Medical Specialties Commons^™

A Genomics Driven Induced Pluripotent Stem Cell Model Of Infant Acute Lymphoblastic Leukemia - Early Results, Meagan Vacek, Jacqelyn Nemechek, Irina Pushel, Bradley Thornton, Molly Leyda, Priyanka Prem Kumar, Midhat Farooqi, Jay L. Vivian, Erin M. Guest, John M. Perry

Research Days

While the cure rates for pediatric ALL have improved over the decades, infants with ALL (iALL) have not benefitted from these advances and continue to have a devastating prognosis. Unfortunately progress in treatment has also been slowed by inadequate research models. With this project, we address this unmet need by investigating a novel model to understand the cellular and molecular changes that occur during iALL onset and progression.

Opioid Use After In Situ Fixation Of Slipped Capital Femoral Epiphysis, Stephanie Coupal, Colleen Moreland, Jonathan R. Warren, Mckenna C. Noe, Lisa Berglund, Caleb Grote

Research Days

Preliminary results of a prospective single-institution study evaluating opioid use following in situ screw fixation of Slipped Capital Femoral Epiphysis (SCFE) in pediatric patients.

Characteristics And Clinical Outcomes Of Iud Insertion Under Conscious Sedation In Pediatric And Adolescent Patients, Alleana Corpin, Madeline Ross, Anne-Marie Priebe, Ashli A. Lawson

Research Days

Intrauterine devices (IUDs) are a favorable option for adolescents for contraception and menstrual suppression. However, few choose this option citing anxiety and concern for pain related to insertion procedure. Our institution proposes utilizing conscious sedation techniques for anxiolysis and analgesia during IUD insertion. The objective of this study was to identify characteristics of teens choosing conscious sedation for this procedure and likelihood of successful insertion.

Key Words: Intrauterine device (IUD), adolescent, conscious sedation

Testing For Bleeding Disorders In Child Abuse: Adherence To Aap Recommendations And Results Of Testing., Lyndsey Hultman, James Anderst, Henry T. Puls, Shannon L. Carpenter, Angela Doswell, Angela N. Bachim, Joanne Wood, Kristine Campbell, Daniel M. Lindberg

Research Days

This was a retrospective, descriptive study of bleeding disorder testing practices among subjects in CAPNET, a multicenter research network of children evaluated by Child Abuse Pediatricians for concern of child physical abuse.

Case Of An Adolescent Girl With Familial Vulvar Leiomyoma, Madeline Ross, Charlene Dekonenko, Rebecca Rentea, Tazim Dowlut-Mcelroy

Research Days

Background

While uterine leiomyomas remain a common occurrence affecting nearly 30% of adult women above 35yo, leiomyomas can arise anywhere smooth muscle cells are located in the body. Vulvar leiomyomas are a particularly rare diagnosis, often misdiagnosed as Bartholin gland cyst, comprising 0.07% of vulvar tumors, and thought to arise from smooth muscle within the round ligament, erectile tissue, and dartos muscle. Even more rare is the presentation of vulvar leiomyoma in the adolescent population and family history of vulvar leiomyoma.

Case

We present the case of a 16yo girl who noticed a painless vulvar mass that had increased in …

Increasing Palliative Care Team Involvement In Pediatric Hematopoietic Stem Cell Transplant Patients, Meagan Vacek, Lisa Tarbell, Melissa List, Erin Hall, Jennifer Linebarger, Kelstan Ellis, Gina Jones, Joel Thompson

Research Days

Early implementation of palliative care in pediatric oncology is well established but its role in pediatric hematopoietic stem cell transplant (HSCT) patients is yet to be fully determined. Multiple organizations encourage palliative care involvement in HSCT patients. Our aim was to increase palliative care team consults for patients receiving HSCT for our targeted diagnosis. Though we did not achieve this aim, we were able to increase the palliative care team's involvement in the total cohort of patients undergoing HSCT.

