Medical Specialties Commons^™

Umbilical Cord Blood Transplantation: Connecting Its Origin To Its Future, Gabriela Sanchez-Petitto, Katayoun Rezvani, May Daher, Hind Rafei, Partow Kebriaei, Elizabeth J Shpall, Amanda Olson

Faculty, Staff and Student Publications

Transplantation of umbilical cord blood (UCB) is an attractive alternative source of hematopoietic stem cells (HSCs). The unique properties of cord blood and its distinct immune tolerance and engraftment kinetics compared to bone marrow (BM) and peripheral blood progenitor cells, permit a wider disparity in human leukocyte antigen levels between a cord blood donor and recipient after an unrelated umbilical cord blood transplant (UCBT). In addition, it is readily available and has a lowered risk of graft-versus-host disease (GvHD), with similar long-term clinical outcomes, compared to BM transplants. However, the relatively low number of cells administered by UCB units, as …

Taking A Load Off: User Perceptions Of Smart Offloading Walkers For Diabetic Foot Ulcers Using The Technology Acceptance Model, M G Finco, Gozde Cay, Myeounggon Lee, Jason Garcia, Elia Salazar, Tze-Woei Tan, David G Armstrong, Bijan Najafi

Center on Aging Staff Publications

People with diabetic foot ulcers (DFUs) are commonly prescribed offloading walkers, but inadequate adherence to prescribed use can be a barrier to ulcer healing. This study examined user perspectives of offloading walkers to provide insight on ways to help promote adherence. Participants were randomized to wear: (1) irremovable, (2) removable, or (3) smart removable walkers (smart boot) that provided feedback on adherence and daily walking. Participants completed a 15-item questionnaire based on the Technology Acceptance Model (TAM). Spearman correlations assessed associations between TAM ratings with participant characteristics. Chi-squared tests compared TAM ratings between ethnicities, as well as 12-month retrospective fall …

Sleep Duration, Hypnotic Drug Use, And Risk Factors: Cross- Sectional Study, Nazanin Jalali, Parvin Khalili, Zahra Jamali, Zahra Jalali, Amir Moghadam-Ahmadi, Alireza Vakilian, Fatemeh Ayoobi

Department of Neurology Faculty Papers

Both short sleep duration (SSD) and long sleep duration (LSD) are associated with an increased risk of morbidity and mortality. Here, we aimed to assess the prevalence of sleep duration disturbances among adults in association with demographic, medication use, personal habits, and chronic diseases, while also considering the impact of hypnotic drug use. We performed a cross-sectional study of 9991 adult participants of the Rafsanjan Cohort Study (RCS), as part of the Prospective epidemiological research studies in Iran (PERSIAN). Multivariate logistic regression analyses were conducted to assess the association between short (< 6 h) and long (> 9 h) sleep duration with demographic and lifestyle …

In Utero Exposure To Antiemetic And Risk Of Adult-Onset Colorectal Cancer, Caitlin C Murphy, Piera M Cirillo, Nickilou Y Krigbaum, Amit G Singal, Barbara A Cohn

Faculty, Staff and Student Publications

BACKGROUND: Incidence rates of colorectal cancer (CRC) are increasing among adults born in and after the 1960s, implicating pregnancy-related exposures introduced at that time as risk factors. Dicyclomine, an antispasmodic used to treat irritable bowel syndrome, was initially included in Bendectin (comprising doxylamine, pyridoxine, and dicyclomine), an antiemetic prescribed during pregnancy in the 1960s.

METHODS: We estimated the association between in utero exposure to Bendectin and risk of CRC in offspring of the Child Health and Development Studies, a multigenerational cohort that enrolled pregnant women in Oakland, CA, between 1959 and 1966 (n = 14 507 mothers and 18 751 …

Developing A Parsimonious Frailty Index For Older, Multimorbid Adults With Heart Failure Using Machine Learning, Javad Razjouyan, Molly J Horstman, Ariela R Orkaby, Salim S Virani, Orna Intrator, Parag Goyal, Christopher I Amos, Aanand D Naik

Faculty, Staff and Student Publications

Frailty is associated with adverse outcomes in heart failure (HF). A parsimonious frailty index (FI) that predicts outcomes of older, multimorbid patients with HF could be a useful resource for clinicians. A retrospective study of veterans hospitalized from October 2015 to October 2018 with HF, aged ≥50 years, and discharged home developed a 10-item parsimonious FI using machine learning from diagnostic codes, laboratory results, vital signs, and ejection fraction (EF) from outpatient encounters. An unsupervised clustering technique identified 5 FI strata: severely frail, moderately frail, mildly frail, prefrail, and robust. We report hazard ratios (HRs) of mortality, adjusting for age, …

Can Breaking Heroin Addiction Lead To A Broken Heart? A Case Of Reverse Takotsubo Cardiomyopathy In A Patient With Heroin Withdrawal, Hunter Launer, Daniel Nelson, Alarica Dietzen, Atul Singla

