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Preventative Treatment Of Tuberous Sclerosis Complex With Sirolimus: Phase I Safety And Efficacy Results, Jamie K Capal, David M Ritter, David Neal Franz, Molly Griffith, Kristn Currans, Bridget Kent, E Martina Bebin, Hope Northrup, Mary Kay Koenig, Tomoyuki Mizuno, Alexander A Vinks, Stephanie L Galandi, Wujuan Zhang, Kenneth D R Setchell, Kelly M Kremer, Carlos M Prada, Hansel M Greiner, Katherine Holland-Bouley, Paul S Horn, Darcy A Krueger Jun 2024

Preventative Treatment Of Tuberous Sclerosis Complex With Sirolimus: Phase I Safety And Efficacy Results, Jamie K Capal, David M Ritter, David Neal Franz, Molly Griffith, Kristn Currans, Bridget Kent, E Martina Bebin, Hope Northrup, Mary Kay Koenig, Tomoyuki Mizuno, Alexander A Vinks, Stephanie L Galandi, Wujuan Zhang, Kenneth D R Setchell, Kelly M Kremer, Carlos M Prada, Hansel M Greiner, Katherine Holland-Bouley, Paul S Horn, Darcy A Krueger

Faculty, Staff and Student Publications

Objective: Tuberous sclerosis complex (TSC) results from overactivity of the mechanistic target of rapamycin (mTOR). Sirolimus and everolimus are mTOR inhibitors that treat most facets of TSC but are understudied in infants. We sought to understand the safety and potential efficacy of preventative sirolimus in infants with TSC.

Methods: We conducted a phase 1 clinical trial of sirolimus, treating five patients until 12 months of age. Enrolled infants had to be younger than 6 months of age with no history of seizures and no clinical indication for sirolimus treatment. Adverse events (AEs), tolerability, and blood concentrations of sirolimus measured by …


Endothelial-Specific Telomerase Inactivation Causes Telomere-Independent Cell Senescence And Multi-Organ Dysfunction Characteristic Of Aging, Zhanguo Gao, Rafael Bravo Santos, Joseph Rupert, Rachel Van Drunen, Yongmei Yu, Kristin Eckel-Mahan, Mikhail G Kolonin Jun 2024

Endothelial-Specific Telomerase Inactivation Causes Telomere-Independent Cell Senescence And Multi-Organ Dysfunction Characteristic Of Aging, Zhanguo Gao, Rafael Bravo Santos, Joseph Rupert, Rachel Van Drunen, Yongmei Yu, Kristin Eckel-Mahan, Mikhail G Kolonin

Faculty, Staff and Student Publications

It has remained unclear how aging of endothelial cells (EC) contributes to pathophysiology of individual organs. Cell senescence results in part from inactivation of telomerase (TERT). Here, we analyzed mice with Tert knockout specifically in EC. Tert loss in EC induced transcriptional changes indicative of senescence and tissue hypoxia in EC and in other cells. We demonstrate that EC-Tert-KO mice have leaky blood vessels. The blood-brain barrier of EC-Tert-KO mice is compromised, and their cognitive function is impaired. EC-Tert-KO mice display reduced muscle endurance and decreased expression of enzymes responsible for oxidative metabolism. Our data indicate that Tert-KO EC have …


Insurance Coverage During Transitions: Evidence From Medicaid Automatic Enrollment For Children Receiving Supplemental Security Income, Stephanie Rennane, Danielle Sobol, Bradley D Stein, Andrew Dick Jun 2024

Insurance Coverage During Transitions: Evidence From Medicaid Automatic Enrollment For Children Receiving Supplemental Security Income, Stephanie Rennane, Danielle Sobol, Bradley D Stein, Andrew Dick

Faculty, Staff and Student Publications

OBJECTIVES: To analyze relationships between Medicaid automatic enrollment for child Supplemental Security Income (SSI) recipients and health insurance coverage during transitions.

DATA SOURCES AND STUDY SETTING: Medical Expenditure Panel Study, 2000-2020 and National Survey for Children with Special Health Care Needs, 2001-2010.

