collected endoscopically 0-10 (n = 110) and 10-20 (n = 111) minutes after intravenous secretin administration. PGE2 and metabolites were measured in plasma (n = 75) and urine (n = 71) from the same subjects. …
Implementation Of A Package Of Emergency Care Interventions And Clinical Outcomes, Corey B Bills, Paul Wesseh, Catherine Cooper, Taylor W Burkholder, Lane Epps, Michael Jaung, Emilie J Calvello Hynes, Alex Mayah, John K Shakpeh, Kayla Enriquez
Implementation Of A Package Of Emergency Care Interventions And Clinical Outcomes, Corey B Bills, Paul Wesseh, Catherine Cooper, Taylor W Burkholder, Lane Epps, Michael Jaung, Emilie J Calvello Hynes, Alex Mayah, John K Shakpeh, Kayla Enriquez
Faculty, Staff and Students Publications
Importance: Investments in emergency care systems are vital to ensuring universal health coverage and improving health outcomes in low- and middle-income countries.
Objective: To assess whether a package of emergency care interventions is associated with improved patient mortality and clinical care quality.
Design, setting, and participants: This pre-post quality improvement study was conducted at a single urban referral hospital emergency unit (EU) in Monrovia, Liberia, to assess clinical and educational outcomes resulting from the implementation of a package of interventions from January 1, 2018, through June 30, 2019. Final analysis was performed in November 2023. Data from a random subset …
Exploring The Transformative Effects Of Calorie Restriction On The Lacrimal Gland In Adult Mice, Olivier Mauduit, Prashant Kumar, Kaitlin K Scholand, Emre Aksan, Laura Schaefer, Anmar Abu-Romman, Vanessa Delcroix, Zhiyuan Yu, Aude I Sindikubwabo, Ron Korstanje, Helen P Makarenkova, Cintia S De Paiva
Exploring The Transformative Effects Of Calorie Restriction On The Lacrimal Gland In Adult Mice, Olivier Mauduit, Prashant Kumar, Kaitlin K Scholand, Emre Aksan, Laura Schaefer, Anmar Abu-Romman, Vanessa Delcroix, Zhiyuan Yu, Aude I Sindikubwabo, Ron Korstanje, Helen P Makarenkova, Cintia S De Paiva
Faculty, Staff and Students Publications
Advanced age is one of the most recognizable risk factors for dry eye. Dry eye disease affects millions worldwide and can result from age-related lacrimal gland dysfunction, which correlates with a decline in lacrimal gland secretory cell function and chronic inflammation. This study investigated the potential of calorie restriction to maintain lacrimal gland and ocular surface health. Adult female C57BL/6 J mice were subjected to a 40% calorie restriction for 4 months, starting at 6-7 months and continuing until 10-11 months. These mice were compared to controls fed ad libitum. Bulk RNA sequencing of lacrimal glands, conjunctiva, and cornea subjected …
Plasma Proteome Correlations With Liver Stiffness In Pediatric Cholestasis Implicate Epithelial To Mesenchymal Transition, Benjamin L Shneider, Rupa S Kanchi, Sandra L Grimm, Sridevi Devaraj, Juliet Emamaullee, Jeremy Schraw, Philip J Lupo, Jorge A Bezerra, Kathleen M Loomes, John C Magee, Ronald J Sokol, Kasper S Wang, Alyssa Kriegmeier, Evelyn Hsu, Jean P Molleston, Philip Rosenthal, Rohit Kohli, Saul J Karpen, Simon P Horslen, M Kyle Jensen, Arianna Barbetta, Cristian Coarfa
Plasma Proteome Correlations With Liver Stiffness In Pediatric Cholestasis Implicate Epithelial To Mesenchymal Transition, Benjamin L Shneider, Rupa S Kanchi, Sandra L Grimm, Sridevi Devaraj, Juliet Emamaullee, Jeremy Schraw, Philip J Lupo, Jorge A Bezerra, Kathleen M Loomes, John C Magee, Ronald J Sokol, Kasper S Wang, Alyssa Kriegmeier, Evelyn Hsu, Jean P Molleston, Philip Rosenthal, Rohit Kohli, Saul J Karpen, Simon P Horslen, M Kyle Jensen, Arianna Barbetta, Cristian Coarfa
Faculty, Staff and Students Publications
Background: Pediatric cholestatic liver diseases can be characterized by rapidly progressive fibrosis. A multicenter cross-sectional analysis of vibration-controlled elastography in biliary atresia (BA), alpha-1 antitrypsin deficiency (A1AT), and Alagille syndrome (ALGS) was leveraged to interrogate the plasma proteome relative to liver stiffness measurements (LSM).
