Medicine and Health Sciences Commons^™

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 …

Cardiac Surgery For Treatment Of Covid-19-Associated Infectious Endocarditis, Ali Taghizadeh-Waghefi, Asen Petrov, Manuel Wilbring, Konstantin Alexiou, Utz Kappert, Klaus Matschke, Sems-Malte Tugtekin

The Texas Heart Institute Journal

BACKGROUND: Significant uncertainty exists about the optimal timing of surgery for infectious endocarditis (IE) surgery in patients with active SARS-CoV-2 infection. This case series and a systematic review of the literature were carried out to evaluate the timing of surgery and postsurgical outcomes for patients with COVID-19-associated IE.

METHODS: The PubMed database was searched for reports published from June 20, 2020, to June 24, 2021, that contained the terms infective endocarditis and COVID-19. A case series of 8 patients from the authors' facility was also added.

RESULTS: A total of 12 cases were included, including 4 case reports that met …

The Evolution Of Durable, Implantable Axial-Flow Rotary Blood Pumps, P Alex Smith, Yaxin Wang, O H Frazier

The Texas Heart Institute Journal

Left ventricular assist devices (LVADs) are increasingly used to treat patients with end-stage heart failure. Implantable LVADs were initially developed in the 1960s and 1970s. Because of technological constraints, early LVADs had limited durability (eg, membrane or valve failure) and poor biocompatibility (eg, driveline infections and high rates of hemolysis caused by high shear rates). As the technology has improved over the past 50 years, contemporary rotary LVADs have become smaller, more durable, and less likely to result in infection. A better understanding of hemodynamics and end-organ perfusion also has driven research into the enhanced functionality of rotary LVADs. This …

Patterns Of Co-Occurring Birth Defects In Children With Anotia And Microtia, Jeremy M Schraw, Renata H Benjamin, Charles J Shumate, Mark A Canfield, Daryl A Scott, Scott D Mclean, Hope Northrup, Angela E Scheuerle, Christian P Schaaf, Joseph W Ray, Han Chen, A J Agopian, Philip J Lupo

Faculty, Staff and Student Publications

Many infants with anotia or microtia (A/M) have co-occurring birth defects, although few receive syndromic diagnoses in the perinatal period. Evaluation of co-occurring birth defects in children with A/M could identify patterns indicative of undiagnosed/unrecognized syndromes. We obtained information on co-occurring birth defects among infants with A/M for delivery years 1999-2014 from the Texas Birth Defects Registry. We calculated observed-to-expected ratios (OER) to identify birth defect combinations that occurred more often than expected by chance. We excluded children diagnosed with genetic or chromosomal syndromes from analyses. Birth defects and syndromes/associations diagnosed ≤1 year of age were considered. We identified 1310 …

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, …

Egr1 Drives Cell Proliferation By Directly Stimulating Tfeb Transcription In Response To Starvation, Marcella Cesana, Gennaro Tufano, Francesco Panariello, Nicolina Zampelli, Susanna Ambrosio, Rossella De Cegli, Margherita Mutarelli, Lorenzo Vaccaro, Micheal J Ziller, Davide Cacchiarelli, Diego L Medina, Andrea Ballabio

Duncan NRI Faculty and Staff Publications

The stress-responsive transcription factor EB (TFEB) is a master controller of lysosomal biogenesis and autophagy and plays a major role in several cancer-associated diseases. TFEB is regulated at the posttranslational level by the nutrient-sensitive kinase complex mTORC1. However, little is known about the regulation of TFEB transcription. Here, through integrative genomic approaches, we identify the immediate-early gene EGR1 as a positive transcriptional regulator of TFEB expression in human cells and demonstrate that, in the absence of EGR1, TFEB-mediated transcriptional response to starvation is impaired. Remarkably, both genetic and pharmacological inhibition of EGR1, using the MEK1/2 inhibitor Trametinib, significantly reduced the …