STUDY DESIGN: Leveraging variation in SSI-Medicaid automatic enrollment status across regions and over time, we estimate a regression model to quantify associations between automatic enrollment and insurance coverage. We validate our findings in the NS-CSHCN.

DATA COLLECTION: Our sample includes children receiving SSI for a disability. We also analyze a subsample of children newly enrolled in SSI.

PRINCIPAL …


The Unusual Substrate Specificity Of Escherichia Coli Cardiolipin Synthase C Does Not Require The Product Of The Transcriptionally Engaged Ymdb Gene, Katsuhiro Sawasato, Mikhail Bogdanov Jun 2024

The Unusual Substrate Specificity Of Escherichia Coli Cardiolipin Synthase C Does Not Require The Product Of The Transcriptionally Engaged Ymdb Gene, Katsuhiro Sawasato, Mikhail Bogdanov

Faculty, Staff and Student Publications

Polycistronic transcription and translation of ymdB-clsC have been thought to be required for full activity of ClsC. The authentic initiation codon of the clsC gene is present within the open reading frame of the upstream located ymdB gene. ClsC translated from authentic initiation codon drives cardiolipin (CL) synthesis without transcriptionally paired YmdB. YmdB is not necessary for the substrate specificity of ClsC utilizing phosphatidylethanolamine (PE) as a co-substrate.


Management Of Aortoesophageal Fistula Primarily Using Esophageal Preservation, Alexander Mills, Akiko Tanaka, Ashley Dawson, Robert Hetz, Holly Smith, Michael Lopez, Hazim Safi, Anthony Estrera Jun 2024

Management Of Aortoesophageal Fistula Primarily Using Esophageal Preservation, Alexander Mills, Akiko Tanaka, Ashley Dawson, Robert Hetz, Holly Smith, Michael Lopez, Hazim Safi, Anthony Estrera

Faculty, Staff and Student Publications

Objective: Aortoesophageal fistula is a rare, life-threatening condition. There is no consensus regarding the surgical management of the esophagus in this condition.

Methods: We retrospectively evaluated 13 patients diagnosed with aortoesophageal fistulas at a single institution from 2003 to 2021. Descriptive statistics were used to analyze patient characteristics, operative characteristics, and patient outcomes. Kaplan-Meier survival analysis was performed.

Results: Patients' mean age was 63.5 years, and 6 (46.2%) were female. The most common presenting symptoms were hemoptysis/hematemesis (69.2%), chest/back pain (46.2%), and fever (38.5%). Twelve patients (92.3%) had a history of aortic procedures. The median time between the index operation …


The Association Of Nursing Homes' Organizational Context With Care Aide Empowerment: A Cross-Sectional Study, Alba Iaconi, Matthias Hoben, Whitney Berta Phd, Yinfei Duan, Peter G Norton, Yuting Song, Stephanie A Chamberlain, Anna Beeber, Ruth A Anderson, Holly J Lanham, Janelle Perez, Jing Wang, Katharina Choroschun, Shovana Shrestha, Greta Cummings, Carole A Estabrooks Jun 2024

The Association Of Nursing Homes' Organizational Context With Care Aide Empowerment: A Cross-Sectional Study, Alba Iaconi, Matthias Hoben, Whitney Berta Phd, Yinfei Duan, Peter G Norton, Yuting Song, Stephanie A Chamberlain, Anna Beeber, Ruth A Anderson, Holly J Lanham, Janelle Perez, Jing Wang, Katharina Choroschun, Shovana Shrestha, Greta Cummings, Carole A Estabrooks

Faculty, Staff and Student Publications

Background and objectives: Organizational context is thought to influence whether care aides feel empowered, but we lack empirical evidence in the nursing home sector. Our objective was to examine the association of features of nursing homes' unit organizational context with care aides' psychological empowerment.

Research design and methods: This cross-sectional study analyzed survey data from 3765 care aides in 91 Western Canadian nursing homes. Random-intercept mixed-effects regressions were used to examine the associations between nursing home unit organizational context and care aides' psychological empowerment, controlling for care aide, care unit, and nursing home covariates.