An Increased Failure Rate Of Asparaginase Desensitization With Calaspargase Pegol, Jillian Fry, Erin Guest, Keith August

Research Days

BACKGROUND: Pegaspargase (SS-PEG) became unavailable to younger patients in 2022, leaving calaspargase pegol (SC-PEG) as the only available long-acting asparaginase formulation. SC-PEG has been compared to SS-PEG and found to have similar rates of adverse events and event-free survival. Our institution uses a desensitization protocol for those with asparaginase hypersensitivity reactions. Here we review our experience with desensitization since the transition to SC-PEG. OBJECTIVES: To compare the rate of hypersensitivity reactions, success of desensitization, and need for alternative asparaginase preparations between patients receiving SC-PEG and SS-PEG. METHOD: This is a retrospective, single center study of pediatric patients who received >2 …

Effects Of Drug Delivery On Ppi-Responsive Esophageal Eosinophilia, Alex Biller, Rachel Chevalier, Amornluck Krasaelap, Janelle R. Noel-Macdonnell

Research Days

Determine if formulation of proton pump inhibitory (pill/capsule vs liquid) affects eosinophilic infiltration of esophagus in patients with PPI-Responsive Esophageal Eosinophilia.

Development Of An Endometriosis Toolkit To Support Clinicians In Providing Quality Care For Women, Rachel Hasbun

Doctor of Nursing Practice (DNP) Projects

Abstract

Background: Endometriosis is the abnormal growth of endometrium-like tissue outside the uterine cavity, affecting approximately 11% of women in the United States during their reproductive years. Diagnostic challenges stem from its varied clinical presentations, reliance on laparoscopy for definitive diagnosis, and limited awareness among practitioners and patients, potentially leading to diagnostic delays of up to 13 years.

Problem: The complexities of diagnosing endometriosis in primary care and specialty settings, combined with limited provider awareness and a lack of comprehensive resources, hinder timely and accurate identification. This leads to suboptimal treatment and care for women affected by the condition.

Methods: …

Bilateral Corneal Perforations Due To Elder Neglect, Jaclyn Jordan, Katherine Selman, Richard Byrne

Journal of Geriatric Emergency Medicine

Introduction: Atraumatic corneal melting and perforation is a rare etiology of eye pain and visual loss in the Emergency Department (ED), and xerophthalmia from vitamin A deficiency is primarily described as a cause of blindness in pediatric patients.

Case: A 68-year-old female presented to the ED with worsening eye pain and months of clouding and vision loss. History was limited by cognitive impairment and was provided by spouse. On exam, she was found to have a body mass index of 13.7 kg/m², dry mucous membranes, purulent discharge from both eyes, and opacification and erosion of both corneas. She …

Selective And Brain-Penetrant Acss2 Inhibitors Target Breast Cancer Brain Metastatic Cells, Emily Esquea, Lorela Ciraku, Riley Young, Jessica Merzy, Alexandra Talarico, Nusaiba Ahmed, Mangalam Karuppiah, Anna Ramesh, Adam Chatoff, Claudia Crispim, Adel Rashad, Simon Cocklin, Nathaniel Snyder, Joris Beld, Nicole Simone, Mauricio Reginato, Alexej Dick

Kimmel Cancer Center Faculty Papers

Breast cancer brain metastasis (BCBM) typically results in an end-stage diagnosis and is hindered by a lack of brain-penetrant drugs. Tumors in the brain rely on the conversion of acetate to acetyl-CoA by the enzyme acetyl-CoA synthetase 2 (ACSS2), a key regulator of fatty acid synthesis and protein acetylation. Here, we used a computational pipeline to identify novel brain-penetrant ACSS2 inhibitors combining pharmacophore-based shape screen methodology with absorption, distribution, metabolism, and excretion (ADME) property predictions. We identified compounds AD-5584 and AD-8007 that were validated for specific binding affinity to ACSS2. Treatment of BCBM cells with AD-5584 and AD-8007 leads to …