Methods: Slow off-rate modified aptamer scanning profiling of >7000 proteins in plasma from 187 children with BA (n=93), A1AT (n=31), ALGS (n=46), and healthy pediatric controls (n=17) was performed, and correlations with LSM were undertaken.
Results: There was an abundance of LSM correlated proteins (BA n=2720, A1AT n=694, ALGS n=5968). Interestingly, a distinct plasma proteome was …
Hydrogen Sulfide Inhibits Recruitment Of Monocyte-Derived Tumor Associated Macrophages In Glioblastoma By Downregulating Cxcl12, Joseph Camarano, Morgan Roque, Gabrielle Gahn, Stephen Garrett Whipple, Danielle Terrell, Charles Ronkon, Jamie Toms, Anthony Sin, Bharat Guthikonda, Khatri Latha, Yuhui Yang, Xinggui Shen, Christopher G Kevil, Ganesh Rao, Sungho Lee
Hydrogen Sulfide Inhibits Recruitment Of Monocyte-Derived Tumor Associated Macrophages In Glioblastoma By Downregulating Cxcl12, Joseph Camarano, Morgan Roque, Gabrielle Gahn, Stephen Garrett Whipple, Danielle Terrell, Charles Ronkon, Jamie Toms, Anthony Sin, Bharat Guthikonda, Khatri Latha, Yuhui Yang, Xinggui Shen, Christopher G Kevil, Ganesh Rao, Sungho Lee
Faculty, Staff and Students Publications
Tumor associated macrophages (TAMs) directly contribute to the dismal prognosis of glioblastoma by preventing anti-tumor immunity and promoting tumor invasion and angiogenesis. Inhibiting TAM infiltration is a potential therapeutic strategy in glioblastoma, with several chemokine antagonists in early clinical development. Hydrogen sulfide, a gasotransmitter that regulates microglial accumulation in a wide range of CNS diseases, may be a novel therapeutic target to prevent TAM recruitment in glioblastoma. In this study, hydrogen sulfide concentrations were directly measured from 14 isocitrate dehydrogenase (IDH)-wildtype glioblastoma surgical samples and compared against overall survival as well as expression of TAM markers and chemokines. Effects of …
What Community Members With Chronic Illness Teach Future Healthcare Professionals In A Longitudinal Interprofessional Education Program: A Focus Group Study, Rachel White, Maria Brucato, Amber King, Anne B. Mitchell, Nethra S. Ankam
What Community Members With Chronic Illness Teach Future Healthcare Professionals In A Longitudinal Interprofessional Education Program: A Focus Group Study, Rachel White, Maria Brucato, Amber King, Anne B. Mitchell, Nethra S. Ankam
Department of Medicine Faculty Papers
INTRODUCTION: Nearly 50% of Americans have at least one chronic illness. Preparing future healthcare providers for interprofessional collaborative practice (IPCP) and person-centred care through community-based interprofessional education (IPE) can improve outcomes for this growing population. Partial programme theories predict that patients' participation as teachers in health professions education contributes to students' development of patient-centredness. Role theory asserts that behaviours are shaped by assigned roles; therefore, community members with chronic illness who assume roles of health mentors in an IPE curriculum are predicted to teach students about their patient experiences. Yet, this teaching outcome and the lessons health mentors teach in …
Dynamic Rewiring Of Microrna Networks In The Brainstem Autonomic Control Circuits During Hypertension Development In The Female Spontaneously Hypertensive Rat, Alison Moss, Ankita Srivastava, Lakshmi Kuttippurathu, James S. Schwaber, Rajanikanth Vadigepalli