The Texas Heart Institute Journal

Reverse takotsubo cardiomyopathy is triggered by emotional or physical stress and has a presentation similar to that of acute coronary syndrome. A 39-year-old woman with a history of heroin use disorder presented with intractable nausea, vomiting, and diarrhea. She was diagnosed with heroin withdrawal and started on buprenorphine-naloxone. On day 2 of her hospitalization, she developed chest heaviness and had an elevated troponin I level of 3.2 ng/mL (reference range, 0.015-0.045 ng/mL); electrocardiography showed new T-wave inversions in the anterior and inferior leads. Emergent coronary angiography showed patent coronary arteries, and left ventriculography showed basal hypokinesis and apical hyperkinesis, consistent …

Association Of Rare Protein-Truncating Dna Variants In Apob Or Pcsk9 With Low-Density Lipoprotein Cholesterol Level And Risk Of Coronary Heart Disease, Jacqueline S Dron, Aniruddh P Patel, Yiyi Zhang, Sean J Jurgens, Dimitri J Maamari, Minxian Wang, Eric Boerwinkle, Alanna C Morrison, Paul S De Vries, Myriam Fornage, Lifang Hou, Donald M Lloyd-Jones, Bruce M Psaty, Russell P Tracy, Joshua C Bis, Ramachandran S Vasan, Daniel Levy, Nancy Heard-Costa, Stephen S Rich, Xiuqing Guo, Kent D Taylor, Richard A Gibbs, Jerome I Rotter, Cristen J Willer, Elizabeth C Oelsner, Andrew E Moran, Gina M Peloso, Pradeep Natarajan, Amit V Khera

Faculty, Staff and Student Publications

IMPORTANCE: Protein-truncating variants (PTVs) in apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9) are associated with significantly lower low-density lipoprotein (LDL) cholesterol concentrations. The association of these PTVs with coronary heart disease (CHD) warrants further characterization in large, multiracial prospective cohort studies.

OBJECTIVE: To evaluate the association of PTVs in APOB and PCSK9 with LDL cholesterol concentrations and CHD risk.

DESIGN, SETTING, AND PARTICIPANTS: This studied included participants from 5 National Heart, Lung, and Blood Institute (NHLBI) studies and the UK Biobank. NHLBI study participants aged 5 to 84 years were recruited between 1971 and 2002 across the …

Types Of Diagnostic Errors Reported By Paediatric Emergency Providers In A Global Paediatric Emergency Care Research Network, Prashant Mahajan, Joseph A Grubenhoff, Jim Cranford, Maala Bhatt, James M Chamberlain, Todd Chang, Mark Lyttle, Rianne Oostenbrink, Damian Roland, Richard M Rudy, Kathy N Shaw, Robert Velasco Zuniga, Apoorva Belle, Nathan Kuppermann, Hardeep Singh

Faculty, Staff and Students Publications

Background: Diagnostic errors, reframed as missed opportunities for improving diagnosis (MOIDs), are poorly understood in the paediatric emergency department (ED) setting. We investigated the clinical experience, harm and contributing factors related to MOIDs reported by physicians working in paediatric EDs.

Methods: We developed a web-based survey in which physicians participating in the international Paediatric Emergency Research Network representing five out of six WHO regions, described examples of MOIDs involving their own or a colleague's patients. Respondents provided case summaries and answered questions regarding harm and factors contributing to the event.

Results: Of 1594 physicians surveyed, 412 (25.8%) responded (mean age=43 …

Building The Foundation For A Community-Generated National Research Blueprint For Inherited Bleeding Disorders: Research Priorities To Transform The Care Of People With Hemophilia, Duc Q Tran, Craig C Benson, Judith A Boice, Meera Chitlur, Amy L Dunn, Miguel A Escobar, Kalpna Gupta, Jill M Johnsen, James Jorgenson, Scott D Martin, Suzanne Martin, Shannon L Meeks, Alfredo A Narvaez, Doris V Quon, Mark T Reding, Ulrike M Reiss, Brittany Savage, Kim Schafer, Bruno Steiner, Courtney Thornburg, Lena M Volland, Annette Von Drygalski

Faculty, Staff and Student Publications

BACKGROUND: Decades of research have transformed hemophilia from severely limiting children's lives to a manageable disorder compatible with a full, active life, for many in high-income countries. The direction of future research will determine whether exciting developments truly advance health equity for all people with hemophilia (PWH). National Hemophilia Foundation (NHF) and American Thrombosis and Hemostasis Network conducted extensive inclusive all-stakeholder consultations to identify the priorities of people with inherited bleeding disorders and those who care for them.