Parents’ Decision-Making Regarding Whether To Receive Adult-Onset Only Genetic Findings For Their Children: Findings From The Babyseq Project, Stacey Pereira, Amanda M Gutierrez, Jill Oliver Robinson, Kurt D Christensen, Casie A Genetti, Carrie L Blout Zawatsky, Rebecca L Hsu, Bethany Zettler, Melissa Kurtz Uveges, Richard B Parad, Alan H Beggs, Ingrid A Holm, Robert C Green, Amy L Mcguire

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Most professional guidelines recommend against genetic screening for adult-onset only (AO) conditions until adulthood, yet others argue that there may be benefit to disclosing such results. We explored parents' decision-making on this issue in the BabySeq Project, a clinical trial of newborn genomic sequencing.

Methods: We conducted interviews with parents (N = 24) who were given the option to receive actionable AO results for their children. Interviews explored parents' motivations to receive and reasons to decline AO genetic disease risk information, their decision-making process, and their suggestions for supporting parents in making this decision.

Results: Parents noted several motivations …

Long-Chain Polyunsaturated Lipids Associated With Responsiveness To Anti-Pd-1 Therapy Are Colocalized With Immune Infiltrates In The Tumor Microenvironment, Mary E King, Robert Yuan, Jeremy Chen, Komal Pradhan, Isabel Sariol, Shirley Li, Ashish Chakraborty, Oscar Ekpenyong, Jennifer H Yearley, Janica C Wong, Luis Zúñiga, Daniela Tomazela, Maribel Beaumont, Jin-Hwan Han, Livia S Eberlin

Faculty, Staff and Students Publications

The programmed cell death protein-1 (PD-1) is highly expressed on the surface of antigen-specific exhausted T cells and, upon interaction with its ligand PD-L1, can result in inhibition of the immune response. Anti-PD-1 treatment has been shown to extend survival and result in durable responses in several cancers, yet only a subset of patients benefit from this therapy. Despite the implication of metabolic alteration following cancer immunotherapy, mechanistic associations between antitumor responses and metabolic changes remain unclear. Here, we used desorption electrospray ionization mass spectrometry imaging to examine the lipid profiles of tumor tissue from three syngeneic murine models with …

Covid-19 Induced Environments, Health-Related Quality Of Life Outcomes And Problematic Behaviors: Evidence From Children With Syndromic Autism Spectrum Disorders, Corneliu Bolbocean, Kayla B Rhidenour, Maria Mccormack, Bernhard Suter, J Lloyd Holder

Faculty, Staff and Students Publications

Between July 2020 and January 2021, 230 principal caregivers completed a questionnaire to measure proxy-assessed health-related quality of life outcomes (HRQoL), behavioral outcomes in children with syndromic autism spectrum disorders and COVID-19 induced changes to lifestyle and environments. HRQoL and behavioral outcomes reported earlier during the pandemic were generally worse compared to those reported later. COVID-19 induced reduction to a caregiver's mental health appointments, and hours spent watching TV were associated with decreases in HRQoL and increased the likelihood of problematic behaviors. Increasing time outdoors and time away from digital devices were positively associated with HRQoL and behaviors and might …

Child Abuse Pediatrics Research Network: The Capnet Core Data Project, Joanne N Wood, Kristine A Campbell, James D Anderst, Angela N Bachim, Rachel P Berger, Kent P Hymel, Nancy S Harper, Megan M Letson, John D Melville, Oluwatimilehin Okunowo, Daniel M Lindberg

Faculty, Staff and Students Publications

OBJECTIVE: Examine the epidemiology of subspecialty physical abuse evaluations within CAPNET, a multicenter child abuse pediatrics research network.

METHODS: We conducted a cross-sectional study of children(in-person or remote) by a child abuse pediatrician (CAP) due to concerns for physical abuse at ten CAPNET hospital systems from February 2021 through December 2021.