Results: Organizational (IVs) culture, social capital, …


Adverse Pregnancy Outcomes And Long-Term Mortality In Women, Casey Crump, Jan Sundquist, Kristina Sundquist Jun 2024

Adverse Pregnancy Outcomes And Long-Term Mortality In Women, Casey Crump, Jan Sundquist, Kristina Sundquist

Faculty, Staff and Student Publications

Importance: Women with adverse pregnancy outcomes, such as preterm delivery or preeclampsia, have higher future risks of cardiometabolic disorders; however, little is known about their long-term mortality risks. A better understanding of such risks is needed to facilitate early identification of high-risk women and preventive actions.

Objective: To determine long-term mortality risks associated with 5 major adverse pregnancy outcomes in a large population-based cohort of women.

Design, setting, and participants: This national cohort study in Sweden used the Swedish Medical Birth Register, containing prenatal and birth information for nearly all deliveries in Sweden since 1973, to identify women who had …


Sociodemographic And Patient Reported Outcomes By Racial And Ethnicity Status Among Participants In A Randomized Controlled Trial For Methamphetamine Use Disorder, Chukwuemeka N Okafor, Thomas Carmody, Angela L Stotts, Gavin Bart, Taryn L Mayes, Tara Karns-Wright, Madhukar Trivedi, Steve Shoptaw, Jennifer S Potter Jun 2024

Sociodemographic And Patient Reported Outcomes By Racial And Ethnicity Status Among Participants In A Randomized Controlled Trial For Methamphetamine Use Disorder, Chukwuemeka N Okafor, Thomas Carmody, Angela L Stotts, Gavin Bart, Taryn L Mayes, Tara Karns-Wright, Madhukar Trivedi, Steve Shoptaw, Jennifer S Potter

Faculty, Staff and Student Publications

Background: There has been a significant increase in methamphetamine use and methamphetamine use disorder (Meth UD) in the United States, with evolving racial and ethnic differences.

Objectives: This secondary analysis explored racial and ethnic differences in baseline sociodemographic and clinical characteristics as well as treatment effects on a measure of substance use recovery, depression symptoms, and methamphetamine craving among participants in a pharmacotherapy trial for Meth UD.

Methods: The ADAPT-2 trial (ClinicalTrials.gov number, NCT03078075; N=403; 69% male) was a multisite, 12-week randomized, double-blind, trial that employed a two-stage sequential parallel design to evaluate the efficacy of combination naltrexone (NTX) …


Unveiling Myeloid Transformation: T-Lgll With Eosinophilia Masking Myeloid-Associated Stat5b Mutation Culminating In Aml, Qianze Dong, Yang Wang, Yan Xiu, Xiaogang Wu, Stacey O'Neill, Howard Meyerson, Tobias Suske, Richard Moriggl, Shimin Hu, Wei Wang, Chen Zhao Jun 2024

Unveiling Myeloid Transformation: T-Lgll With Eosinophilia Masking Myeloid-Associated Stat5b Mutation Culminating In Aml, Qianze Dong, Yang Wang, Yan Xiu, Xiaogang Wu, Stacey O'Neill, Howard Meyerson, Tobias Suske, Richard Moriggl, Shimin Hu, Wei Wang, Chen Zhao

Faculty, Staff and Student Publications

No abstract provided.


Flow Cytometry Profiling Of Plasmacytoid Dendritic Cell Neoplasms, Siba El Hussein, Wei Wang Jun 2024

Flow Cytometry Profiling Of Plasmacytoid Dendritic Cell Neoplasms, Siba El Hussein, Wei Wang

Faculty, Staff and Student Publications

In this review, we aim to provide a summary of the diverse immunophenotypic presentations of distinct entities associated with plasmacytoid dendritic cell (pDC) proliferation. These entities include the following: (1) blastic plasmacytoid dendritic cell neoplasm (BPDCN); (2) mature pDC proliferation (MPDCP), most commonly seen in chronic myelomonocytic leukemia (CMML); and (3) myeloid neoplasms with pDC differentiation, in which pDCs show a spectrum of maturation from early immature pDCs to mature forms, most commonly seen in acute myeloid leukemia (pDC-AML). Our aim is to provide a flow cytometry diagnostic approach to these distinct and sometimes challenging entities and to clarify the …