RESEARCH DESIGN AND METHODS: Working group (WG) 1 of the NHF State of the Science Research Summit distilled the community-identified priorities for …

Meniscal And Articular Cartilage Predictors Of Outcome After Revision Acl Reconstruction: A 6-Year Follow-Up Cohort Study, Rick W Wright, Laura J Huston, Amanda K Haas, Jacquelyn S Pennings, Christina R Allen, Daniel E Cooper, Thomas M Deberardino, Warren R Dunn, Brett Brick A Lantz, Kurt P Spindler, Michael J Stuart, John P Albright, Annunziato Ned Amendola, Jack T Andrish, Christopher C Annunziata, Robert A Arciero, Bernard R Bach, Champ L Baker, Arthur R Bartolozzi, Keith M Baumgarten, Jeffery R Bechler, Jeffrey H Berg, Geoffrey A Bernas, Stephen F Brockmeier, Robert H Brophy, Charles A Bush-Joseph, J Brad Butler, John D Campbell, James L Carey, James E Carpenter, Brian J Cole, Jonathan M Cooper, Charles L Cox, R Alexander Creighton, Diane L Dahm, Tal S David, David C Flanigan, Robert W Frederick, Theodore J Ganley, Elizabeth A Garofoli, Charles J Gatt, Steven R Gecha, James Robert Giffin, Sharon L Hame, Jo A Hannafin, Christopher D Harner, Norman Lindsay Harris, Keith S Hechtman, Elliott B Hershman, Rudolf G Hoellrich, David C Johnson, Timothy S Johnson, Morgan H Jones, Christopher C Kaeding, Ganesh V Kamath, Thomas E Klootwyk, Bruce A Levy, C Benjamin Ma, G Peter Maiers, Robert G Marx, Matthew J Matava, Gregory M Mathien, David R Mcallister, Eric C Mccarty, Robert G Mccormack, Bruce S Miller, Carl W Nissen, Daniel F O'Neill, Brett D Owens, Richard D Parker, Mark L Purnell, Arun J Ramappa, Michael A Rauh, Arthur C Rettig, Jon K Sekiya, Kevin G Shea, Orrin H Sherman, James R Slauterbeck, Matthew V Smith, Jeffrey T Spang, Ltc Steven J Svoboda, Timothy N Taft, Joachim J Tenuta, Edwin M Tingstad, Armando F Vidal, Darius G Viskontas, Richard A White, James S Williams, Michelle L Wolcott, Brian R Wolf, James J York

Faculty, Staff and Student Publications

Background: Meniscal and chondral damage is common in the patient undergoing revision anterior cruciate ligament (ACL) reconstruction.

Purpose: To determine if meniscal and/or articular cartilage pathology at the time of revision ACL surgery significantly influences a patient's outcome at 6-year follow-up.

Study design: Cohort study; Level of evidence, 3.

Methods: Patients undergoing revision ACL reconstruction were prospectively enrolled between 2006 and 2011. Data collection included baseline demographics, surgical technique, pathology, treatment, and scores from 4 validated patient-reported outcome instruments: International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and …

Stem Cell Mobilization Yields With Daratumumab- And Lenalidomide-Containing Quadruplet Induction Therapy In Newly Diagnosed Multiple Myeloma: Findings From The Master And Griffin Trials, Saurabh Chhabra, Natalie Callander, Nicole L Watts, Luciano J Costa, Bicky Thapa, Jonathan L Kaufman, Jacob Laubach, Douglas W Sborov, Brandi Reeves, Cesar Rodriguez, Ajai Chari, Rebecca Silbermann, Larry D Anderson, Susan Bal, Binod Dhakal, Nitya Nathwani, Nina Shah, Eva Medvedova, Naresh Bumma, Sarah A Holstein, Caitlin Costello, Andrzej Jakubowiak, Tanya M Wildes, Timothy Schmidt, Robert Z Orlowski, Kenneth H Shain, Andrew J Cowan, Bhagirathbhai Dholaria, R Frank Cornell, James H Jerkins, Huiling Pei, Annelore Cortoos, Sharmila Patel, Thomas S Lin, Saad Z Usmani, Paul G Richardson, Peter M Voorhees

Faculty, Staff and Student Publications

For eligible patients with newly diagnosed multiple myeloma (NDMM), standard of care includes induction therapy followed by autologous stem cell transplantation (ASCT). Daratumumab as monotherapy and in combination treatment is approved across multiple lines of therapy for multiple myeloma (MM), and lenalidomide is an effective and commonly used agent for induction and maintenance therapy in MM. However, there is concern that lenalidomide and daratumumab given as induction therapy might impair mobilization of stem cells for ASCT. Therefore, we assessed stem cell mobilization in patients following frontline induction therapy in the MASTER and GRIFFIN phase 2 clinical studies by examining stem …

Electrophysiological Normative Responses To Emotional, Neutral, And Cigarette-Related Images, Francesco Versace, Nicola Sambuco, Menton M Deweese, Paul M Cinciripini