RESULTS: Among 3667 patients with 3721 encounters, 69.4% wereold; 44.3%old, 59.1% male; 27.1% Black; 57.8% White, 17.0% Hispanic; and 71.0 % had public insurance. The highest level of care was outpatient/emergency department in 60.7%, inpatient unit in 28.0% and intensive care in 11.4%. CAPs performed 79.1% in-person consultations and …

Serum Bile Acids As A Prognostic Biomarker In Biliary Atresia Following Kasai Portoenterostomy, Sanjiv Harpavat, Kieran Hawthorne, Kenneth D R Setchell, Monica Narvaez Rivas, Lisa Henn, Charlotte A Beil, Saul J Karpen, Vicky L Ng, Estella M Alonso, Jorge A Bezerra, Stephen L Guthery, Simon Horslen, Kathy M Loomes, Patrick Mckiernan, John C Magee, Robert M Merion, Jean P Molleston, Philip Rosenthal, Richard J Thompson, Kasper S Wang, Ronald J Sokol, Benjamin L Shneider, Childhood Liver Disease Research Network (Children)

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: In biliary atresia, serum bilirubin is commonly used to predict outcomes after Kasai portoenterostomy (KP). Infants with persistently high levels invariably need liver transplant, but those achieving normalized levels have a less certain disease course. We hypothesized that serum bile acid levels could help predict outcomes in the latter group.

APPROACH AND RESULTS: Participants with biliary atresia from the Childhood Liver Disease Research Network were included if they had normalized bilirubin levels 6 months after KP and stored serum samples from the 6-month post-KP clinic visit ( n = 137). Bile acids were measured from the stored …

Novel And Replicated Clinical And Genetic Risk Factors For Toxicity From High-Dose Methotrexate In Pediatric Acute Lymphoblastic Leukemia, Mark Zobeck, M Brooke Bernhardt, Kala Y Kamdar, Karen R Rabin, Philip J Lupo, Michael E Scheurer

Faculty, Staff and Students Publications

STUDY OBJECTIVE: Methotrexate (MTX) is a key component of treatment for high-risk pediatric acute lymphoblastic leukemia (ALL) but may cause acute kidney injury and prolonged hospitalization due to delayed clearance. The purpose of this study is to identify clinical and genetic factors that may predict which children are at risk for creatinine increase and prolonged MTX clearance.

DESIGN: We conducted a single-center, retrospective cohort study of pediatric patients with ALL who received 4000-5000 mg/m

MAIN RESULTS: Hispanic ethnicity, body mass index (BMI) < 3%, BMI between 85%-95%, and Native American genetic ancestry were found to be associated with an increased risk for creatinine elevation. Older age, Black race, and use of the intensive monitoring protocol were associated with a decreased risk for creatinine elevation. Older age, B- compared to T-ALL, and the minor alleles of rs2838958/SLC19A1 and rs7317112/ABCC4 were associated with an increased risk for delayed clearance. Black race, MTX dose reduction, and the minor allele of rs2306283/SLCO1B1 were found to be associated with a decreased risk for delayed clearance.

CONCLUSIONS: These predictors of MTX toxicities may allow for more precise individualized toxicity risk prediction.

Recovery From The Impact Of Covid-19 On Treatment Times And Clinical Outcomes Of Patients With St-Segment Elevation Myocardial Infarction: An Interim Analysis, Abdelrahman Ali, Thomas Schirmer, Francis J Kiernan, Bryan Piccirillo, Joseph Ingrassia, Talhat Azemi, Immad Sadiq, Daniel B Fram, Asad Rizvi, Saurabh Joshi, Jeffrey Mather, Raymond G Mckay

The Texas Heart Institute Journal

BACKGROUND: Previous studies have documented a negative impact of the COVID-19 pandemic on emergent percutaneous treatment of patients with ST-segment elevation myocardial infarction (STEMI), but few have examined recovery of healthcare systems in restoring prepandemic STEMI care.

METHODS: Retrospective analysis was performed of data from 789 patients with STEMI from a large tertiary medical center treated with percutaneous coronary intervention between January 1, 2019, and December 31, 2021.

