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Full-Text Articles in Medical Specialties

Using Individual Collector Blood Culture Volume Data To Improve Fill Volume, Richard S. Kirby, Jenna M. Meloni, Karishma B. Naik, Matthew D. Minnear, Matthew A. Pettengill Jul 2023

Using Individual Collector Blood Culture Volume Data To Improve Fill Volume, Richard S. Kirby, Jenna M. Meloni, Karishma B. Naik, Matthew D. Minnear, Matthew A. Pettengill

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.


Outpatient Sexually Transmitted Infection Testing And Treatment Patterns In The United States: A Real-World Database Study, Rebecca Lillis, Louis Kuritzky, Zune Huynh, Rodney Arcenas, Avneet Hansra, Roma Shah, Baiyu Yang, Stephanie N. Taylor Jul 2023

Outpatient Sexually Transmitted Infection Testing And Treatment Patterns In The United States: A Real-World Database Study, Rebecca Lillis, Louis Kuritzky, Zune Huynh, Rodney Arcenas, Avneet Hansra, Roma Shah, Baiyu Yang, Stephanie N. Taylor

School of Medicine Faculty Publications

Background: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the most common notifiable sexually transmitted infections (STIs) in the United States. Because symptoms of these infections often overlap with other urogenital infections, misdiagnosis and incorrect treatment can occur unless appropriate STI diagnostic testing is performed in clinical settings. The objective of this study was to describe STI diagnostic testing and antimicrobial treatment patterns and trends among adolescent and adult men and women with lower genitourinary tract symptoms (LGUTS). Methods: We analyzed insurance claims data from the IBM® MarketScan® Research Databases. Patients included were between 14 and 64 years old with …


Genomic Landscape Of Down Syndrome-Associated Acute Lymphoblastic Leukemia, Zhenhua Li, Ti-Cheng Chang, Jacob J Junco, Meenakshi Devidas, Yizhen Li, Wenjian Yang, Xin Huang, Dale J Hedges, Zhongshan Cheng, Mary Shago, Andrew J Carroll, Nyla A Heerema, Julie Gastier-Foster, Brent L Wood, Michael J Borowitz, Lauren Sanclemente, Elizabeth A Raetz, Stephen P Hunger, Eleanor Feingold, Tracie C Rosser, Stephanie L Sherman, Mignon L Loh, Charles G Mullighan, Jiyang Yu, Gang Wu, Philip J Lupo, Karen R Rabin, Jun J Yang Jul 2023

Genomic Landscape Of Down Syndrome-Associated Acute Lymphoblastic Leukemia, Zhenhua Li, Ti-Cheng Chang, Jacob J Junco, Meenakshi Devidas, Yizhen Li, Wenjian Yang, Xin Huang, Dale J Hedges, Zhongshan Cheng, Mary Shago, Andrew J Carroll, Nyla A Heerema, Julie Gastier-Foster, Brent L Wood, Michael J Borowitz, Lauren Sanclemente, Elizabeth A Raetz, Stephen P Hunger, Eleanor Feingold, Tracie C Rosser, Stephanie L Sherman, Mignon L Loh, Charles G Mullighan, Jiyang Yu, Gang Wu, Philip J Lupo, Karen R Rabin, Jun J Yang

Faculty, Staff and Students Publications

Trisomy 21, the genetic cause of Down syndrome (DS), is the most common congenital chromosomal anomaly. It is associated with a 20-fold increased risk of acute lymphoblastic leukemia (ALL) during childhood and results in distinctive leukemia biology. To comprehensively define the genomic landscape of DS-ALL, we performed whole-genome sequencing and whole-transcriptome sequencing (RNA-Seq) on 295 cases. Our integrated genomic analyses identified 15 molecular subtypes of DS-ALL, with marked enrichment of CRLF2-r, IGH::IGF2BP1, and C/EBP altered (C/EBPalt) subtypes compared with 2257 non-DS-ALL cases. We observed abnormal activation of the CEBPD, CEBPA, and CEBPE genes in 10.5% of DS-ALL cases via a …


Screening For Food Insecurity In A Suburban Pediatric Urgent Care, Rachel Foutz Jul 2023

Screening For Food Insecurity In A Suburban Pediatric Urgent Care, Rachel Foutz

Dissertations

Problem: Screening for Social Determinants of Health (SDOH), including food insecurity (FI) should be done on a regular basis at a child’s pediatrician. Many children in the state of Missouri do not have a pediatrician or do not regularly see their pediatrician and are therefore never being screened for FI.

Methods: This observational descriptive quality improvement (QI) project utilized a prospective observational analysis to implement a voluntary FI screening tool in a pediatric only urgent care. The project sampled pediatric patients aged two days to 21 years of life. All participants were given local resources after completing the screening. The …


Acute Agitation Intervention Tool For Reduction Of Polypharmacy, Brooks J. Propst Jul 2023

Acute Agitation Intervention Tool For Reduction Of Polypharmacy, Brooks J. Propst

Dissertations

Introduction: Patients with behavioral health diagnoses are among the highest risk for
aggression. For pediatric patients with behavioral health needs, urgent treatment is
needed for aggressive behavior, due to the potential unwanted outcomes. The purpose of this Quality Improvement (QI) pilot project was to implement an Acute Agitation Intervention Tool that uses the Broset Violence Checklist (BVC) to guide
pharmacological intervention for mild and moderate to severe agitation in pediatric
patients with behavioral health needs ages 8 to 18 to decrease the number of medications that patients are getting per agitation event over a 12-week period.