Faculty, Staff and Student Publications

To create reproducible emotional probes, affective scientists rely on sets of standardized pictures that are normed using subjective ratings of valence and emotional arousal. However, when emotional responses are investigated using neurophysiological measures, it might be more appropriate to select pictures integrating information from normative subjective reports and normative neurophysiological responses. Here, we provide electrophysiological normative responses for 323 emotional pictures (215 from the IAPS) covering a wide range of categories (erotica, romantic, appetizing foods, landscapes, people engaged in mundane activities, household objects, disgusting objects, accidents, sad people, violence, mutilations, and cigarette-related contents). Event-related potentials (ERPs) and subjective ratings of …

Racial And Ethnic Disparities In Acute Care Utilization Among Patients With Glomerular Disease, Jill R Krissberg, Michelle M O'Shaughnessy, Abigail R Smith, Margaret E Helmuth, Salem Almaani, Diego H Aviles, Kaye E Brathwaite, Yi Cai, Daniel Cattran, Rasheed Gbadegesin, Dorey A Glenn, Larry A Greenbaum, Sandra Iragorri, Koyal Jain, Myda Khalid, Jason Kidd, Jeffrey Kopp, Richard Lafayette, Jerome C Lane, Francesca Lugani, Jordan G Nestor, Rulan S Parekh, Kimberly Reidy, David T Selewski, Christine B Sethna, C John Sperati, Katherine Tuttle, Katherine Twombley, Tetyana L Vasylyeva, Donald J Weaver, Scott E Wenderfer, Keisha Gibson

Faculty, Staff and Student Publications

RATIONALE & OBJECTIVE: The effects of race, ethnicity, socioeconomic status (SES), and disease severity on acute care utilization in patients with glomerular disease are unknown.

STUDY DESIGN: Prospective cohort study.

SETTING & PARTICIPANTS: 1,456 adults and 768 children with biopsy-proven glomerular disease enrolled in the Cure Glomerulonephropathy (CureGN) cohort.

EXPOSURE: Race and ethnicity as a participant-reported social factor.

OUTCOME: Acute care utilization defined as hospitalizations or emergency department visits.

ANALYTICAL APPROACH: Multivariable recurrent event proportional rate models were used to estimate associations between race and ethnicity and acute care utilization.

RESULTS: Black or Hispanic participants had lower SES and more …

Medicaid Expansion And Postoperative Mortality In Women With Gynecologic Cancer: A Difference-In-Difference Analysis, Sarah P Huepenbecker, Shuangshuang Fu, Charlotte C Sun, Hui Zhao, Kristin M Primm, Sharon H Giordano, Larissa A Meyer

Faculty, Staff and Student Publications

BACKGROUND: The association between Medicaid expansion and postoperative mortality after surgery for gynecologic cancer is unknown. Our objective was to compare 30- and 90-day postoperative mortality after gynecologic cancer surgery before and after 2014 in states that did and did not expand Medicaid.

METHODS: We searched the National Cancer Database for women aged 40-64 years old between 2010 and 2016 who underwent surgery for a primary gynecologic malignancy. We used pre/post and quasi-experimental difference-in-difference (DID) multivariable logistic regressions to evaluate mortality pre-2014 (2010-2013) and post-2014 (2014-2016) for states that did and did not expand Medicaid in January 2014. We completed …

Frontline Combination Of Ponatinib And Hyper-Cvad In Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: 80-Months Follow-Up Results, Hagop Kantarjian, Nicholas J Short, Nitin Jain, Koji Sasaki, Xuelin Huang, Fadi G Haddad, Issa Khouri, Courtney D Dinardo, Naveen Pemmaraju, William Wierda, Guillermo Garcia-Manero, Partow Kebriaei, Rebecca Garris, Sanam Loghavi, Jeffrey Jorgensen, Monica Kwari, Susan O'Brien, Farhad Ravandi, Elias Jabbour

Faculty, Staff and Student Publications

Background:

The combination of ponatinib, a third generation BCR::ABL1 tyrosine kinase inhibitor (TKI), with Hyper-CVAD chemotherapy resulted in high rates of complete molecular remissions and survival, without the need for SCT in most patients with Philadelphia chromosome(Ph)-positive acute lymphocytic leukemia (ALL). Confirming these results in a large cohort of patients followed with longer follow-up would establish this regimen as a new standard of care.

Methods:

Adults with newly diagnosed Ph-positive ALL were treated with the Hyper-CVAD regimen. Ponatinib was added as 45 mg daily x 14 during induction, then 45 mg daily continuously (first 37 patients) or 30 mg daily …

Clinical Outcomes Of Combined Cervical And Transthoracic Surgical Approaches In Patients With Advanced Thyroid Cancer, Jared A Shenson, Mark E Zafereo, Mark Lee, Kevin J Contrera, Lei Feng, Mongkol Boonsripitayanon, Neil Gross, Ryan Goepfert, Anastasios Maniakas, Jennifer Rui Wang, Libby Grubbs, Ara Vaporciyan, Wayne Hofstetter, Stephen Swisher, Reza Mehran, David Rice, Boris Sepesi, Mara Antonoff, Maria Cabanillas, Naifa Busaidy, Ramona Dadu, Natalie L Silver

Faculty, Staff and Student Publications

Background: Advanced thyroid disease involving the mediastinum may be managed surgically with a combined transcervical and transthoracic approach. Contemporary analysis of this infrequently encountered cohort will aid the multidisciplinary team in personalizing treatment approaches.