A Prospective Observational Study Of Disease Severity And Mortality In Hispanic American Patients With Systemic Sclerosis, Bochra Jandali, Marka Lyons, Julio Charles, Meng Zhang, Samuel Theodore, Claudia Pedroza, Maureen D Mayes, Shervin Assassi Jun 2024

A Prospective Observational Study Of Disease Severity And Mortality In Hispanic American Patients With Systemic Sclerosis, Bochra Jandali, Marka Lyons, Julio Charles, Meng Zhang, Samuel Theodore, Claudia Pedroza, Maureen D Mayes, Shervin Assassi

Faculty, Staff and Student Publications

Objective: To characterize disease manifestations in Hispanic American patients with systemic sclerosis (SSc) in comparison with non-Hispanic White and Black patients.

Methods: Longitudinal clinical characteristics were collected prospectively in the Genetics versus Environment in Scleroderma Outcome Study cohort. All patients fulfilled the classification criteria for SSc and had a disease duration less than five years at enrollment.

Results: A cohort of 427 patients, consisting of 124 Hispanic, 220 non-Hispanic White, and 83 non-Hispanic Black participants were examined. At enrollment, Hispanic patients were significantly younger but had longer disease duration, higher frequency of U1-RNP positivity as well as concurrent systemic lupus …


Development Of An Antioxidant-Rich Sugar-Free Plantain Candy And Assessment Of Its Shelf Life In A Flexible Laminate, Poulami Sarkar, Paramita Bhattacharjee, Bidhan Das Jun 2024

Development Of An Antioxidant-Rich Sugar-Free Plantain Candy And Assessment Of Its Shelf Life In A Flexible Laminate, Poulami Sarkar, Paramita Bhattacharjee, Bidhan Das

Faculty, Staff and Student Publications

RESEARCH BACKGROUND: Candy is a popular confection worldwide, and it would be beneficial to society if it were converted into a source of antioxidant molecules to eliminate its adverse health effects. The amount of antioxidants available even in fruit candies is questionable due to the high thermal processing losses they undergo and the presence of various food additives. Plantains (

EXPERIMENTAL APPROACH: To accomplish the first objective, lyophilized plantain powder, sorbitol and mannitol were used as base materials with minimal additives under minimal processing conditions to reduce processing loss. Sensory, proximate, physicochemical and phytochemical properties, including the antioxidant synergy among …


Trends In Shortages Of Lead Chelators From 2001 To 2022, James D Whitledge, Pelayia Soto, Kieran M Glowacki, Diane P Calello, Erin R Fox, Maryann Mazer-Amirshahi Jun 2024

Trends In Shortages Of Lead Chelators From 2001 To 2022, James D Whitledge, Pelayia Soto, Kieran M Glowacki, Diane P Calello, Erin R Fox, Maryann Mazer-Amirshahi

Faculty, Staff and Student Publications

OBJECTIVE: The study aims to describe drug shortages affecting lead chelators in the United States from 2001 through 2022.

METHODS: Drug shortage data were retrieved from the University of Utah Drug Information Service from January 1, 2001, through December 31, 2022. Shortages of first- and second-line lead chelators were analyzed. Drug class, formulation, administration route, shortage reason, shortage duration, generic status, single-source status, and presence of temporally overlapping shortages were examined. Total shortage months, percentages of study period on shortage, and median shortage durations were calculated.

RESULTS: Thirteen lead chelator shortages were reported during the study period. Median duration was …


Response To: Comment On "Effects Of A Pragmatic Home-Based Exercise Program Concurrent With Neoadjuvant Therapy On Physical Function Of Patients With Pancreatic Cancer: The Pancfit Randomized Clinical Trial", An T Ngo-Huang, Nathan H Parker, Keri L Schadler, Matthew H G Katz Jun 2024

Response To: Comment On "Effects Of A Pragmatic Home-Based Exercise Program Concurrent With Neoadjuvant Therapy On Physical Function Of Patients With Pancreatic Cancer: The Pancfit Randomized Clinical Trial", An T Ngo-Huang, Nathan H Parker, Keri L Schadler, Matthew H G Katz

Faculty, Staff and Student Publications

No abstract provided.