Methods: This QI included …


Implementing Obesity Management Guidelines In Rural Primary Care, Taylor Bell Jul 2023

Implementing Obesity Management Guidelines In Rural Primary Care, Taylor Bell

Dissertations

Abstract

Problem: In the United States, obesity is one of the leading causes of death among Americans and rates of obesity continue to rise. Geographic location significantly affects the number of obesity cases, with rural areas being affected more than other locations. Despite this, obesity continues to be undertreated by rural primary care providers.

Method: This quality improvement (QI) pilot project utilized a descriptive, observational design to evaluate the implementation of an evidence-based clinical practice guideline algorithm for obesity management in a rural primary care clinic. An algorithm was implemented on patients aged 18-60 years and with a BMI of …


Improving Postpartum Depression Screening Practices In The Postpartum Setting, Courtney Lynn Cole Jul 2023

Improving Postpartum Depression Screening Practices In The Postpartum Setting, Courtney Lynn Cole

Dissertations

Abstract

Problem: Postpartum Depression (PPD) is frequently undetected in women due to barriers that limit effective recognition and diagnosis. Depression screenings and treatment referrals improve outcomes in the immediate postpartum period. Follow-up methods for positive depression screens are often missed by postpartum care teams.

Methods: A descriptive, observational design was used for this quality improvement project. A formalized depression screening protocol was created to help guide nursing staff on a Postpartum Unit when detecting a positive depression screen. Convenience sampling was utilized and the sample included patients aged 18-45. Data collected throughout this quality improvement project included Edinburgh Postnatal Depression …


Extubation Readiness Test In A Pediatric Cardiac Intensive Care Unit, Mary K. Holyoke Jul 2023

Extubation Readiness Test In A Pediatric Cardiac Intensive Care Unit, Mary K. Holyoke

Dissertations

Extubation Readiness Test in a Pediatric Cardiac Intensive Care Unit

Abstract

Problem: The lack of standard extubation readiness tests (ERTs), that are practiced in pediatric ICUs to monitor extubation readiness, clinicians have the difficult task of weighing the risk versus benefit of extubation. ERTs can aid clinicians in deciphering patients ready to be successfully extubated and have shown to decrease length of mechanical ventilation and decrease extubation failures.

Methods: The quality improvement (QI) project utilized a descriptive observational design to assess the effects of the implementation of an ERT in a pediatric cardiac ICU. This project used a convenience sample …


Effect Of Confusion Assessment Scores On Identifying Delirium In Intensive Care Patients, Kayla Jacobs Jul 2023

Effect Of Confusion Assessment Scores On Identifying Delirium In Intensive Care Patients, Kayla Jacobs

Dissertations

Delirium in intensive care unit (ICU) patients can lead to increased length of stay in the hospital, increased risk of complications, increased polypharmacy, family distress and increased rate of mortality (Vasilevskis et al., 2018). Research has shown that addressing modifiable risk factors can improve survival rate by up to 15%, and routine screening for delirium in ICU patients leads to decreased patient anxiety, reduced in-hospital mortality, early recognition, and treatment of delirium (Krewulak et al., 2021 ; Vasilevskis et al., 2018). This quality improvement project used evidence-based intervention to increase accurate documentation of the confusion assessment method in the ICU …


Community Centred Co-Design Methodology For Designing And Implementing Socio-Behavioural Interventions To Counter Covid-19 Related Misinformation Among Marginalized Population Living In The Squatter Settlements Of Karachi, Pakistan: A Methodology Paper, Rubina Qasim, Waqas Ahmed Farooqui, Atiya Rahman, Rukhsana Haroon, Madiha Saleem, Muhammad Rafique, Fiza Noor, Afifa Ghani, Muhammad Yaqoob, Mohammad Tahir Yousafzai Jul 2023

Community Centred Co-Design Methodology For Designing And Implementing Socio-Behavioural Interventions To Counter Covid-19 Related Misinformation Among Marginalized Population Living In The Squatter Settlements Of Karachi, Pakistan: A Methodology Paper, Rubina Qasim, Waqas Ahmed Farooqui, Atiya Rahman, Rukhsana Haroon, Madiha Saleem, Muhammad Rafique, Fiza Noor, Afifa Ghani, Muhammad Yaqoob, Mohammad Tahir Yousafzai

Community Health Sciences

Background: Misinformation regarding COVID-19 pandemic and vaccination is damaging COVID-19 vaccine trust and acceptance in Low- and Middle-Income Countries (LMIC). Identification of misinformation and designing locally acceptable solutions are needed to improve COVID-19 vaccine acceptance. This study aimed to utilize community-led co-design methodology to evaluate misinformation regarding COVID-19 and develop contextual interventions to address misinformation in a marginalized peri urban slum communities of Landhi town Karachi, Pakistan.
Methods: This study was conducted between January and December 2021, in marginalized peri-urban slum dwellers of Muslimabad Colony, Landhi Town Karachi, Pakistan. We used a community-centred co-design methodology embedded within mixed study design …


A Medicare Physician Fee Schedule Analysis Of Reimbursement Trends In Laryngology From 2000 To 2021, James R. Xu, Robert R. Lorenz, Kathleen M. Mulligan, Todd D. Otteson, Nicole C. Maronian, Paul C. Bryson Jul 2023