Methods: Retrospective review of patients undergoing combined transcervical and transthoracic surgery for thyroid cancer at a single high-volume institution from 1994 to 2015.

Results: Thirty-eight patients with median age 59 years (range 28-76) underwent surgery without perioperative mortality. Most patients had primary disease. A majority had distant metastases outside the mediastinum but had locoregionally curable disease. Common complications were temporary (39%) and permanent (18%) hypoparathyroidism, and …

Volume Of Subcortical Brain Regions In Social Anxiety Disorder: Mega-Analytic Results From 37 Samples In The Enigma-Anxiety Working Group, Nynke A Groenewold, Janna Marie Bas-Hoogendam, Alyssa R Amod, Max A Laansma, Laura S Van Velzen, Moji Aghajani, Kevin Hilbert, Hyuntaek Oh, Ramiro Salas, Andrea P Jackowski, Pedro M Pan, Giovanni A Salum, James R Blair, Karina S Blair, Joy Hirsch, Spiro P Pantazatos, Franklin R Schneier, Ardesheer Talati, Karin Roelofs, Inge Volman, Laura Blanco-Hinojo, Narcís Cardoner, Jesus Pujol, Katja Beesdo-Baum, Christopher R K Ching, Sophia I Thomopoulos, Andreas Jansen, Tilo Kircher, Axel Krug, Igor Nenadić, Frederike Stein, Udo Dannlowski, Dominik Grotegerd, Hannah Lemke, Susanne Meinert, Alexandra Winter, Michael Erb, Benjamin Kreifelts, Qiyong Gong, Su Lui, Fei Zhu, Benson Mwangi, Jair C Soares, Mon-Ju Wu, Ali Bayram, Mesut Canli, Raşit Tükel, P Michiel Westenberg, Alexandre Heeren, Henk R Cremers, David Hofmann, Thomas Straube, Alexander G G Doruyter, Christine Lochner, Jutta Peterburs, Marie-José Van Tol, Raquel E Gur, Antonia N Kaczkurkin, Bart Larsen, Theodore D Satterthwaite, Courtney A Filippi, Andrea L Gold, Anita Harrewijn, André Zugman, Robin Bülow, Hans J Grabe, Henry Völzke, Katharina Wittfeld, Joscha Böhnlein, Katharina Dohm, Harald Kugel, Elisabeth Schrammen, Peter Zwanzger, Elisabeth J Leehr, Lisa Sindermann, Tali M Ball, Gregory A Fonzo, Martin P Paulus, Alan Simmons, Murray B Stein, Heide Klumpp, K Luan Phan, Tomas Furmark, Kristoffer N T Månsson, Amirhossein Manzouri, Suzanne N Avery, Jennifer Urbano Blackford, Jacqueline A Clauss, Brandee Feola, Jennifer C Harper, Chad M Sylvester, Ulrike Lueken, Dick J Veltman, Anderson M Winkler, Neda Jahanshad, Daniel S Pine, Paul M Thompson, Dan J Stein, Nic J A Van Der Wee

Faculty, Staff and Student Publications

There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven …

Cognitive-Behavioral Therapy For Obsessive-Compulsive Disorder, Samuel D Spencer, Jordan T Stiede, Andrew D Wiese, Wayne K Goodman, Andrew G Guzick, Eric A Storch

Faculty, Staff and Students Publications

Obsessive-compulsive disorder (OCD) is characterized by the presence of debilitating obsessions and compulsions. Cognitive and behavioral models of OCD provide a strong theoretic and empirical foundation for informing effective psychotherapeutic treatment. Cognitive-behavioral therapy (CBT) for OCD, which includes a deliberate emphasis on exposure and response/ritual prevention, has consistently demonstrated robust efficacy for the treatment of pediatric and adult OCD and is the front-line psychotherapeutic treatment for OCD. Two case vignettes describing CBT for OCD in practice as well as recommendations for clinicians are provided.