Dynamic Rewiring Of Microrna Networks In The Brainstem Autonomic Control Circuits During Hypertension Development In The Female Spontaneously Hypertensive Rat, Alison Moss, Ankita Srivastava, Lakshmi Kuttippurathu, James S. Schwaber, Rajanikanth Vadigepalli
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
We describe global microRNA (miRNA) changes in the central autonomic control circuits during the development of neurogenic hypertension. Using the female spontaneously hypertensive rat (SHR) and the normotensive Wistar Kyoto (WKY), we analyzed the dynamic miRNA expression changes in three brainstem regions-the nucleus of the solitary tract, caudal ventrolateral medulla, and rostral ventrolateral medulla-as a time series beginning at 8 wk of age before hypertension onset through to extended chronic hypertension. Our analysis yielded nine miRNAs that were significantly differentially regulated in all three regions between SHR and WKY over time. We collated computationally predicted gene targets of these nine …
Analyzing The Learning Curve Of Vnotes Sacrocolpopexy By The Cumulative Summation Test: A Cohort Study, Wenyu Liu, Nannan Sun, Yuejiao Zhang, Yuyan Li, Weihao Lai, Youjun Zhou, Xiaoming Guan, Juan Liu
Analyzing The Learning Curve Of Vnotes Sacrocolpopexy By The Cumulative Summation Test: A Cohort Study, Wenyu Liu, Nannan Sun, Yuejiao Zhang, Yuyan Li, Weihao Lai, Youjun Zhou, Xiaoming Guan, Juan Liu
Faculty, Staff and Students Publications
Background: The learning curve of transvaginal natural orifice transluminal endoscopic sacrocolpopexy (vNOTES-SC) in the treat of pelvic organ prolapse (POP) is critical yet underexplored. Our objective is to describe the learning curve and surgical complications of vNOTES-SC, taking into account the factors that affect operative time and evaluate the long-term follow-up outcomes of this surgery.
Methods: We conducted a hospital-based cohort study involving patients who underwent vNOTES-SC from June 2017 to May 2024. All surgeries were performed by a single surgeon with over 20 years of surgical experience. This study employed cumulative summation test (CUSUM) analysis to quantify the learning …
Using Latent Patient-Centered Fear Extinction Profiles To Guide Treatment In Pediatric Ocd, Katherine M Ingram, Eric A Storch, Daniel A Geller, Brent J Small, Sabine Wilhelm, Joseph F Mcguire
Using Latent Patient-Centered Fear Extinction Profiles To Guide Treatment In Pediatric Ocd, Katherine M Ingram, Eric A Storch, Daniel A Geller, Brent J Small, Sabine Wilhelm, Joseph F Mcguire
Faculty, Staff and Students Publications
Background: While exposure with response prevention (ERP) is the frontline treatment for pediatric obsessive-compulsive disorder (OCD), not all patients benefit. Impairments in extinction learning are implicated in pediatric OCD's etiology and treatment, with impaired pre-treatment extinction learning associated with worse ERP outcomes. However, available methods for assessing patients' difficulties with fear extinction are costly and underdeveloped. In response, we used person-centered profiles to characterize latent fear extinction patterns among youth with OCD, and investigated the degree to which scores on common rating scales correspond to profile membership.