RESULTS: For patients with STEMI presenting to the emergency department, median time from door to balloon was 37 minutes in 2019, 53 minutes in 2020, and 48 minutes in 2021 (P < .001), whereas median time from first medical contact to device changed from 70 to 82 to 75 minutes, respectively (P = .002). Treatment time changes in 2020 and 2021 correlated with median emergency department evaluation time (30 to 41 to 22 minutes, respectively; P = .001) but not median catheterization laboratory revascularization time. For transfer patients, median time from first medical contact to device changed from 110 to 133 to 118 minutes, respectively (P = .005). In 2020 and 2021, patients with STEMI had greater late presentation (P = .028) and late mechanical complications (P = .021), with nonsignificant increases in yearly in-hospital mortality (3.6% to 5.2% to 6.4%; P = .352).

CONCLUSION: …

Hiv Increases The Risk Of Cigarette Smoke-Induced Emphysema Through Mmp-9, Bashar S. Staitieh, Simran Malik, Sara C. Auld, Gregory W. Wigger, Xian Fan, Andrew T. Roth, Tanima Chatterjee, Itika Arora, S. Vamsee Raju, Sonya Heath, Saurabh Aggrawal

2020-Current year OA Pubs

BACKGROUND: HIV is associated with an increased risk for emphysema. Matrix metalloproteinase 9 (MMP-9) is a lung tissue remodeling enzyme associated with emphysema. We previously found MMP-9 activity increases with increases in oxidative stress and that HIV increases alveolar oxidative stress. We hypothesized that HIV proteins would increase the risk of cigarette smoke-induced emphysema due to MMP-9.

METHODS: HIV-1 transgenic rats and wild-type littermates were exposed to cigarette smoke or sham for 8 weeks. Lung compliance and histology were assessed. Bronchoalveolar lavage (BAL), primary alveolar macrophages (AM), and serum samples were obtained. A rat alveolar macrophage cell line was exposed …

Pulmonary Open, Robotic, And Thoracoscopic Lobectomy (Portal) Study: An Analysis Of 5721 Cases, Michael S. Kent, Bryan Meyers, Et Al.

2020-Current year OA Pubs

OBJECTIVE: The aim of this study was to analyze outcomes of open lobectomy (OL), VATS, and robotic-assisted lobectomy (RL).

SUMMARY BACKGROUND DATA: Robotic-assisted lobectomy has seen increasing adoption for treatment of early-stage lung cancer. Comparative data regarding these approaches is largely from single-institution case series or administrative datasets.

METHODS: Retrospective data was collected from 21 institutions from 2013 to 2019. All consecutive cases performed for clinical stage IA-IIIA lung cancer were included. Neoadjuvant cases were excluded. Propensity-score matching (1:1) was based on age, sex, race, smoking-status, FEV1%, Zubrod score, American Society of Anesthesiologists score, tumor size, and clinical T and …

Determinants And Mechanisms Of The Low Fusogenicity And High Dependence On Endosomal Entry Of Omicron Subvariants, Panke Qu, John P Evans, Chaitanya Kurhade, Cong Zeng, Yi-Min Zheng, Kai Xu, Pei-Yong Shi, Xuping Xie, Shan-Lu Liu

Faculty, Staff and Student Publications

The rapid spread and strong immune evasion of the SARS-CoV-2 Omicron subvariants has raised serious concerns for the global COVID-19 pandemic. These new variants exhibit generally reduced fusogenicity and increased endosomal entry pathway utilization compared to the ancestral D614G variant, the underlying mechanisms of which remain elusive. Here, we show that the C-terminal S1 mutations of the BA.1.1 subvariant, H655Y and T547K, critically govern the low fusogenicity of Omicron. Notably, H655Y also dictates the enhanced endosome entry pathway utilization. Mechanistically, T547K and H655Y likely stabilize the spike trimer conformation as suggested by increased molecular interactions in structural modeling and enhanced …