Brain Ageing In Schizophrenia: Evidence From 26 International Cohorts Via The Enigma Schizophrenia Consortium, Constantinos Constantinides, Laura K M Han, Clara Alloza, Linda Antonella Antonucci, Celso Arango, Rosa Ayesa-Arriola, Nerisa Banaj, Alessandro Bertolino, Stefan Borgwardt, Jason Bruggemann, Juan Bustillo, Oleg Bykhovski, Vince Calhoun, Vaughan Carr, Stanley Catts, Young-Chul Chung, Benedicto Crespo-Facorro, Covadonga M Díaz-Caneja, Gary Donohoe, Stefan Du Plessis, Jesse Edmond, Stefan Ehrlich, Robin Emsley, Lisa T Eyler, Paola Fuentes-Claramonte, Foivos Georgiadis, Melissa Green, Amalia Guerrero-Pedraza, Minji Ha, Tim Hahn, Frans A Henskens, Laurena Holleran, Stephanie Homan, Philipp Homan, Neda Jahanshad, Joost Janssen, Ellen Ji, Stefan Kaiser, Vasily Kaleda, Minah Kim, Woo-Sung Kim, Matthias Kirschner, Peter Kochunov, Yoo Bin Kwak, Jun Soo Kwon, Irina Lebedeva, Jingyu Liu, Patricia Mitchie, Stijn Michielse, David Mothersill, Bryan Mowry, Víctor Ortiz-García De La Foz, Christos Pantelis, Giulio Pergola, Fabrizio Piras, Edith Pomarol-Clotet, Adrian Preda, Yann Quidé, Paul E Rasser, Kelly Rootes-Murdy, Raymond Salvador, Marina Sangiuliano, Salvador Sarró, Ulrich Schall, André Schmidt, Rodney J Scott, Pierluigi Selvaggi, Kang Sim, Antonin Skoch, Gianfranco Spalletta, Filip Spaniel, Sophia I Thomopoulos, David Tomecek, Alexander S Tomyshev, Diana Tordesillas-Gutiérrez, Therese Van Amelsvoort, Javier Vázquez-Bourgon, Daniela Vecchio, Aristotle Voineskos, Cynthia S Weickert, Thomas Weickert, Paul M Thompson, Lianne Schmaal, Theo G M Van Erp, Jessica Turner, James H Cole, Enigma Schizophrenia Consortium, Danai Dima, Esther Walton

Faculty, Staff and Students Publications

Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18–72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18–73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on …

Electronic Health Records' Support For Primary Care Physicians' Situation Awareness: A Metanarrative Review, April Savoy, Himalaya Patel, Daniel R Murphy, Ashley N D Meyer, Jennifer Herout, Hardeep Singh

Faculty, Staff and Students Publications

OBJECTIVE: Situation awareness (SA) refers to people's perception and understanding of their dynamic environment. In primary care, reduced SA among physicians increases errors in clinical decision-making and, correspondingly, patients' risk of experiencing adverse outcomes. Our objective was to understand the extent to which electronic health records (EHRs) support primary care physicians (PCPs)' SA during clinical decision-making.

METHOD: We conducted a metanarrative review of papers in selected academic databases, including CINAHL and MEDLINE. Eligible studies included original peer-reviewed research published between January 2012 and August 2020 on PCP-EHR interactions. We iteratively queried, screened, and summarized literature focused on EHRs supporting PCPs' …

Transcatheter Aortic Valve-In-Valve-In-Valve Replacement In A Young Woman With Transcatheter Structural Valve Deterioration Within A Degenerated Aortic Root Homograft, Jonathan C Hong, Vicente Orozco-Sevilla, Jose G Diez, Joseph S Coselli

Faculty, Staff and Students Publications

Transcatheter aortic valve replacement is a well-established procedure for older patients with symptomatic, severe aortic stenosis. However, data are lacking on its durability and long-term complications, particularly in young patients and patients treated for aortic valve regurgitation. This article describes the case of a 27-year-old woman with complex congenital cardiovascular disease who, after 4 previous aortic valve replacement procedures, presented with structural deterioration of her most recent replacement valve, which had been placed by transcatheter aortic valve replacement inside a failed aortic root homograft 6 years earlier. After the patient had undergone this transcatheter aortic valve replacement procedure to treat …

Higher Doses Of Tisagenlecleucel Are Associated With Improved Outcomes: A Report From The Pediatric Real-World Car Consortium., Heather E. Stefanski, Anne Eaton, Christina Baggott, Jenna Rossoff, Michael R. Verneris, Snehit Prabhu, Holly L. Pacenta, Christine L. Phillips, Julie-An Talano, Amy Moskop, Steven P. Margossian, Douglas Myers, Nicole A. Karras, Patrick A. Brown, Muna Qayed, Michelle Hermiston, Prakash Satwani, M Christa Krupski, Amy K. Keating, Rachel Wilcox, Cara A. Rabik, Vanessa A. Fabrizio, Vasant Chinnabhandar, A Yasemin Goksenin, Kevin J. Curran, Crystal L. Mackall, Theodore W. Laetsch, Liora M. Schultz

Manuscripts, Articles, Book Chapters and Other Papers

Remarkable complete response rates have been shown with tisagenlecleucel, a chimeric antigen receptor (CAR) T-cell therapy targeting CD19, in patients up to age 26 years with refractory/relapsed B-cell acute lymphoblastic leukemia; it is US Food and Drug Administration approved for this indication. Currently, patients receive a single dose of tisagenlecleucel across a wide dose range of 0.2 to 5.0 × 106 and 0.1 to 2.5 × 108 CAR T cells per kg for patients ≤50 and >50 kg, respectively. The effect of cell dose on survival and remission is not yet well established. Our primary goal was to determine if …