Methods: Youth with OCD (n=98) completed a diagnostic clinical battery followed by a …
Characterizing Measurement-Based Care In The Texas Youth Depression And Suicide Research Network (Tx-Ydsrn), Holli Slater, Yasmin Alzubi, Afsaneh Rezaeizadeh, Jennifer L Hughes, April Gorman, Taryn L Mayes, Joshua S Elmore, Eric A Storch, Sarah M Wakefield, Madhukar H Trivedi
Characterizing Measurement-Based Care In The Texas Youth Depression And Suicide Research Network (Tx-Ydsrn), Holli Slater, Yasmin Alzubi, Afsaneh Rezaeizadeh, Jennifer L Hughes, April Gorman, Taryn L Mayes, Joshua S Elmore, Eric A Storch, Sarah M Wakefield, Madhukar H Trivedi
Faculty, Staff and Students Publications
Integration of measurement-based care (MBC) into clinical practice has shown promise in improving treatment outcomes for depression. Yet, without a gold standard measure of MBC, assessing fidelity to the MBC model across various clinical settings is difficult. A central goal of the Texas Youth Depression and Suicide Research Network (TX-YDSRN) was to characterize MBC across the state of Texas through the development of a standardized tool to assess the use of MBC strategies when assessing depression, anxiety, side effects, and treatment adherence. A chart review of clinical visits indicated standardized depression measures (71.2%) and anxiety measures (64%) were being utilized …
Motivations, Facilitators, And Barriers Of Donation-Based Interventions In Hiv And Sexually Transmitted Infection Research: A Systematic Review, Dorian Ho, Ye Liu, Jamie Conklin, Thomas Fitzpatrick, Jiayu Wang, Suzanne Day, Takhona G Hlatshwako, Rohit Ramaswamy, Ruby Congjiang Wang, Eneyi E Kpokiri, Weiming Tang, Elvin Geng, Joseph D Tucker
Motivations, Facilitators, And Barriers Of Donation-Based Interventions In Hiv And Sexually Transmitted Infection Research: A Systematic Review, Dorian Ho, Ye Liu, Jamie Conklin, Thomas Fitzpatrick, Jiayu Wang, Suzanne Day, Takhona G Hlatshwako, Rohit Ramaswamy, Ruby Congjiang Wang, Eneyi E Kpokiri, Weiming Tang, Elvin Geng, Joseph D Tucker
2020-Current year OA Pubs
IMPORTANCE: Donation-based prosocial interventions involve someone receiving a free health service and then distributing or donating to support health services for others; examples within the HIV and sexually transmitted infection (STI) literature include secondary distribution of HIV self-tests, secondary syringe exchange, and pay it forward for STI testing. These interventions answer research and policy recommendations to incorporate prosocial behaviors into HIV/STI services.
OBJECTIVE: To describe motivations, facilitators, and barriers of donation-based interventions in HIV and STI research using data from qualitative studies.
EVIDENCE REVIEW: In this systematic review, 5 databases (PubMed, CINAHL, Embase, PsycInfo, and Scopus) and references were searched …
Timing Of Cardiac Resynchronization Therapy Following Stable Medical Therapy In Patients With Heart Failure, Alessandro Villaschi, Christian Basile, Lina Benson, Paolo Gatti, William T Abraham, Michael Böhm, Biykem Bozkurt, Javed Butler, Gianluigi Condorelli, Cecilia Linde, Marco Metra, Wilfried Mullens, Peter Mol, Shelley Zieroth, Raffaele Scorza, Lars H Lund, Fredrik Gadler, Gianluigi Savarese
Timing Of Cardiac Resynchronization Therapy Following Stable Medical Therapy In Patients With Heart Failure, Alessandro Villaschi, Christian Basile, Lina Benson, Paolo Gatti, William T Abraham, Michael Böhm, Biykem Bozkurt, Javed Butler, Gianluigi Condorelli, Cecilia Linde, Marco Metra, Wilfried Mullens, Peter Mol, Shelley Zieroth, Raffaele Scorza, Lars H Lund, Fredrik Gadler, Gianluigi Savarese
Faculty, Staff and Students Publications
Background: Guidelines' recommendations for cardiac resynchronization therapy (CRT) implantation in selected patients with heart failure (HF) exist. However, data on the best timing for CRT implantation after the achievement of stable medical therapy (SMT) and its association with outcomes are currently lacking.