Open Tibial Shaft Fracture Fixation Strategies: Intramedullary Nailing, External Fixation, And Plating, Michelle Shen, Nirmal Tejwani Jun 2024

Open Tibial Shaft Fracture Fixation Strategies: Intramedullary Nailing, External Fixation, And Plating, Michelle Shen, Nirmal Tejwani

Faculty, Staff and Student Publications

Tibial shaft fractures are one of the most common orthopaedic injuries. Open tibial shaft fractures are relatively common because of the paucity of soft tissue surrounding the bone. Despite the prevalence of these injuries, the optimal fixation strategy is still a topic of debate. The purpose of this article was to review the current literature on open tibial shaft fracture fixation strategies including intramedullary nailing, external fixation, and plating.


Pharmacokinetic Analysis Of A Phenobarbital Overdose Treated With Urinary Alkalinization Alone, Justin Seltzer, Jeremy Hardin, Henrik Galust, Nathan Friedman, Bryan Corbett, Richard F Clark Jun 2024

Pharmacokinetic Analysis Of A Phenobarbital Overdose Treated With Urinary Alkalinization Alone, Justin Seltzer, Jeremy Hardin, Henrik Galust, Nathan Friedman, Bryan Corbett, Richard F Clark

Faculty, Staff and Student Publications

Phenobarbital is a long-acting barbiturate used to treat alcohol withdrawal and epilepsy. Acute overdoses present with varying levels of central nervous system depression and large overdoses can be life threatening. Phenobarbital is an attractive candidate for enhanced elimination using urinary alkalinization given it is a weak acid with a long half-life and extensive urinary elimination. Limited human data exist regarding use of urine alkalinization for the treatment of phenobarbital overdose. We present a fourteen-year-old female who was treated with urinary alkalinization alone following an intentional ingestion of 3800 mg (84.4 mg/kg) of phenobarbital tablets. Urine drugs of abuse screening was …


Novel Cancer Prevention Strategies In Individuals With Hereditary Cancer Syndromes: Focus On Brca1, Brca2, And Lynch Syndrome, Charles M Bowen, Kaitlin Demarest, Eduardo Vilar, Payal D Shah Jun 2024

Novel Cancer Prevention Strategies In Individuals With Hereditary Cancer Syndromes: Focus On Brca1, Brca2, And Lynch Syndrome, Charles M Bowen, Kaitlin Demarest, Eduardo Vilar, Payal D Shah

Faculty, Staff and Student Publications

Germline pathogenic variants (PVs) in the BRCA1 and BRCA2 genes confer elevated risks of breast, ovarian, and other cancers. Lynch syndrome (LS) is associated with increased risks of multiple cancer types including colorectal and uterine cancers. Current cancer risk mitigation strategies have focused on pharmacologic risk reduction, enhanced surveillance, and preventive surgeries. While these approaches can be effective, they stand to be improved on because of either limited efficacy or undesirable impact on quality of life. The current review summarizes ongoing investigational efforts in cancer risk prevention strategies for patients with germline PVs in BRCA1, BRCA2, or LS-associated …


Understanding Nanoparticle-Liver Interactions In Nanomedicine, Yuxin He, Yifan Wang, Lin Wang, Wen Jiang, Stefan Wilhelm Jun 2024

Understanding Nanoparticle-Liver Interactions In Nanomedicine, Yuxin He, Yifan Wang, Lin Wang, Wen Jiang, Stefan Wilhelm

Faculty, Staff and Student Publications

Introduction: Understanding the interactions between administered nanoparticles and the liver is crucial for developing safe and effective nanomedicines. As the liver can sequester up to 99% of these particles due to its major phagocytic role, understanding these interactions is vital for clinical translation.

Areas covered: This review highlights recent studies on nanoparticle-liver interactions, including the influence of nanoparticle physicochemical properties on delivery, strategies to enhance delivery efficiency by modulating liver Kupffer cells, and their potential for treating certain hepatic diseases. Additionally, we discuss how aging impacts the liver's phagocytic functions.