A Medicare Physician Fee Schedule Analysis Of Reimbursement Trends In Laryngology From 2000 To 2021, James R. Xu, Robert R. Lorenz, Kathleen M. Mulligan, Todd D. Otteson, Nicole C. Maronian, Paul C. Bryson

Student Scholarship

Objective: The purpose of this study is to characterize Medicare reimbursement trends for laryngology procedures over the last two decades. Methods: This analysis used CMS' Physician Fee Schedule (PFS) Look-Up Tool to determine the reimbursement rate of 48 common laryngology procedures, which were divided into four groups based on their practice setting and clinical use: office-based, airway, voice disorders, and dysphagia. The PFS reports the physician service reimbursement for “facilities” and global reimbursement for “non-facilities”. The annual reimbursement rate for each procedure was averaged across all localities and adjusted for inflation. The compound annual growth rate (CAGR) of each procedure's …


Relative Burden Of Cancer And Noncancer Mortality Among Long-Term Survivors Of Breast, Prostate, And Colorectal Cancer In The Us, Madhav Kc, Jane Fan, Terry Hyslop, Sirad Hassan, Michael Cecchini, Shi-Yi Wang, Andrea Silber, Michael S. Leapman, Ira Leeds, Stephanie B. Wheeler, Lisa P. Spees, Cary P. Gross, Maryam Lustberg, Rachel A. Greenup, Amy C. Justice, Kevin C. Oeffinger, Michaela A. Dinan Jul 2023

Relative Burden Of Cancer And Noncancer Mortality Among Long-Term Survivors Of Breast, Prostate, And Colorectal Cancer In The Us, Madhav Kc, Jane Fan, Terry Hyslop, Sirad Hassan, Michael Cecchini, Shi-Yi Wang, Andrea Silber, Michael S. Leapman, Ira Leeds, Stephanie B. Wheeler, Lisa P. Spees, Cary P. Gross, Maryam Lustberg, Rachel A. Greenup, Amy C. Justice, Kevin C. Oeffinger, Michaela A. Dinan

Kimmel Cancer Center Faculty Papers

IMPORTANCE: Improvements in cancer outcomes have led to a need to better understand long-term oncologic and nononcologic outcomes and quantify cancer-specific vs noncancer-specific mortality risks among long-term survivors.

OBJECTIVE: To assess absolute and relative cancer-specific vs noncancer-specific mortality rates among long-term survivors of cancer, as well as associated risk factors.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included 627 702 patients in the Surveillance, Epidemiology, and End Results cancer registry with breast, prostate, or colorectal cancer who received a diagnosis between January 1, 2003, and December 31, 2014, who received definitive treatment for localized disease and who were alive 5 …


The Building Healthy Eating And Self-Esteem Together For University Students Mobile App To Treat Eating Disorders: User-Centered Research Design And Feasibility Study., Kelsie T. Forbush, Kara A. Christensen Pacella, Marianna L. Thomeczek, Sara R. Gould, Danielle A N Chapa, Brianne N. Richson, Victoria L. Perko, Joseph Ayres, Yiyang Chen, Sonakshi Negi Jul 2023

The Building Healthy Eating And Self-Esteem Together For University Students Mobile App To Treat Eating Disorders: User-Centered Research Design And Feasibility Study., Kelsie T. Forbush, Kara A. Christensen Pacella, Marianna L. Thomeczek, Sara R. Gould, Danielle A N Chapa, Brianne N. Richson, Victoria L. Perko, Joseph Ayres, Yiyang Chen, Sonakshi Negi

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: University students are an at-risk group for the development of eating disorders (EDs); however, many college campuses lack sufficient resources to provide ED specialty care. Students report unique reasons for not seeking ED treatment, including the desire to solve the problem on their own (eg, seeking help from friends, self-medicating, or waiting to see if their problems improve), inability to afford treatment, lack of time to participate in the treatment, fear of seeing their primary care physician, and lack of recognition of their issues as an ED. Mobile health (mHealth) apps may be a cost-effective, helpful adjunctive tool to …


Mettl3-Mediated M6a Modification Of Linc00839 Maintains Glioma Stem Cells And Radiation Resistance By Activating Wnt/Β-Catenin Signaling, Jianxing Yin, Fangshu Ding, Zhangchun Cheng, Xin Ge, Yanhui Li, Ailiang Zeng, Junxia Zhang, Wei Yan, Zhumei Shi, Xu Qian, Yongping You, Zhiliang Ding, Jing Ji, Xiefeng Wang Jul 2023

Mettl3-Mediated M6a Modification Of Linc00839 Maintains Glioma Stem Cells And Radiation Resistance By Activating Wnt/Β-Catenin Signaling, Jianxing Yin, Fangshu Ding, Zhangchun Cheng, Xin Ge, Yanhui Li, Ailiang Zeng, Junxia Zhang, Wei Yan, Zhumei Shi, Xu Qian, Yongping You, Zhiliang Ding, Jing Ji, Xiefeng Wang

Faculty, Staff and Student Publications

Long noncoding RNAs (lncRNAs) are involved in glioma initiation and progression. Glioma stem cells (GSCs) are essential for tumor initiation, maintenance, and therapeutic resistance. However, the biological functions and underlying mechanisms of lncRNAs in GSCs remain poorly understood. Here, we identified that LINC00839 was overexpressed in GSCs. A high level of LINC00839 was associated with GBM progression and radiation resistance. METTL3-mediated m6A modification on LINC00839 enhanced its expression in a YTHDF2-dependent manner. Mechanistically, LINC00839 functioned as a scaffold promoting c-Src-mediated phosphorylation of β-catenin, thereby inducing Wnt/β-catenin activation. Combinational use of celecoxib, an inhibitor of Wnt/β-catenin signaling, greatly sensitized GSCs to …