The Long-Term Effects Of Blood Urea Nitrogen Levels On Cardiovascular Disease And All-Cause Mortality In Diabetes: A Prospective Cohort Study, Hongfang Liu, Xiaoqin Xin, Jinghui Gan, Jungao Huang

Faculty, Staff and Student Publications

BACKGROUND: The long-term effects of blood urea nitrogen(BUN) in patients with diabetes remain unknown. Current studies reporting the target BUN level in patients with diabetes are also limited. Hence, this prospective study aimed to explore the relationship of BUN with all-cause and cardiovascular mortalities in patients with diabetes.

METHODS: In total, 10,507 participants with diabetes from the National Health and Nutrition Examination Survey (1999-2018) were enrolled. The causes and numbers of deaths were determined based on the National Death Index mortality data from the date of NHANES interview until follow-up (December 31, 2019). Multivariate Cox proportional hazard regression models were …

Misstatements, Misperceptions, And Mistakes In Controlling For Covariates In Observational Research, Xiaoxin Yu, Roger S Zoh, David A Fluharty, Luis M Mestre, Danny Valdez, Carmen D Tekwe, Colby J Vorland, Yasaman Jamshidi-Naeini, Sy Han Chiou, Stella T Lartey, David B Allison

Children’s Nutrition Research Center Staff Publications

We discuss 12 misperceptions, misstatements, or mistakes concerning the use of covariates in observational or nonrandomized research. Additionally, we offer advice to help investigators, editors, reviewers, and readers make more informed decisions about conducting and interpreting research where the influence of covariates may be at issue. We primarily address misperceptions in the context of statistical management of the covariates through various forms of modeling, although we also emphasize design and model or variable selection. Other approaches to addressing the effects of covariates, including matching, have logical extensions from what we discuss here but are not dwelled upon heavily. The misperceptions, …

Desvenlafaxine Induced Acute Angle-Closure Glaucoma - Case Report, Venkatesh Babu Dr, Priyankha Kothandaraman Dr, Megha Sadashiv Dr., Kishor M

Digital Journal of Clinical Medicine

The World Health Organization (WHO) estimates that Depressive disorder affects more than 264 million people worldwide. The global prevalence of depression among those who are aged 18 years and older was approximately 4.4%. According to a 2017 study by India's National Institute of Mental Health and Neuroscience s (NIMHANS), 7.5% of the population in the nation suffers from depression affecting one in 20 Indians_[1].

SSRIs ( Selective Serotonin Re uptake Inhibitors) and SNRIs ( serotonin-nor epinephrine re uptake inhibitors) are increasingly the first-line choices of anti-depressant because of their tolerable side-effect profile and low rate of lethality if …

Ael Transformed From Post-Et Myelofibrosis With A Sinusoidal Pattern, Jak2 Mutation, And Biallelic Tp53 Inactivation, Qing Wei, M James You

Faculty, Staff and Student Publications

No abstract provided.

Brg1/Brm Inhibitor Targets Aml Stem Cells And Exerts Superior Preclinical Efficacy Combined With Bet Or Menin Inhibitor, Warren Fiskus, Jessica Piel, Mike Collins, Murphy Hentemann, Branko Cuglievan, Christopher P Mill, Christine E Birdwell, Kaberi Das, John A Davis, Hanxi Hou, Antrix Jain, Anna Malovannaya, Tapan M Kadia, Naval Daver, Koji Sasaki, Koichi Takahashi, Danielle Hammond, Patrick K Reville, Jian Wang, Sanam Loghavi, Rwik Sen, Xinjia Ruan, Xiaoping Su, Lauren B Flores, Courtney D Dinardo, Kapil N Bhalla