Objectives: The aim of this study was to investigate the timing of CRT implantation after the achievement of SMT, associated patient profiles, and clinical outcomes in a real-world HF population.
Methods: Patients with HF treated with SMT derived from the Swedish ICD and Pacemaker Registry who received CRT between 2007 and 2020 were included in the study. Patient …
Carbonic Anhydrase Inhibition Sensitizes Group 3 Medulloblastoma To Radiotherapy, Cory M Richman, Alexandra Rasnitsyn, Borja L Holgado, Maria Vladoiu, Namal Abeysundara, Sandra Majo, Sara Chabi, Lucie J Taunay, Hiromichi Suzuki, Ichiyo Shibahara, Joonas Haapasalo, Jonelle G Pallotta, Tajana Douglas, Kaitlin Kharas, Kyle Juraschka, Oliver Ocsenas, Sachin A Kumar, Kristiina Nordfors, Ana Guerreiro Stücklin, Raul A Suarez, Jiao Zhang, Xiaochong Wu, Craig Daniels, Livia Garzia, Jüri Reimand, Olivier Saulnier, Thomas E Merchant, Celio Pouponnot, David R Raleigh, Michael D Taylor, Pasqualino De Antonellis
Carbonic Anhydrase Inhibition Sensitizes Group 3 Medulloblastoma To Radiotherapy, Cory M Richman, Alexandra Rasnitsyn, Borja L Holgado, Maria Vladoiu, Namal Abeysundara, Sandra Majo, Sara Chabi, Lucie J Taunay, Hiromichi Suzuki, Ichiyo Shibahara, Joonas Haapasalo, Jonelle G Pallotta, Tajana Douglas, Kaitlin Kharas, Kyle Juraschka, Oliver Ocsenas, Sachin A Kumar, Kristiina Nordfors, Ana Guerreiro Stücklin, Raul A Suarez, Jiao Zhang, Xiaochong Wu, Craig Daniels, Livia Garzia, Jüri Reimand, Olivier Saulnier, Thomas E Merchant, Celio Pouponnot, David R Raleigh, Michael D Taylor, Pasqualino De Antonellis
Faculty, Staff and Students Publications
Group 3 (G3) medulloblastoma constitutes the most aggressive molecular subgroup, and nearly all patients present with metastases upon recurrence. Treatment for newly diagnosed medulloblastoma relies on a combination of maximal safe surgical resection, followed by chemotherapy and ionizing radiation, and no therapies have been shown to confer a survival benefit at the time of recurrence. Given the limited therapeutic options available for patients with medulloblastoma, especially at recurrence, and the incomplete understanding of the molecular mechanisms underlying resistance to treatment, we sought to uncover actionable targets and biomarkers that could help refine patient selection and treatment of newly diagnosed medulloblastoma …
Dysphoric Milk Ejection Reflex: Prevalence And Associations With Self-Reported Mental Health History, Megan Howard, Alison N Goulding, Anitha Muddana, Terri L Fletcher, Nicole Cirino, Alison M Stuebe
Dysphoric Milk Ejection Reflex: Prevalence And Associations With Self-Reported Mental Health History, Megan Howard, Alison N Goulding, Anitha Muddana, Terri L Fletcher, Nicole Cirino, Alison M Stuebe
Faculty, Staff and Students Publications
This study sought to determine prevalence of Dysphoric Milk Ejection Reflex (D-MER) and mental health correlates in a cohort of patients from a breastfeeding medicine clinic. We determined prevalence of D-MER symptoms and performed bivariate analyses to explore associations between D-MER symptoms, demographics, and self-reported mental health history. Among 271 patients, 42 (15.5%) reported D-MER. Women with D-MER symptoms were more likely to report a history of panic attacks (28.6 vs. 12.2%, OR 2.87, 95% CI 1.23-6.25).