High Glucose-Upregulated Pd-L1 Expression Through Ras Signaling-Driven Downregulation Of Ptrh1 Leads To Suppression Of T Cell Cytotoxic Function In Tumor Environment, Chenggang Gao, Jiaoshun Chen, Jianwei Bai, Haoxiang Zhang, Yanyi Tao, Shihong Wu, Hehe Li, Heshui Wu, Qiang Shen, Tao Yin Jul 2023

High Glucose-Upregulated Pd-L1 Expression Through Ras Signaling-Driven Downregulation Of Ptrh1 Leads To Suppression Of T Cell Cytotoxic Function In Tumor Environment, Chenggang Gao, Jiaoshun Chen, Jianwei Bai, Haoxiang Zhang, Yanyi Tao, Shihong Wu, Hehe Li, Heshui Wu, Qiang Shen, Tao Yin

School of Graduate Studies Faculty Publications

Background: Nearly 80% of patients with pancreatic cancer suffer from glucose intolerance or diabetes. Pancreatic cancer complicated by diabetes has a more immunosuppressive tumor microenvironment (TME) and is associated with a worse prognosis. The relationship between glucose metabolism and programmed cell death-Ligand 1 (PD-L1) is close and complex. It is important to explore the regulation of high glucose on PD-L1 expression in pancreatic cancer and its effect on infiltrating immune effectors in the tumor microenvironment. Methods: Diabetic murine models (C57BL/6) were used to reveal different immune landscape in euglycemic and hyperglycemic pancreatic tumor microenvironment. Bioinformatics, WB, iRIP [Improved RNA Binding …


A Global Study For Acute Myeloid Leukemia With Rarg Rearrangement, Hong-Hu Zhu, Ya-Zhen Qin, Zhang-Lin Zhang, Yong-Jing Liu, Li-Jun Wen, M James You, Cheng Zhang, Esperanza Such, Hong Luo, Hong-Jian Yuan, Hong-Sheng Zhou, Hong-Xing Liu, Reng Xu, Ji Li, Jian-Hu Li, Jian-Ping Hao, Jie Jin, Liang Yu, Jing-Ying Zhang, Li-Ping Liu, Le-Ping Zhang, Rui-Bin Huang, Shu-Hong Shen, Su-Jun Gao, Wei Wang, Xiao-Jing Yan, Xin-You Zhang, Xin Du, Xiao-Xia Chu, Yan-Fang Yu, Yi Wang, Ying-Chang Mi, Ying Lu, Zhen Cai, Zhan Su, David Christopher Taussig, Suzanne Macmahon, Edward D Ball, Huan-You Wang, John S Welch, C Cameron Yin, Gautam Borthakur, Miguel A Sanz, Hagop M Kantarjian, Jin-Yan Huang, Jiong Hu, Su-Ning Chen Jul 2023

A Global Study For Acute Myeloid Leukemia With Rarg Rearrangement, Hong-Hu Zhu, Ya-Zhen Qin, Zhang-Lin Zhang, Yong-Jing Liu, Li-Jun Wen, M James You, Cheng Zhang, Esperanza Such, Hong Luo, Hong-Jian Yuan, Hong-Sheng Zhou, Hong-Xing Liu, Reng Xu, Ji Li, Jian-Hu Li, Jian-Ping Hao, Jie Jin, Liang Yu, Jing-Ying Zhang, Li-Ping Liu, Le-Ping Zhang, Rui-Bin Huang, Shu-Hong Shen, Su-Jun Gao, Wei Wang, Xiao-Jing Yan, Xin-You Zhang, Xin Du, Xiao-Xia Chu, Yan-Fang Yu, Yi Wang, Ying-Chang Mi, Ying Lu, Zhen Cai, Zhan Su, David Christopher Taussig, Suzanne Macmahon, Edward D Ball, Huan-You Wang, John S Welch, C Cameron Yin, Gautam Borthakur, Miguel A Sanz, Hagop M Kantarjian, Jin-Yan Huang, Jiong Hu, Su-Ning Chen

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) with retinoic acid receptor γ (RARG) rearrangement has clinical, morphologic, and immunophenotypic features similar to classic acute promyelocytic leukemia. However, AML with RARG rearrangement is insensitive to alltrans retinoic acid (ATRA) and arsenic trioxide (ATO) and carries a poor prognosis. We initiated a global cooperative study to define the clinicopathological features, genomic and transcriptomic landscape, and outcomes of AML with RARG rearrangements collected from 29 study groups/institutions worldwide. Thirty-four patients with AML with RARG rearrangements were identified. Bleeding or ecchymosis was present in 18 (54.5%) patients. Morphology diagnosed as M3 and M3v accounted for 73.5% and …


When A Calorie Is Not Just A Calorie: Diet Quality And Timing As Mediators Of Metabolism And Healthy Aging, Maria M Mihaylova, Amandine Chaix, Mirela Delibegovic, Jon J Ramsey, Joseph Bass, Girish Melkani, Rajat Singh, Zheng Chen, William W Ja, Michele Shirasu-Hiza, Mary N Latimer, Julie A Mattison, Anna E Thalacker-Mercer, Vishwa Deep Dixit, Satchidananda Panda, Dudley W Lamming Jul 2023