Faculty, Staff and Student Publications

BRG1 (SMARCA4) and BRM (SMARCA2) are the mutually exclusive core ATPases of the chromatin remodeling BAF (BRG1/BRM-associated factor) complexes. They enable transcription factors/cofactors to access enhancers/promoter and modulate gene expressions responsible for cell growth and differentiation of acute myeloid leukemia (AML) stem/progenitor cells. In AML with MLL1 rearrangement (MLL1r) or mutant NPM1 (mtNPM1), although menin inhibitor (MI) treatment induces clinical remissions, most patients either fail to respond or relapse, some harboring menin mutations. FHD-286 is an orally bioavailable, selective inhibitor of BRG1/BRM under clinical development in AML. Present studies show that FHD-286 induces differentiation and lethality in AML cells with …

Unraveling Etc Complex I Function In Ferroptosis Reveals A Potential Ferroptosis-Inducing Therapeutic Strategy For Lkb1-Deficient Cancers, Chao Mao, Guang Lei, Amber Horbath, Min Wang, Zhengze Lu, Yuelong Yan, Xiaoguang Liu, Lavanya Kondiparthi, Xiong Chen, Jun Cheng, Qidong Li, Zhihao Xu, Li Zhuang, Bingliang Fang, Joseph R Marszalek, Masha V Poyurovsky, Kellen Olszewski, Boyi Gan

Faculty, Staff and Student Publications

The role of the mitochondrial electron transport chain (ETC) in regulating ferroptosis is not fully elucidated. Here, we reveal that pharmacological inhibition of the ETC complex I reduces ubiquinol levels while decreasing ATP levels and activating AMP-activated protein kinase (AMPK), the two effects known for their roles in promoting and suppressing ferroptosis, respectively. Consequently, the impact of complex I inhibitors on ferroptosis induced by glutathione peroxidase 4 (GPX4) inhibition is limited. The pharmacological inhibition of complex I in LKB1-AMPK-inactivated cells, or genetic ablation of complex I (which does not trigger apparent AMPK activation), abrogates the AMPK-mediated ferroptosis-suppressive effect and sensitizes …

Enhancer Switching In Cell Lineage Priming Is Linked To Erna, Brg1’S At-Hook, And Swi/Snf Recruitment, Dhurjhoti Saha, Srinivas Animireddy, Junwoo Lee, Anna Thommen, Mckenzie M Murvin, Yue Lu, J Mauro Calabrese, Blaine Bartholomew

Faculty, Staff and Student Publications

RNA transcribed from enhancers, i.e., eRNA, has been suggested to directly activate transcription by recruiting transcription factors and co-activators. Although there have been specific examples of eRNA functioning in this way, it is not clear how general this may be. We find that the AT-hook of SWI/SNF preferentially binds RNA and, as part of the esBAF complex, associates with eRNA transcribed from intronic and intergenic regions. Our data suggest that SWI/SNF is globally recruited in cis by eRNA to cell-type-specific enhancers, representative of two distinct stages that mimic early mammalian development, and not at enhancers that are shared between the …

Localization Of Rnas To The Mitochondria-Mechanisms And Functions, Surbhi Sharma, Furqan M Fazal

Faculty, Staff and Students Publications

The mammalian mitochondrial proteome comprises over 1000 proteins, with the majority translated from nuclear-encoded messenger RNAs (mRNAs). Mounting evidence suggests many of these mRNAs are localized to the outer mitochondrial membrane (OMM) in a pre- or cotranslational state. Upon reaching the mitochondrial surface, these mRNAs are locally translated to produce proteins that are cotranslationally imported into mitochondria. Here, we summarize various mechanisms cells use to localize RNAs, including transfer RNAs (tRNAs), to the OMM and recent technological advancements in the field to study these processes. While most early studies in the field were carried out in yeast, recent studies reveal …

Data Mining For Second Malignancies After Car-T, Helen E Heslop

Faculty, Staff and Students Publications

No abstract provided.