Expert opinion: While liver accumulation can hinder nanomedicine safety and …


Pegvaliase For The Treatment Of Phenylketonuria: Final Results Of A Long-Term Phase 3 Clinical Trial Program, Cary O Harding, Nicola Longo, Hope Northrup, Stephanie Sacharow, Rani Singh, Janet A Thomas, Jerry Vockley, Roberto T Zori, Kaleigh Bulloch Whitehall, Joshua Lilienstein, Kristin Lindstrom, Drew G Levy, Shaun Jones, Barbara K Burton Jun 2024

Pegvaliase For The Treatment Of Phenylketonuria: Final Results Of A Long-Term Phase 3 Clinical Trial Program, Cary O Harding, Nicola Longo, Hope Northrup, Stephanie Sacharow, Rani Singh, Janet A Thomas, Jerry Vockley, Roberto T Zori, Kaleigh Bulloch Whitehall, Joshua Lilienstein, Kristin Lindstrom, Drew G Levy, Shaun Jones, Barbara K Burton

Faculty, Staff and Student Publications

Phenylketonuria (PKU) is a genetic disorder caused by deficiency of the enzyme phenylalanine hydroxylase (PAH), which results in phenylalanine (Phe) accumulation in the blood and brain, and requires lifelong treatment to keep blood Phe in a safe range. Pegvaliase is an enzyme-substitution therapy approved for individuals with PKU and uncontrolled blood Phe concentrations (>600 μmol/L) despite prior management. Aggregated results from the PRISM clinical trials demonstrated substantial and sustained reductions in blood Phe with a manageable safety profile, but also noted individual variation in time to and dose needed for a first response. This analysis reports longer-term aggregate findings …


Opioid Risk Tool, In-Hospital Opioid Exposure, And Opioid Demand Predict Pain Outcomes Following Traumatic Injury, Danielle A Kessler, Heather E Webber, Constanza De Dios, Jin H Yoon, Joy M Schmitz, Scott D Lane, John A Harvin, Angela M Heads, Charles E Green, Shweta Kapoor, Angela L Stotts, Kandice L Motley, Robert Suchting Jun 2024

Opioid Risk Tool, In-Hospital Opioid Exposure, And Opioid Demand Predict Pain Outcomes Following Traumatic Injury, Danielle A Kessler, Heather E Webber, Constanza De Dios, Jin H Yoon, Joy M Schmitz, Scott D Lane, John A Harvin, Angela M Heads, Charles E Green, Shweta Kapoor, Angela L Stotts, Kandice L Motley, Robert Suchting

Faculty, Staff and Student Publications

Prescribed opioids are a mainstay pain treatment after traumatic injury, but a subgroup of patients may be at risk for continued opioid use. We evaluated the predictive utility of a traditional screening tool, the Opioid Risk Tool (ORT), and two other measures: average in-hospital milligram morphine equivalents (MME) per day and an assessment of opioid demand in predicting pain outcomes. Assessments of pain-related outcomes (pain intensity, interference, injury-related stress, and need for additional pain treatment) were administered at 2 weeks and 12 months post-discharge in a sample of 34 patients hospitalized for traumatic injury. Bayesian linear models were used to …


Current Gaps In Emergency Medicine Core Content Education For Oncologic Emergencies: A Targeted Needs Assessment, Monica K Wattana, Angela Lindsay, Moira Davenport, Nicholas R Pettit, Jazmin R Menendez, Ziyi Li, Demis N Lipe, Aiham Qdaisat, Jason J Bischof Jun 2024

Current Gaps In Emergency Medicine Core Content Education For Oncologic Emergencies: A Targeted Needs Assessment, Monica K Wattana, Angela Lindsay, Moira Davenport, Nicholas R Pettit, Jazmin R Menendez, Ziyi Li, Demis N Lipe, Aiham Qdaisat, Jason J Bischof

Faculty, Staff and Student Publications

Objective: The core content of emergency medicine (EM) residency training includes the management of oncologic emergencies; however, documented knowledge gaps continue to exist in this subtopic. This study represents a targeted needs assessment as indicated by Step 2 of Kern's curriculum design to determine the specific training gaps to be addressed within the oncologic EM curriculum.