Endoglin-Directed Car T Cells Comprehensively Target Tumors In Advanced Sarcomas, Harrison R Berger, Malina Maharana, Jeneffer Mirabal, Lyazat Kurenbekova, Alberto Delaidelli, Atreyi Dasgupta, Ahmed Z Gad, Mohamed F Sheha, Sybrina S Kerr, Ada I Ozcan, Jessica S Morris, Angela M Major, M John Hicks, Mary K Mckenna, Ben K Seon, Matthew L Baker, Poul H Sorensen, Meenakshi Hegde, Jason T Yustein, Nabil Ahmed, Sujith K Joseph
Endoglin-Directed Car T Cells Comprehensively Target Tumors In Advanced Sarcomas, Harrison R Berger, Malina Maharana, Jeneffer Mirabal, Lyazat Kurenbekova, Alberto Delaidelli, Atreyi Dasgupta, Ahmed Z Gad, Mohamed F Sheha, Sybrina S Kerr, Ada I Ozcan, Jessica S Morris, Angela M Major, M John Hicks, Mary K Mckenna, Ben K Seon, Matthew L Baker, Poul H Sorensen, Meenakshi Hegde, Jason T Yustein, Nabil Ahmed, Sujith K Joseph
Faculty, Staff and Students Publications
There are limited therapeutic options for patients with advanced sarcomas, which leads to dismal outcomes for children and adults. Although chimeric antigen receptor (CAR) T cells hold promise for treating advanced sarcomas, this approach is constrained by a paucity of effective targets. Our previous clinical study identified endoglin (ENG/CD105), a TGFβ coreceptor, as a target of the endogenous immune response in a patient with sarcoma who exhibited an exceptional response to HER2-targeted CAR T-cell therapy. ENG is expressed on various sarcomas, cancer-associated fibroblasts, and neoangiogenic vessels and therefore offers comprehensive tumor targeting. Furthermore, ENG knockout in sarcoma cells reduces their …
Exploring Patients' Perceptions Of An Advance Care Planning Intervention In The Emergency Department: A Qualitative Study, Youkie Shiozawa, Saaya Morton, Nanako Shirai, Hannah Oelschlager, Lucy Kiernat, Anita N Chary, Anna C Revette, Adrian Haimovich, Smit Desai, Kai-Wei Chang, Shan W Liu, Maura Kennedy, Mara A Schonberg, Kei Ouchi
Exploring Patients' Perceptions Of An Advance Care Planning Intervention In The Emergency Department: A Qualitative Study, Youkie Shiozawa, Saaya Morton, Nanako Shirai, Hannah Oelschlager, Lucy Kiernat, Anita N Chary, Anna C Revette, Adrian Haimovich, Smit Desai, Kai-Wei Chang, Shan W Liu, Maura Kennedy, Mara A Schonberg, Kei Ouchi
Faculty, Staff and Students Publications
Objectives: Emergency department (ED) visits offer opportunities for seriously ill patients to formulate future medical care goals, yet ED clinicians lack practical strategies for these conversations. ED GOAL, a behavioral intervention, engages seriously ill yet clinically stable older adults in the ED to address advance care planning (ACP) with their outpatient clinicians. In a randomized trial, goals-of-care documentation was significantly higher in the intervention group compared to controls after three (24.3% vs. 9.9%, p = 0.03) and 6 months (31.4% vs. 12.7%, p < 0.01). This study is a sub-analysis to learn about intervention arm participants' perceived benefits and obstacles of the intervention.