When A Calorie Is Not Just A Calorie: Diet Quality And Timing As Mediators Of Metabolism And Healthy Aging, Maria M Mihaylova, Amandine Chaix, Mirela Delibegovic, Jon J Ramsey, Joseph Bass, Girish Melkani, Rajat Singh, Zheng Chen, William W Ja, Michele Shirasu-Hiza, Mary N Latimer, Julie A Mattison, Anna E Thalacker-Mercer, Vishwa Deep Dixit, Satchidananda Panda, Dudley W Lamming

Faculty, Staff and Student Publications

An epidemic of obesity has affected large portions of the world, increasing the risk of developing many different age-associated diseases, including cancer, cardiovascular disease, and diabetes. In contrast with the prevailing notion that "a calorie is just a calorie," there are clear differences, within and between individuals, in the metabolic response to different macronutrient sources. Recent findings challenge this oversimplification; calories from different macronutrient sources or consumed at different times of day have metabolic effects beyond their value as fuel. Here, we summarize discussions conducted at a recent NIH workshop that brought together experts in calorie restriction, macronutrient composition, and …


Emt Activates Exocytotic Rabs To Coordinate Invasion And Immunosuppression In Lung Cancer, Guan-Yu Xiao, Xiaochao Tan, Bertha L Rodriguez, Don L Gibbons, Shike Wang, Chao Wu, Xin Liu, Jiang Yu, Mayra E Vasquez, Hai T Tran, Jun Xu, William K Russell, Cara Haymaker, Younghee Lee, Jianjun Zhang, Luisa Solis, Ignacio I Wistuba, Jonathan M Kurie Jul 2023

Emt Activates Exocytotic Rabs To Coordinate Invasion And Immunosuppression In Lung Cancer, Guan-Yu Xiao, Xiaochao Tan, Bertha L Rodriguez, Don L Gibbons, Shike Wang, Chao Wu, Xin Liu, Jiang Yu, Mayra E Vasquez, Hai T Tran, Jun Xu, William K Russell, Cara Haymaker, Younghee Lee, Jianjun Zhang, Luisa Solis, Ignacio I Wistuba, Jonathan M Kurie

Faculty, Staff and Student Publications

Epithelial-to-mesenchymal transition (EMT) underlies immunosuppression, drug resistance, and metastasis in epithelial malignancies. However, the way in which EMT orchestrates disparate biological processes remains unclear. Here, we identify an EMT-activated vesicular trafficking network that coordinates promigratory focal adhesion dynamics with an immunosuppressive secretory program in lung adenocarcinoma (LUAD). The EMT-activating transcription factor ZEB1 drives exocytotic vesicular trafficking by relieving Rab6A, Rab8A, and guanine nucleotide exchange factors from miR-148a-dependent silencing, thereby facilitating MMP14-dependent focal adhesion turnover in LUAD cells and autotaxin-mediated CD8


Undetectable Measurable Residual Disease Is Associated With Improved Outcomes In Aml Irrespective Of Treatment Intensity, Alexandre Bazinet, Tapan Kadia, Nicholas J Short, Gautam Borthakur, Sa A Wang, Wei Wang, Sanam Loghavi, Jeffrey Jorgensen, Keyur Patel, Courtney Dinardo, Naval Daver, Yesid Alvarado, Fadi G Haddad, Sherry Pierce, Graciela Nogueras Gonzalez, Abhishek Maiti, Koji Sasaki, Musa Yilmaz, Philip Thompson, William Wierda, Guillermo Garcia-Manero, Michael Andreeff, Elias Jabbour, Marina Konopleva, Xuelin Huang, Hagop Kantarjian, Farhad Ravandi Jul 2023

Undetectable Measurable Residual Disease Is Associated With Improved Outcomes In Aml Irrespective Of Treatment Intensity, Alexandre Bazinet, Tapan Kadia, Nicholas J Short, Gautam Borthakur, Sa A Wang, Wei Wang, Sanam Loghavi, Jeffrey Jorgensen, Keyur Patel, Courtney Dinardo, Naval Daver, Yesid Alvarado, Fadi G Haddad, Sherry Pierce, Graciela Nogueras Gonzalez, Abhishek Maiti, Koji Sasaki, Musa Yilmaz, Philip Thompson, William Wierda, Guillermo Garcia-Manero, Michael Andreeff, Elias Jabbour, Marina Konopleva, Xuelin Huang, Hagop Kantarjian, Farhad Ravandi

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) can be treated with either high- or low-intensity regimens. Highly sensitive assays for measurable residual disease (MRD) now allow for a more precise assessment of response quality. We hypothesized that treatment (Rx) intensity may not be a key predictor of outcomes, assuming that an optimal response to therapy is achieved. We performed a single-center retrospective study including 635 patients with newly diagnosed AML responding to either intensive cytarabine/anthracycline-based chemotherapy (IA; n = 385) or low-intensity venetoclax-based regimens (LOW + VEN; n = 250) and who had adequate flow cytometry-based MRD testing performed at the time of …


Brentuximab Vedotin After Autologous Transplantation In Pediatric Patients With Relapsed/Refractory Hodgkin Lymphoma, Christopher J Forlenza, Jaclyn Rosenzweig, Audrey Mauguen, Ilia Buhtoiarov, Branko Cuglievan, Hema Dave, Rebecca J Deyell, Jamie E Flerlage, Anna K Franklin, Jennifer Krajewski, Kasey J Leger, Lianna J Marks, Robin E Norris, Martha Pacheco, Faye Willen, Adam Paul Yan, Paul D Harker-Murray, Lisa Giulino-Roth Jul 2023