Mrd At The End Of Induction And Efs In T-Cell Lymphoblastic Lymphoma: Children’S Oncology Group Trial Aall1231, Robert J Hayashi, Michelle L Hermiston, Brent L Wood, David T Teachey, Meenakshi Devidas, Zhiguo Chen, Robert D Annett, Barbara L Asselin, Keith August, Steve Cho, Kimberly P Dunsmore, Jason Lawrence Freedman, Paul J Galardy, Paul Harker-Murray, Terzah M Horton, Alok Jaju, Allison Lam, Yoav H Messinger, Rodney R Miles, Maki Okada, Samir Patel, Eric S Schafer, Tal Schechter, Kristin A Shimano, Neelam Singh, Amii Steele, Maria L Sulis, Sarah L Vargas, Stuart S Winter, Charlotte Wood, Patrick A Zweidler-Mckay, Mignon L Loh, Stephen P Hunger, Elizabeth A Raetz, Catherine M Bollard, Carl E Allen

Faculty, Staff and Students Publications

Defining prognostic variables in T-lymphoblastic lymphoma (T-LL) remains a challenge. AALL1231 was a Children’s Oncology Group phase 3 clinical trial for newly diagnosed patients with T acute lymphoblastic leukemia or T-LL, randomizing children and young adults to a modified augmented Berlin-Frankfurt-Münster backbone to receive standard therapy (arm A) or with addition of bortezomib (arm B). Optional bone marrow samples to assess minimal residual disease (MRD) at the end of induction (EOI) were collected in T-LL analyzed to assess the correlation of MRD at the EOI to event-free survival (EFS). Eighty-six (41%) of the 209 patients with T-LL accrued to this …

Variation In Systemic Corticosteroid Prescribing During Asthma-Related Hospitalizations Across Children's Hospitals, Sian Best, Kathryn Kyler, Matt Hall, Jessica L. Bettenhausen, Shelby Chesbro, Nicholas Clark, Adrienne Deporre, Jonathan Ermer, Leah Jones, Jessica Markham, Maria Newmaster, Laura Plencner, Henry T. Puls, Smit Shah, Bridgette Jones, Megan Collins, Elisha Mccoy

Research Days

This abstract describes the variability and trends in inpatient systemic corticosteroid prescribing practices for acute asthma exacerbations in children's hospitals, and aims to determine associations between the prescribed steroid and hospitalization outcomes.

Bowel Clean Out Prior To Intrathecal Baclofen Pump Implantation: Effects On Acute Post-Operative Gastrointestinal Complications, Amanda Lindenberg, Sathya Vadivelu, Brittni Walton, Matthew J. Mclaughlin

Research Days

Background: Intrathecal baclofen (ITB) pumps have been used for management of spasticity and dystonia There is limited data on immediate post-operative complications such as GI adverse events after surgery for ITB pump related procedures. This study aimed to compare patients who underwent a pre-operative bowel cleanout to those who did not and the relationship with post-operative nausea, vomiting and constipation requiring an escalation of their bowel regimen.

Design: Retrospective cohort study.

Setting: Pediatric acute care hospital.

Participants: All patients who underwent new ITB pump and/or catheter placement from January 2015-December 2022.

Interventions: Preoperative bowel clean out. Main

Outcome Measure: Quantity …

Therapeutic Efficacy Of B7-H3 Car T Cell Therapy In Pediatric High-Grade Gliomas With H3g34r/V Mutation., Monika Yadav, Siddharth Subham, John Szarejko, Douglas Myers, David Akhavan, Viveka Nand Yadav

Research Days

Background: Pediatric high-grade gliomas (pHGGs) are aggressive brain tumors responsible for significant childhood mortality. These tumors often carry mutations in the H3F3A gene, which encodes histone H3.3 proteins. However, current treatment options are limited, underscoring the need for innovative approaches. Chimeric antigen receptor (CAR) therapy, which was successful in treating certain childhood cancers, holds promise for pHGGs with H3G34R/V mutations. This study aims to assess the potential of anti-B7-H3 CAR T cell therapy in treating the challenging pHGG tumors.