Methods: A multi-institutional cross-sectional survey of oncologists (surgical and medical) and emergency physicians (attendings and residents) was conducted during 2023 at five institutions. The voluntary survey consisted of general and specialty-specific questions exploring gaps in oncologic emergency-specific training/education topics. Descriptive statistics reported responses as …


Liver Late Effects In Childhood Cancer Survivors Treated With Radiation Therapy: A Pentec Comprehensive Review, Matthew D Hall, Rebecca M Howell, Andrew Jackson, Constance A Owens, Soleil Hernandez, Sharon M Castellino, Cecile M Ronckers, Louis S Constine, Julie A Bradley Jun 2024

Liver Late Effects In Childhood Cancer Survivors Treated With Radiation Therapy: A Pentec Comprehensive Review, Matthew D Hall, Rebecca M Howell, Andrew Jackson, Constance A Owens, Soleil Hernandez, Sharon M Castellino, Cecile M Ronckers, Louis S Constine, Julie A Bradley

Faculty, Staff and Student Publications

Purpose: A pediatric normal tissue effects in the clinic (PENTEC) comprehensive review of patients with childhood cancer who received radiation therapy (RT) to the liver was performed to develop models that may inform RT dose constraints for the liver and improve risk forecasting of toxicities.

Methods and materials: A systematic literature search was performed to identify published data on hepatic toxicities in children. Treatment and outcome data were extracted and used to generate normal tissue complication probability (NTCP) models. Complications from both whole and partial liver irradiation were considered. For whole liver irradiation, total body irradiation and non-total body irradiation …


Pediatric Normal Tissue Effects In The Clinic (Pentec): An International Collaboration To Assess Normal Tissue Radiation Dose-Volume-Response Relationships For Children With Cancer, Louis S Constine, Arthur J Olch, Andrew Jackson, Chia-Ho Hua, Cecile M Ronckers, Michael T Milano, Karen J Marcus, Ellen Yorke, David C Hodgson, Rebecca M Howell, Melissa M Hudson, Jacqueline P Williams, Brian Marples, Leontien C M Kremer, Lawrence B Marks, Søren M Bentzen Jun 2024

Pediatric Normal Tissue Effects In The Clinic (Pentec): An International Collaboration To Assess Normal Tissue Radiation Dose-Volume-Response Relationships For Children With Cancer, Louis S Constine, Arthur J Olch, Andrew Jackson, Chia-Ho Hua, Cecile M Ronckers, Michael T Milano, Karen J Marcus, Ellen Yorke, David C Hodgson, Rebecca M Howell, Melissa M Hudson, Jacqueline P Williams, Brian Marples, Leontien C M Kremer, Lawrence B Marks, Søren M Bentzen

Faculty, Staff and Student Publications

No abstract provided.


The Impact Of Routine Vaccinations On Alzheimer’S Disease Risk In Persons 65 Years And Older: A Claims-Based Cohort Study Using Propensity Score Matching, Sseu-Pei Hwang, Catherine Denicourt Jun 2024

The Impact Of Routine Vaccinations On Alzheimer’S Disease Risk In Persons 65 Years And Older: A Claims-Based Cohort Study Using Propensity Score Matching, Sseu-Pei Hwang, Catherine Denicourt

Faculty, Staff and Student Publications

The dysregulation of ribosome biogenesis is a hallmark of cancer, facilitating the adaptation to altered translational demands essential for various aspects of tumor progression. This review explores the intricate interplay between ribosome biogenesis and cancer development, highlighting dynamic regulation orchestrated by key oncogenic signaling pathways. Recent studies reveal the multifaceted roles of ribosomes, extending beyond protein factories to include regulatory functions in mRNA translation. Dysregulated ribosome biogenesis not only hampers precise control of global protein production and proliferation but also influences processes such as the maintenance of stem cell-like properties and epithelial-mesenchymal transition, contributing to cancer progression. Interference with ribosome …