Brentuximab Vedotin After Autologous Transplantation In Pediatric Patients With Relapsed/Refractory Hodgkin Lymphoma, Christopher J Forlenza, Jaclyn Rosenzweig, Audrey Mauguen, Ilia Buhtoiarov, Branko Cuglievan, Hema Dave, Rebecca J Deyell, Jamie E Flerlage, Anna K Franklin, Jennifer Krajewski, Kasey J Leger, Lianna J Marks, Robin E Norris, Martha Pacheco, Faye Willen, Adam Paul Yan, Paul D Harker-Murray, Lisa Giulino-Roth

Faculty, Staff and Student Publications

Outcomes for children and adolescents with relapsed and refractory Hodgkin lymphoma (HL) are poor, with ∼50% of patients experiencing a subsequent relapse. The anti-CD30 antibody-drug conjugate brentuximab vedotin improved progression-free survival (PFS) when used as consolidation after autologous stem cell transplantation (ASCT) in adults with high-risk relapsed/refractory HL. Data on brentuximab vedotin as consolidative therapy after ASCT in pediatric patients with HL are extremely limited, with data of only 11 patients reported in the literature. We performed a retrospective analysis of 67 pediatric patients who received brentuximab vedotin as consolidation therapy after ASCT for the treatment of relapsed/refractory HL to …


High Throughput Single Cell Long-Read Sequencing Analyses Of Same-Cell Genotypes And Phenotypes In Human Tumors, Cheng-Kai Shiau, Lina Lu, Rachel Kieser, Kazutaka Fukumura, Timothy Pan, Hsiao-Yun Lin, Jie Yang, Eric L Tong, Gahyun Lee, Yuanqing Yan, Jason T Huse, Ruli Gao Jul 2023

High Throughput Single Cell Long-Read Sequencing Analyses Of Same-Cell Genotypes And Phenotypes In Human Tumors, Cheng-Kai Shiau, Lina Lu, Rachel Kieser, Kazutaka Fukumura, Timothy Pan, Hsiao-Yun Lin, Jie Yang, Eric L Tong, Gahyun Lee, Yuanqing Yan, Jason T Huse, Ruli Gao

Faculty, Staff and Student Publications

Single-cell nanopore sequencing of full-length mRNAs transforms single-cell multi-omics studies. However, challenges include high sequencing errors and dependence on short-reads and/or barcode whitelists. To address these, we develop scNanoGPS to calculate same-cell genotypes (mutations) and phenotypes (gene/isoform expressions) without short-read nor whitelist guidance. We apply scNanoGPS onto 23,587 long-read transcriptomes from 4 tumors and 2 cell-lines. Standalone, scNanoGPS deconvolutes error-prone long-reads into single-cells and single-molecules, and simultaneously accesses both phenotypes and genotypes of individual cells. Our analyses reveal that tumor and stroma/immune cells express distinct combination of isoforms (DCIs). In a kidney tumor, we identify 924 DCI genes involved in …


Randomized, Double-Blinded, Placebo-Controlled Trial Of Allogeneic Cord Blood T-Regulatory Cells For Treatment Of Covid-19 Ards, Douglas E Gladstone, Franco D'Alessio, Christopher Howard, Mi-Ae Lyu, Jason R Mock, Kevin W Gibbs, Darryl Abrams, Meixian Huang, Ke Zeng, James P Herlihy, Sergio T Castillo, Roland Bassett, Tara Sadeghi, Simrit Parmar, Christopher R Flowers, Siddhartha Mukherjee, David Schoenfeld, Peter F Thall, Arthur S Slutsky Jul 2023

Randomized, Double-Blinded, Placebo-Controlled Trial Of Allogeneic Cord Blood T-Regulatory Cells For Treatment Of Covid-19 Ards, Douglas E Gladstone, Franco D'Alessio, Christopher Howard, Mi-Ae Lyu, Jason R Mock, Kevin W Gibbs, Darryl Abrams, Meixian Huang, Ke Zeng, James P Herlihy, Sergio T Castillo, Roland Bassett, Tara Sadeghi, Simrit Parmar, Christopher R Flowers, Siddhartha Mukherjee, David Schoenfeld, Peter F Thall, Arthur S Slutsky

Faculty, Staff and Students Publications

No abstract provided.


Author Correction: Drugnomeai Is An Ensemble Machine-Learning Framework For Predicting Druggability Of Candidate Drug Targets, Arwa Raies, Ewa Tulodziecka, James Stainer, Lawrence Middleton, Ryan S Dhindsa, Pamela Hill, Ola Engkvist, Andrew R Harper, Slavé Petrovski, Dimitrios Vitsios Jul 2023

Author Correction: Drugnomeai Is An Ensemble Machine-Learning Framework For Predicting Druggability Of Candidate Drug Targets, Arwa Raies, Ewa Tulodziecka, James Stainer, Lawrence Middleton, Ryan S Dhindsa, Pamela Hill, Ola Engkvist, Andrew R Harper, Slavé Petrovski, Dimitrios Vitsios

Faculty, Staff and Students Publications

No abstract provided.