Li-Rads: Looking Back, Looking Forward, Victoria Chernyak, Kathryn J Fowler, Richard K G Do, Aya Kamaya, Yuko Kono, An Tang, Donald G. Mitchell, Jeffrey Weinreb, Cynthia S Santillan, Claude B Sirlin

Department of Radiology Faculty Papers

Since its initial release in 2011, the Liver Imaging Reporting and Data System (LI-RADS) has evolved and expanded in scope. It started as a single algorithm for hepatocellular carcinoma (HCC) diagnosis with CT or MRI with extracellular contrast agents and has grown into a multialgorithm network covering all major liver imaging modalities and contexts of use. Furthermore, it has developed its own lexicon, report templates, and supplementary materials. This article highlights the major achievements of LI-RADS in the past 11 years, including adoption in clinical care and research across the globe, and complete unification of HCC diagnostic systems in the …

Jaml Immunotherapy Targets Recently Activated Tumor-Infiltrating Cd8+ T Cells, Simon Eschweiler, Alice Wang, Ciro Ramírez-Suástegui, Adrian Von Witzleben, Yingcong Li, Serena J Chee, Hayley Simon, Monalisa Mondal, Matthew Ellis, Gareth J Thomas, Vivek Chandra, Christian H Ottensmeier, Pandurangan Vijayanand

Faculty, Staff and Student Publications

Junctional adhesion molecule-like protein (JAML) serves as a co-stimulatory molecule in γδ T cells. While it has recently been described as a cancer immunotherapy target in mice, its potential to cause toxicity, specific mode of action with regard to its cellular targets, and whether it can be targeted in humans remain unknown. Here, we show that JAML is induced by T cell receptor engagement, reveal that this induction is linked to cis-regulatory interactions between the CD3D and JAML gene loci. When compared with other immunotherapy targets plagued by low target specificity and end-organ toxicity, we find JAML to be mostly …

Prognostic Significance Of Acellular Mucin In Patients Undergoing Cytoreductive Surgery And Hyperthermic Intraperitoneal Chemotherapy (Crs/Hipec) For Appendiceal Neoplasms, Derek J Erstad, Kristen A Robinson, Karen Beaty, Safia Rafeeq, Yi-Ju Chiang, Kanwal Raghav, John P Shen, Michael J Overman, Wai Chin Foo, Melissa W Taggart, Paul F Mansfield, Richard E Royal, Keith F Fournier, Christopher P Scally

Faculty, Staff and Student Publications

Introduction: Appendiceal neoplasms have a propensity for peritoneal dissemination. The standard of care for select individuals is CRS/HIPEC. In the current 8th AJCC Staging system, a finding of only intraperitoneal acellular mucin (M1a) is classified as Stage IVa. There is concern that the current AJCC system may over-stage patients.

Methods: This was a single-institution retrospective review of 164 cases of mucinous appendiceal neoplasm. Patients undergoing CRS/HIPEC with M1a disease were compared to patients with peritoneal deposits containing tumor cells (well-differentiated adenocarcinoma; low-grade mucinous carcinoma peritonei-M1b,G1). Overall and recurrence-free survival were assessed.

Results: Median age was 51 years, 70% were female, …

Recovering False Negatives In Crispr Fitness Screens With Jloe, Merve Dede, Traver Hart

Faculty, Staff and Student Publications

It is widely accepted that pooled library CRISPR knockout screens offer greater sensitivity and specificity than prior technologies in detecting genes whose disruption leads to fitness defects, a critical step in identifying candidate cancer targets. However, the assumption that CRISPR screens are saturating has been largely untested. Through integrated analysis of screen data in cancer cell lines generated by the Cancer Dependency Map, we show that a typical CRISPR screen has a ∼20% false negative rate, in addition to library-specific false negatives. Replicability falls sharply as gene expression decreases, while cancer subtype-specific genes within a tissue show distinct profiles compared …