Methods: We conducted semi-structured interviews between October 2022 and August 2024 (N = 52) with intervention-arm patients …
Visual And Quantitative Interstitial Lung Abnormality Progression In Copdgene, Rachel K Putman, Jonathan A Rose, Ruben San José Estepar, Ann-Marcia C Tukpah, Claire C Cutting, Takuya Hino, Akinori Hata, Mizuki Nishino, Stephen M Humphries, David A Lynch, Edwin K Silverman, Michael H Cho, Ivan O Rosas, George R Washko, Hiroto Hatabu, Raúl San José Estepar, Gary M Hunninghake
Visual And Quantitative Interstitial Lung Abnormality Progression In Copdgene, Rachel K Putman, Jonathan A Rose, Ruben San José Estepar, Ann-Marcia C Tukpah, Claire C Cutting, Takuya Hino, Akinori Hata, Mizuki Nishino, Stephen M Humphries, David A Lynch, Edwin K Silverman, Michael H Cho, Ivan O Rosas, George R Washko, Hiroto Hatabu, Raúl San José Estepar, Gary M Hunninghake
Faculty, Staff and Students Publications
Rationale: Interstitial lung abnormalities (ILAs) are visually identified changes on chest computed tomography (CT) scans that may represent early or mild pulmonary fibrosis. Quantitative interstitial abnormalities (QIAs) measure potential parenchymal lung injury on chest CT scans using an automated algorithm. It is not known if combining these visual and quantitative assessments improves prediction of imaging progression.
Objectives: To assess the utility of quantitative imaging to predict imaging progression of ILAs and adverse clinical outcomes in a cohort of smokers.
Methods: ILA presence, subtypes, and progression, as well as QIAs, were assessed on chest CT scans from participants ∼5 years apart …
Engineered Exosomes With Krasg12d Specific Sirna In Pancreatic Cancer: A Phase I Study With Immunological Correlates, Valerie S Kalluri, Brandon G Smaglo, Krishnan K Mahadevan, Michelle L Kirtley, Kathleen M Mcandrews, Mayela Mendt, Sujuan Yang, Ana S Maldonado, Hikaru Sugimoto, Maria E Salvatierra, Luisa M Solis Soto, Cara Haymaker, Rick Finch, Mihai Gagea, Adam C Fluty, Steven J Ludtke, J Jack Lee, Abhinav K Jain, Gauri Varadhachary, Rachna T Shroff, Anirban Maitra, Elizabeth Shpall, Shubham Pant, Raghu Kalluri
Engineered Exosomes With Krasg12d Specific Sirna In Pancreatic Cancer: A Phase I Study With Immunological Correlates, Valerie S Kalluri, Brandon G Smaglo, Krishnan K Mahadevan, Michelle L Kirtley, Kathleen M Mcandrews, Mayela Mendt, Sujuan Yang, Ana S Maldonado, Hikaru Sugimoto, Maria E Salvatierra, Luisa M Solis Soto, Cara Haymaker, Rick Finch, Mihai Gagea, Adam C Fluty, Steven J Ludtke, J Jack Lee, Abhinav K Jain, Gauri Varadhachary, Rachna T Shroff, Anirban Maitra, Elizabeth Shpall, Shubham Pant, Raghu Kalluri
Faculty, Staff and Students Publications
Oncogenic KRAS is amongst the key genetic drivers for initiation and maintenance of pancreatic ductal adenocarcinoma (PDAC). Here, we show that engineered exosomes with KrasG12D specific siRNA (iExoKrasG12D) reveal a biodistribution in pancreas with negligible toxicity in preclinical studies in mice and Rhesus macaques. Clinical testing of iExoKrasG12D in the iEXPLORE (iExoKrasG12D in Pancreatic Cancer) Phase I study employed a non-randomized single-arm classical 3 + 3 dose escalation design (Phase Ia), followed by an accelerated titration design (Phase Ib) (NCT03608631). The primary outcomes included safety, tolerability and target engagement, and the secondary outcomes aimed to assess disease control. …