Mct4-Dependent Lactate Secretion Suppresses Antitumor Immunity In Lkb1-Deficient Lung Adenocarcinoma, Yu Qian, Ana Galan-Cobo, Irene Guijarro, Minghao Dang, David Molkentine, Alissa Poteete, Fahao Zhang, Qi Wang, Jing Wang, Edwin Parra, Apekshya Panda, Jacy Fang, Ferdinandos Skoulidis, Ignacio I Wistuba, Svena Verma, Taha Merghoub, Jedd D Wolchok, Kwok-Kin Wong, Ralph J Deberardinis, John D Minna, Natalie I Vokes, Catherine B Meador, Justin F Gainor, Linghua Wang, Alexandre Reuben, John V Heymach Jul 2023

Mct4-Dependent Lactate Secretion Suppresses Antitumor Immunity In Lkb1-Deficient Lung Adenocarcinoma, Yu Qian, Ana Galan-Cobo, Irene Guijarro, Minghao Dang, David Molkentine, Alissa Poteete, Fahao Zhang, Qi Wang, Jing Wang, Edwin Parra, Apekshya Panda, Jacy Fang, Ferdinandos Skoulidis, Ignacio I Wistuba, Svena Verma, Taha Merghoub, Jedd D Wolchok, Kwok-Kin Wong, Ralph J Deberardinis, John D Minna, Natalie I Vokes, Catherine B Meador, Justin F Gainor, Linghua Wang, Alexandre Reuben, John V Heymach

Faculty, Staff and Student Publications

Inactivating STK11/LKB1 mutations are genomic drivers of primary resistance to immunotherapy in KRAS-mutated lung adenocarcinoma (LUAD), although the underlying mechanisms remain unelucidated. We find that LKB1 loss results in enhanced lactate production and secretion via the MCT4 transporter. Single-cell RNA profiling of murine models indicates that LKB1-deficient tumors have increased M2 macrophage polarization and hypofunctional T cells, effects that could be recapitulated by the addition of exogenous lactate and abrogated by MCT4 knockdown or therapeutic blockade of the lactate receptor GPR81 expressed on immune cells. Furthermore, MCT4 knockout reverses the resistance to PD-1 blockade induced by LKB1 loss in syngeneic …


Potential Biomarker Of Brain Response To Opioid Antagonism In Adolescents With Eating Disorders: A Pilot Study., Stephani L. Stancil, Hung-Wen Yeh, Morgan G. Brucks, Amanda S. Bruce, Michaela Voss, Susan Abdel-Rahman, William M. Brooks, Laura E. Martin Jul 2023

Potential Biomarker Of Brain Response To Opioid Antagonism In Adolescents With Eating Disorders: A Pilot Study., Stephani L. Stancil, Hung-Wen Yeh, Morgan G. Brucks, Amanda S. Bruce, Michaela Voss, Susan Abdel-Rahman, William M. Brooks, Laura E. Martin

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Eating Disorders (ED) affect up to 5% of youth and are associated with reward system alterations and compulsive behaviors. Naltrexone, an opioid antagonist, is used to treat ED behaviors such as binge eating and/or purging. The presumed mechanism of action is blockade of reward activation; however, not all patients respond, and the optimal dose is unknown. Developing a tool to detect objective drug response in the brain will facilitate drug development and therapeutic optimization. This pilot study evaluated neuroimaging as a pharmacodynamic biomarker of opioid antagonism in adolescents with ED.

METHODS: Youth aged 13-21 with binge/purge ED completed functional …


Propensity Score Analysis With Local Balance, Yan Li, Liang Li Jul 2023

Propensity Score Analysis With Local Balance, Yan Li, Liang Li

Faculty, Staff and Student Publications

Most propensity score (PS) analysis methods rely on a correctly specified parametric PS model, which may result in biased estimation of the average treatment effect (ATE) when the model is misspecified. More flexible nonparametric models for treatment assignment alleviate this issue, but they do not always guarantee covariate balance. Methods that force balance in the means of covariates and their transformations between the treatment groups, termed global balance in this article, do not always lead to unbiased estimation of ATE. Their estimated propensity scores only ensure global balance but not the balancing property, which is defined as the conditional independence …


Accumulation Of Chronic Disease Among Survivors Of Childhood Cancer Predicts Early Mortality, Adam J Esbenshade, Lu Lu, Debra L Friedman, Kevin C Oeffinger, Gregory T Armstrong, Kevin R Krull, Joseph P Neglia, Wendy M Leisenring, Rebecca Howell, Robyn Partin, Amy Sketch, Leslie L Robison, Kirsten K Ness Jul 2023

Accumulation Of Chronic Disease Among Survivors Of Childhood Cancer Predicts Early Mortality, Adam J Esbenshade, Lu Lu, Debra L Friedman, Kevin C Oeffinger, Gregory T Armstrong, Kevin R Krull, Joseph P Neglia, Wendy M Leisenring, Rebecca Howell, Robyn Partin, Amy Sketch, Leslie L Robison, Kirsten K Ness

Faculty, Staff and Student Publications

Purpose: Cancer survivors develop cancer and treatment-related morbidities at younger than normal ages and are at risk for early mortality, suggestive of an aging phenotype. The Cumulative Illness Rating Scale for Geriatrics (CIRS-G) is specifically designed to describe the accumulation of comorbidities over time with estimates of severity such as total score (TS) which is a sum of possible conditions weighted by severity. These severity scores can then be used to predict future mortality.