Clic And Membrane Wound Repair Pathways Enable Pandemic Norovirus Entry And Infection, B Vijayalakshmi Ayyar, Khalil Ettayebi, Wilhelm Salmen, Umesh C Karandikar, Frederick H Neill, Victoria R Tenge, Sue E Crawford, Erhard Bieberich, B V Venkataram Prasad, Robert L Atmar, Mary K Estes

Faculty, Staff and Students Publications

Globally, most cases of gastroenteritis are caused by pandemic GII.4 human norovirus (HuNoV) strains with no approved therapies or vaccines available. The cellular pathways that these strains exploit for cell entry and internalization are unknown. Here, using nontransformed human jejunal enteroids (HIEs) that recapitulate the physiology of the gastrointestinal tract, we show that infectious GII.4 virions and virus-like particles are endocytosed using a unique combination of endosomal acidification-dependent clathrin-independent carriers (CLIC), acid sphingomyelinase (ASM)-mediated lysosomal exocytosis, and membrane wound repair pathways. We found that besides the known interaction of the viral capsid Protruding (P) domain with host glycans, the Shell …

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 …

Virology Under The Microscope-A Call For Rational Discourse, Felicia Goodrum, Carolina Lopez, Sean Whelan, Et Al.

2020-Current year OA Pubs

Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. Despite this long history, the COVID-19 pandemic has brought unprecedented attention to the field of virology. Some of this attention is focused on concern about the safe conduct of research with human pathogens. A small but vocal group of individuals has seized upon these concerns - conflating legitimate questions about safely conducting virus-related research with uncertainties over the origins of SARS-CoV-2. The result has fueled …

Simultaneous Heart-Kidney Transplantation: Balancing Competing Outcomes For Transplant Wait-Listed Patients, Andrew Civitello, Ajith Nair

Faculty, Staff and Students Publications

No abstract provided.

A Fetal Tumor Suppressor Axis Abrogates Mll-Fusion-Driven Acute Myeloid Leukemia, Mohamed Eldeeb, Ouyang Yuan, Nicola Guzzi, Phuong Cao Thi Ngoc, Anna Konturek-Ciesla, Trine A Kristiansen, Sowndarya Muthukumar, Jeffrey Magee, Cristian Bellodi, Joan Yuan, David Bryder

2020-Current year OA Pubs

MLL-rearrangements (MLL-r) are recurrent genetic events in acute myeloid leukemia (AML) and frequently associate with poor prognosis. In infants, MLL-r can be sufficient to drive transformation. However, despite the prenatal origin of MLL-r in these patients, congenital leukemia is very rare with transformation usually occurring postnatally. The influence of prenatal signals on leukemogenesis, such as those mediated by the fetal-specific protein LIN28B, remains controversial. Here, using a dual-transgenic mouse model that co-expresses MLL-ENL and LIN28B, we investigate the impact of LIN28B on AML. LIN28B impedes the progression of MLL-r AML through compromised leukemia-initiating cell activity and suppression of MYB signaling. …

Mucosal And Systemic Neutralizing Antibodies To Norovirus Induced In Infant Mice Orally Inoculated With Recombinant Rotaviruses, Takahiro Kawagishi, Liliana Sánchez-Tacuba, Ningguo Feng, Veronica P Costantini, Ming Tan, Xi Jiang, Kim Y Green, Jan Vinjé, Siyuan Ding, Harry B Greenberg

2020-Current year OA Pubs

Rotaviruses (RVs) preferentially replicate in the small intestine and frequently cause severe diarrheal disease, and the following enteric infection generally induces variable levels of protective systemic and mucosal immune responses in humans and other animals. Rhesus rotavirus (RRV) is a simian RV that was previously used as a human RV vaccine and has been extensively studied in mice. Although RRV replicates poorly in the suckling mouse intestine, infection induces a robust and protective antibody response. The recent availability of plasmid only-based RV reverse genetics systems has enabled the generation of recombinant RVs expressing foreign proteins. However, recombinant RVs have not …

Zika Virus Spreads Through Infection Of Lymph Node-Resident Macrophages, Glennys V Reynoso, Autumn C Holmes, Yael Alippe, Michael S Diamond, Et Al.