Improved Survival After Liver Transplantation For Patients With Human Immunodeficiency Virus (Hiv) And Hiv/Hepatitis C Virus Coinfection In The Integrase Strand Transfer Inhibitor And Direct-Acting Antiviral Eras, Jake Sheraj Jacob, Anjiya Shaikh, Karthik Goli, Nicole E Rich, Jihane N Benhammou, Aijaz Ahmed, Donghee Kim, Abbas Rana, John A Goss, Susanna Naggie, Tzu-Hao Lee, Fasiha Kanwal, George Cholankeril

Faculty, Staff and Students Publications

BACKGROUND: People with human immunodeficiency virus (HIV) with and without hepatitis C virus (HCV) coinfection had poor outcomes after liver transplant (LT). Integrase strand transfer inhibitors (INSTIs) and direct-acting antivirals (DAAs) have changed the treatment landscape for HIV and HCV, respectively, but their impact on LT outcomes remains unclear.

METHODS: This retrospective analysis of adults with HIV monoinfection (n = 246) and HIV/HCV coinfection (n = 286) who received LT compared mortality in patients with HIV who received LT before versus after approval of INSTIs and in patients with HIV/HCV coinfection who received LT before versus after approval of DAAs. …

Using Artificial Intelligence To Improve Pain Assessment And Pain Management: A Scoping Review, Meina Zhang, Linzee Zhu, Shih-Yin Lin, Keela Herr, Chih-Lin Chi, Ibrahim Demir, Karen Dunn Lopez, Nai-Ching Chi

Faculty, Staff and Student Publications

CONTEXT: Over 20% of US adults report they experience pain on most days or every day. Uncontrolled pain has led to increased healthcare utilization, hospitalization, emergency visits, and financial burden. Recognizing, assessing, understanding, and treating pain using artificial intelligence (AI) approaches may improve patient outcomes and healthcare resource utilization. A comprehensive synthesis of the current use and outcomes of AI-based interventions focused on pain assessment and management will guide the development of future research.

OBJECTIVES: This review aims to investigate the state of the research on AI-based interventions designed to improve pain assessment and management for adult patients. We also …

A Phase 1 Study To Evaluate The Safety, Pharmacology, And Feasibility Of Continuous Infusion Nelarabine In Patients With Relapsed And/Or Refractory Lymphoid Malignancies, Prajwal C Boddu, Jayastu Senapati, Farhad Ravandi-Kashani, Elias J Jabbour, Nitin Jain, Mary Ayres, Yuling Chen, Michael J Keating, Hagop M Kantarjian, Varsha Gandhi, Tapan M Kadia

Faculty, Staff and Student Publications

Background: Nelarabine is a purine nucleoside analogue prodrug approved for the treatment of relapsed and refractory T-cell acute lymphoblastic leukemia (R/R T-ALL) and lymphoblastic lymphoma (T-LBL). Although effective in R/R T-ALL, significant neurotoxicity is dose-limiting and such neurotoxicity associated with nucleoside analogues can be related to dosing schedule.

Methods: The authors conducted a phase 1 study to evaluate the pharmacokinetics and toxicity of nelarabine administered as a continuous infusion (CI) for 5 days (120 hours), rather than the standard, short-infusion approach.

Results: Twenty-nine patients with R/R T-ALL/LBL or T-cell prolymphocytic leukemia (T-PLL) were treated, with escalating doses of nelarabine from …

Influence Of County-Level Geographic/Ancestral Origin On Glioma Incidence And Outcomes In Us Hispanics, Kyle M Walsh, Corey Neff, Melissa L Bondy, Carol Kruchko, Jason T Huse, Christopher I Amos, Jill S Barnholtz-Sloan, Quinn T Ostrom

Faculty, Staff and Student Publications

BACKGROUND: Glioma incidence is 25% lower in Hispanics than White non-Hispanics. The US Hispanic population is diverse, and registry-based analyses may mask incidence differences associated with geographic/ancestral origins.

METHODS: County-level glioma incidence data in Hispanics were retrieved from the Central Brain Tumor Registry of the United States. American Community Survey data were used to determine the county-level proportion of the Hispanic population of Mexican/Central American and Caribbean origins. Age-adjusted incidence rate ratios and incidence rate ratios (IRRs) quantified the glioma incidence differences across groups. State-level estimates of admixture in Hispanics were obtained from published 23andMe data.