Methods: CIRS-G scores were calculated in cancer survivors and their siblings from Childhood Cancer Survivor Study cohort members from two time points 19 years apart and …


Effect Of Reduced Versus Usual Lipid Emulsion Dosing On Bilirubin Neurotoxicity And Neurodevelopmental Impairment In Extremely Preterm Infants: Study Protocol For A Randomized Controlled Trial, Lindsay F Holzapfel, Cody Arnold, Jon E Tyson, Steven M Shapiro, Eric W Reynolds, Claudia Pedroza, Emily K Stephens, Alan Kleinfeld, Andrew H Huber, Matthew A Rysavy, Maria Del Mar Romero Lopez, Amir M Khan Jul 2023

Effect Of Reduced Versus Usual Lipid Emulsion Dosing On Bilirubin Neurotoxicity And Neurodevelopmental Impairment In Extremely Preterm Infants: Study Protocol For A Randomized Controlled Trial, Lindsay F Holzapfel, Cody Arnold, Jon E Tyson, Steven M Shapiro, Eric W Reynolds, Claudia Pedroza, Emily K Stephens, Alan Kleinfeld, Andrew H Huber, Matthew A Rysavy, Maria Del Mar Romero Lopez, Amir M Khan

Faculty, Staff and Student Publications

BACKGROUND: Bilirubin neurotoxicity (BN) occurs in premature infants at lower total serum bilirubin levels than term infants and causes neurodevelopmental impairment. Usual dose lipid infusions in preterm infants may increase free fatty acids sufficiently to cause bilirubin displacement from albumin, increasing passage of unbound bilirubin (UB) into the brain leading to BN and neurodevelopmental impairment not reliably identifiable in infancy. These risks may be influenced by whether cycled or continuous phototherapy is used to control bilirubin levels.

OBJECTIVE: To assess differences in wave V latency measured by brainstem auditory evoked responses (BAER) at 34-36 weeks gestational age in infants born …


Developing A National-Scale Exposure Index For Combined Environmental Hazards And Social Stressors And Applications To The Environmental Influences On Child Health Outcomes (Echo) Cohort., Sheena E. Martenies, Mingyu Zhang, Anne E. Corrigan, Anton Kvit, Timothy Shields, William Wheaton, Deana Around Him, Judy Aschner, Maria M. Talavera-Barber, Emily S. Barrett, Theresa M. Bastain, Casper Bendixsen, Carrie V. Breton, Nicole R. Bush, Ferdinand Cacho, Carlos A. Camargo, Kecia N. Carroll, Brian S. Carter, Andrea E. Cassidy-Bushrow, Whitney Cowell, Lisa A. Croen, Dana Dabelea, Cristiane S. Duarte, Anne L. Dunlop, Todd M. Everson, Rima Habre, Tina V. Hartert, Jennifer B. Helderman, Alison E. Hipwell, Margaret R. Karagas, Barry M. Lester, Kaja Z. Lewinn, Sheryl Magzamen, Rachel Morello-Frosch, Thomas G. O'Connor, Amy M. Padula, Michael Petriello, Sheela Sathyanarayana, Joseph B. Stanford, Tracey J. Woodruff, Rosalind J. Wright, Amii M. Kress, Program Collaborators For Environmental Influences On Child Health Outcomes Jul 2023

Developing A National-Scale Exposure Index For Combined Environmental Hazards And Social Stressors And Applications To The Environmental Influences On Child Health Outcomes (Echo) Cohort., Sheena E. Martenies, Mingyu Zhang, Anne E. Corrigan, Anton Kvit, Timothy Shields, William Wheaton, Deana Around Him, Judy Aschner, Maria M. Talavera-Barber, Emily S. Barrett, Theresa M. Bastain, Casper Bendixsen, Carrie V. Breton, Nicole R. Bush, Ferdinand Cacho, Carlos A. Camargo, Kecia N. Carroll, Brian S. Carter, Andrea E. Cassidy-Bushrow, Whitney Cowell, Lisa A. Croen, Dana Dabelea, Cristiane S. Duarte, Anne L. Dunlop, Todd M. Everson, Rima Habre, Tina V. Hartert, Jennifer B. Helderman, Alison E. Hipwell, Margaret R. Karagas, Barry M. Lester, Kaja Z. Lewinn, Sheryl Magzamen, Rachel Morello-Frosch, Thomas G. O'Connor, Amy M. Padula, Michael Petriello, Sheela Sathyanarayana, Joseph B. Stanford, Tracey J. Woodruff, Rosalind J. Wright, Amii M. Kress, Program Collaborators For Environmental Influences On Child Health Outcomes

Manuscripts, Articles, Book Chapters and Other Papers

Tools for assessing multiple exposures across several domains (e.g., physical, chemical, and social) are of growing importance in social and environmental epidemiology because of their value in uncovering disparities and their impact on health outcomes. Here we describe work done within the Environmental influences on Child Health Outcomes (ECHO)-wide Cohort Study to build a combined exposure index. Our index considered both environmental hazards and social stressors simultaneously with national coverage for a 10-year period. Our goal was to build this index and demonstrate its utility for assessing differences in exposure for pregnancies enrolled in the ECHO-wide Cohort Study. Our unitless …


Revisional Bariatric Surgery For Weight Recurrence Or Surgical Nonresponse, Erin Briggs, Sunjay Kumar, Francesco Palazzo, Talar Tatarian Jul 2023

Revisional Bariatric Surgery For Weight Recurrence Or Surgical Nonresponse, Erin Briggs, Sunjay Kumar, Francesco Palazzo, Talar Tatarian

Department of Surgery Faculty Papers

No abstract provided.