2020-Current year OA Pubs

To disseminate through the body, Zika virus (ZIKV) is thought to exploit the mobility of myeloid cells, in particular monocytes and dendritic cells. However, the timing and mechanisms underlying shuttling of the virus by immune cells remains unclear. To understand the early steps in ZIKV transit from the skin, at different time points, we spatially mapped ZIKV infection in lymph nodes (LNs), an intermediary site en route to the blood. Contrary to prevailing hypotheses, migratory immune cells are not required for the virus to reach the LNs or blood. Instead, ZIKV rapidly infects a subset of sessile CD169

Family Physicians' Responses To Personal Protective Equipment Shortages In Four Regions In Canada: A Qualitative Study., Maria Mathews, Dana Ryan, Lindsay Hedden, Julia Lukewich, Emily Gard Marshall, Shabnam Asghari, Amanda Lee Terry, Richard Buote, Leslie Meredith, Lauren Moritz, Sarah Spencer, Judith B. Brown, Erin Christian, Thomas R. Freeman, Paul S. Gill, Shannon L. Sibbald, Eric Wong

Health Studies Publications

BACKGROUND: Despite well-documented increased demands and shortages of personal protective equipment (PPE) during previous disease outbreaks, health systems in Canada were poorly prepared to meet the need for PPE during the COVID-19 pandemic. In the primary care sector, PPE shortages impacted the delivery of health services and contributed to increased workload, fear, and anxiety among primary care providers. This study examines family physicians' (FPs) response to PPE shortages during the first year of the COVID-19 pandemic to inform future pandemic planning.

METHODS: As part of a multiple case study, we conducted semi-structured qualitative interviews with FPs across four regions in …

Analysis Of Acquired Resistance Mechanisms To Osimertinib In Patients With Egfr-Mutated Advanced Non-Small Cell Lung Cancer From The Aura3 Trial, Juliann Chmielecki, Tony Mok, Yi-Long Wu, Ji-Youn Han, Myung-Ju Ahn, Suresh S Ramalingam, Thomas John, Isamu Okamoto, James Chih-Hsin Yang, Frances A Shepherd, Krishna C Bulusu, Gianluca Laus, Barbara Collins, J Carl Barrett, Ryan J Hartmaier, Vassiliki Papadimitrakopoulou

Faculty, Staff and Student Publications

Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), potently and selectively inhibits EGFR-TKI-sensitizing and EGFR T790M resistance mutations. This analysis evaluates acquired resistance mechanisms to second-line osimertinib (n = 78) in patients with EGFR T790M advanced non-small cell lung cancer (NSCLC) from AURA3 (NCT02151981), a randomized phase 3 study comparing osimertinib with chemotherapy. Plasma samples collected at baseline and disease progression/treatment discontinuation are analyzed using next-generation sequencing. Half (50%) of patients have undetectable plasma EGFR T790M at disease progression and/or treatment discontinuation. Fifteen patients (19%) have >1 resistance-related genomic alteration; MET amplification (14/78, 18%) and EGFR C797X mutation …

Impact Of Penicillin Allergy Labels On Children Treated For Outpatient Respiratory Infections, Torsten Joerger, Margaret G Taylor, Yun Li, Debra L Palazzi, Jeffrey S Gerber

Faculty, Staff and Students Publications

BACKGROUND: Penicillin allergy is the most common antibiotic allergy, yet most children labeled as allergic tolerate penicillin. The impact of inaccurate penicillin allergy labels (PALs) on pediatric outpatients is unknown. The objective of this study was to compare outcomes between children with and without a PAL after treatment for outpatient respiratory tract infections (RTI).

METHODS: A retrospective, longitudinal birth cohort study was performed in children who received care in 90 pediatric primary care practices in Philadelphia and Houston metropolitan areas. Prescribing and clinical outcomes of children with a PAL at the time of an RTI were compared to non-allergic children, …