RESULTS: Compared to predominantly …

Depatuxizumab Mafodotin In Egfr-Amplified Newly Diagnosed Glioblastoma: A Phase Iii Randomized Clinical Trial, Andrew B Lassman, Stephanie L Pugh, Tony J C Wang, Kenneth Aldape, Hui K Gan, Matthias Preusser, Michael A Vogelbaum, Erik P Sulman, Minhee Won, Peixin Zhang, Golnaz Moazami, Marian S Macsai, Mark R Gilbert, Earle E Bain, Vincent Blot, Peter J Ansell, Suvajit Samanta, Madan G Kundu, Terri S Armstrong, Jeffrey S Wefel, Clemens Seidel, Filip Y De Vos, Sigmund Hsu, Andrés F Cardona, Giuseppe Lombardi, Dmitry Bentsion, Richard A Peterson, Craig Gedye, Véronique Bourg, Antje Wick, Walter J Curran, Minesh P Mehta

Faculty, Staff and Student Publications

BACKGROUND: Approximately 50% of newly diagnosed glioblastomas (GBMs) harbor epidermal growth factor receptor gene amplification (EGFR-amp). Preclinical and early-phase clinical data suggested efficacy of depatuxizumab mafodotin (depatux-m), an antibody-drug conjugate comprised of a monoclonal antibody that binds activated EGFR (overexpressed wild-type and EGFRvIII-mutant) linked to a microtubule-inhibitor toxin in EGFR-amp GBMs.

METHODS: In this phase III trial, adults with centrally confirmed, EGFR-amp newly diagnosed GBM were randomized 1:1 to radiotherapy, temozolomide, and depatux-m/placebo. Corneal epitheliopathy was treated with a combination of protocol-specified prophylactic and supportive measures. There was 85% power to detect a hazard ratio (HR) ≤0.75 for overall survival …

Association Between Characteristics Of National Association Of Epilepsy Centers And Reported Utilization Of Specific Surgical Techniques, Kristen H Arredondo, Stephanie M Ahrens, Anto I Bagić, Shasha Bai, Kevin E Chapman, Michael A Ciliberto, Dave F Clarke, Mariah Eisner, Nathan B Fountain, Jay R Gavvala, M Scott Perry, Kyle C Rossi, Lily C Wong-Kisiel, Susan T Herman, Adam P Ostendorf, Naec Center Director Study Group

Faculty, Staff and Student Publications

Background and Objective

Nearly one-third of persons with epilepsy will continue having seizures despite trialing multiple antiseizure medications. Epilepsy surgery may be beneficial in these cases, and evaluation at a comprehensive epilepsy center is recommended. Numerous palliative and potentially curative approaches exist, and types of surgery performed may be influenced by center characteristics. This article describes epilepsy center characteristics associated with epilepsy surgery access and volumes in the United States.

Methods

We analyzed National Association of Epilepsy Centers 2019 annual report and supplemental survey data obtained with responses from 206 adult epilepsy center directors and 136 pediatric epilepsy center directors …

N-Of-1 Trials Vs Usual Care In Children With Hypertension: A Pilot Randomized Clinical Trial, Joyce P Samuel, Cynthia S Bell, Joshua A Samuels, Celin Rajan, Adrienne K Walton, Charles Green, Jon E Tyson

Faculty, Staff and Student Publications

BACKGROUND: Blood pressure (BP) is often inadequately controlled in children treated for hypertension, and personalized (n-of-1) trials show promise for tailoring treatment choices. We assessed whether patients whose treatment choices are informed by an n-of-1 trial have improved BP control compared to usual care.

METHODS: A randomized clinical trial was conducted in a pediatric hypertension clinic in Houston from April 2018 to September 2020. Hypertensive adolescents and young adults 10-22 years old were randomized 1:1 to a strategy of n-of-1 trial using ambulatory BP monitoring to inform treatment choice or usual care, with treatment selected by physician preference. The primary …

Phase Ib Study Of Telisotuzumab Vedotin In Combination With Erlotinib In Patients With C-Met Protein-Expressing Non-Small-Cell Lung Cancer, D Ross Camidge, Fabrice Barlesi, Jonathan W Goldman, Daniel Morgensztern, Rebecca Heist, Everett Vokes, Alex Spira, Eric Angevin, Wu-Chou Su, David S Hong, John H Strickler, Monica Motwani, Martin Dunbar, Apurvasena Parikh, Elysa Noon, Vincent Blot, Jun Wu, Karen Kelly

Faculty, Staff and Student Publications

Purpose: Overexpression of c-Met protein and epidermal growth factor receptor (EGFR) mutations can co-occur in non-small-cell lung cancer (NSCLC), providing strong rationale for dual targeting. Telisotuzumab vedotin (Teliso-V), a first-in-class antibody-drug conjugate targeting c-Met, has shown a tolerable safety profile and antitumor activity as monotherapy. Herein, we report the results of a phase Ib study (ClinicalTrials.gov identifier: NCT02099058) evaluating Teliso-V plus erlotinib, an EGFR tyrosine kinase inhibitor (TKI), in patients with c-Met-positive (+) NSCLC.

Patients and methods: This study evaluated Teliso-V (2.7 mg/kg once every 21 days) plus erlotinib (150 mg once daily) in adult patients (age …