Method and Results: Here, we examined the expression of B7-H3 in various pHGG cell lines, encompassing those with H3G34V/R and H3K27M …

Characterizing New Invasive Infections In Children’S Mercy Extracorporeal Membrane Oxygenation And And Continuous Renal Replacement Therapy Patients, Samantha M. Davidson, Jay F. Rilinger, Jenna O. Miller, Caroline Holten, Josh Herigon

Research Days

This abstract characterizes the patients at Children's Mercy who developed a new serious bacterial infection while on extracorporeal support.

Central Venous Catheter-Associated Complications In Pediatric Patients With Acute Myeloid Leukemia, J Allyson Hays, Maggie Ziegler

Research Days

Background

Central venous catheters (CVCs) are a mainstay of pediatric cancer treatment for but have risks. CVCs can cause local site infections and systemic infections, known as central-line-associated bloodstream infections (CLABSIs). Analyzing rates of complications associated with different CVCs may inform future decisions about CVC choice. Hypotheses We hypothesized that tunneled cuffed (tunneled) catheters will have higher rates of CLABSIs compared to implanted ports (port) and ports will have higher rates of local site infections compared to tunneled.

Methods

Retrospective chart review of patients with acute myeloid leukemia (AML) at Children’s Mercy Hospital (CMH) identified patients treated from 2010 to …

Pediatric Caregiver Perspectives On Immigration Status In The Healthcare Setting, Anik Patel, Kimberly Randell, Jennifer Watts, John Cowden, Frances Turcotte Benedict, Juan Farias Torres, Ana Contreras, Ali Fowler, Estefania Bazan, Claudia Zepeda

Research Days

A qualitative study to explore pediatric parent/caregiver knowledge, attitudes, and beliefs regarding impacts of immigrant status on healthcare and describe health and social needs of families for whom one or more caregivers has undocumented immigration status as well as preferred methods for resource connections among undocumented caregivers.

Frailty In Children And Adolescents With Acute Lymphoblastic Leukemia Or Lymphoblastic Lymphoma Receiving Maintenance Chemotherapy – A Pilot Study, Thomas R. Cochran, Joy M. Fulbright, Samantha Butrous, Brian R. Lee, Keith J. August, David A. White

Research Days

The submitted study aims to identify children with acute lymphoblastic leukemia or lymphoblastic lymphoma that meet frailty criteria early to allow for prevention of chronic health conditions that lead to increased mortality as survivors age into adulthood. Prevention and/or reversal of frailty has the potential to improve quality of life, decrease burden of disease, and extend the lifespan of the growing population of childhood cancer survivors. Given that frailty has been accepted as a tool to identify elderly and chronically sick adults highly vulnerable to adverse health outcomes, better understanding of the relevance and applicability of frailty in pediatrics may …

Increasing Feedback From Endocrinology Faculty To Fellows: A Quality Improvement Initiative, Emily Metzinger, Emily Griffing, Michelle Knoll

Research Days

Feedback is essential in medical training. Our aim is to increase the frequency of feedback that CMH endocrinology fellows receive in both the inpatient and outpatient settings. We noted initial success of increasing feedback in the inpatient setting however later decreased to below goal. Frequency of feedback in the outpatient setting has remained below goal. Tracking feedback has been challenging, but a recent survey showed that fellows perceive that they receive more feedback.

Let's Talk About Sex & Prep: District 2 Does!, Chrissa M. Shaffer

Georgia Public Health Association Annual Meeting & Conference

Defining what a PrEP Service Program entails and how it could benefit your district or county health center. Discussing methods that have been used to set up PrEP Services within a district – including training, resources, and promotion. Identifying the challenges and working through them. Reviewing the results of the PrEP Services over the past year, and the ongoing goals to encourage and increase our PrEP Services.