Author Correction: Concurrent Intrathecal And Intravenous Nivolumab In Leptomeningeal Disease: Phase 1 Trial Interim Results, Isabella C Glitza Oliva, Sherise D Ferguson, Roland Bassett, Alexandra P Foster, Ida John, Tarin D Hennegan, Michelle Rohlfs, Jessie Richard, Masood Iqbal, Tina Dett, Carol Lacey, Natalie Jackson, Theresa Rodgers, Suzanne Phillips, Sheila Duncan, Lauren Haydu, Ruitao Lin, Rodabe N Amaria, Michael K Wong, Adi Diab, Cassian Yee, Sapna P Patel, Jennifer L Mcquade, Grant M Fischer, Ian E Mccutcheon, Barbara J O'Brien, Sudhakar Tummala, Matthew Debnam, Nandita Guha-Thakurta, Jennifer A Wargo, Fernando C L Carapeto, Courtney W Hudgens, Jason T Huse, Michael T Tetzlaff, Elizabeth M Burton, Hussein A Tawbi, Michael A Davies Jun 2024

Author Correction: Concurrent Intrathecal And Intravenous Nivolumab In Leptomeningeal Disease: Phase 1 Trial Interim Results, Isabella C Glitza Oliva, Sherise D Ferguson, Roland Bassett, Alexandra P Foster, Ida John, Tarin D Hennegan, Michelle Rohlfs, Jessie Richard, Masood Iqbal, Tina Dett, Carol Lacey, Natalie Jackson, Theresa Rodgers, Suzanne Phillips, Sheila Duncan, Lauren Haydu, Ruitao Lin, Rodabe N Amaria, Michael K Wong, Adi Diab, Cassian Yee, Sapna P Patel, Jennifer L Mcquade, Grant M Fischer, Ian E Mccutcheon, Barbara J O'Brien, Sudhakar Tummala, Matthew Debnam, Nandita Guha-Thakurta, Jennifer A Wargo, Fernando C L Carapeto, Courtney W Hudgens, Jason T Huse, Michael T Tetzlaff, Elizabeth M Burton, Hussein A Tawbi, Michael A Davies

Faculty, Staff and Student Publications

No abstract provided.


A Novel Missense Variant Located Within The Zinc Finger Domain Of The Gli3 Gene Was Identified In A Vietnamese Pedigree With Index Finger Polydactyly, Thy Ngoc Nguyen, Giang Son Tran, Hai Duc Hoang, Long Giang Nguyen Jun 2024

A Novel Missense Variant Located Within The Zinc Finger Domain Of The Gli3 Gene Was Identified In A Vietnamese Pedigree With Index Finger Polydactyly, Thy Ngoc Nguyen, Giang Son Tran, Hai Duc Hoang, Long Giang Nguyen

Faculty, Staff and Student Publications

BACKGROUND: Polydactyly, particularly of the index finger, remains an intriguing anomaly for which no specific gene or locus has been definitively linked to this phenotype. In this study, we conducted an investigation of a three-generation family displaying index finger polydactyly.

METHODS: Exome sequencing was conducted on the patient, with a filtration to identify potential causal variation. Validation of the obtained variant was conducted by Sanger sequencing, encompassing all family members.

RESULTS: Exome analysis uncovered a novel heterozygous missense variant (c.1482A>T; p.Gln494His) at the zinc finger DNA-binding domain of the GLI3 protein within the proband and all affected family members. …


Endothelial Knockdown Of The Tumor Suppressor, Wwox, Increases Inflammation In Ventilator-Induced Lung Injury, Zhenguo Zeng, Eltyeb Abdelwahid, Weiguo Chen, Christian Ascoli, Trinh Pham, Jeffrey R Jacobson, Steven M Dudek, Viswanathan Natarajan, C Marcelo Aldaz, Roberto F Machado, Sunit Singla Jun 2024

Endothelial Knockdown Of The Tumor Suppressor, Wwox, Increases Inflammation In Ventilator-Induced Lung Injury, Zhenguo Zeng, Eltyeb Abdelwahid, Weiguo Chen, Christian Ascoli, Trinh Pham, Jeffrey R Jacobson, Steven M Dudek, Viswanathan Natarajan, C Marcelo Aldaz, Roberto F Machado, Sunit Singla

Faculty, Staff and Student Publications

Chronic cigarette smoke exposure decreases lung expression of WWOX which is known to protect the endothelial barrier during infectious models of acute respiratory distress syndrome (ARDS). Proteomic analysis of WWOX-silenced endothelial cells (ECs) was done using tandem mass tag mass spectrometry (TMT-MS). WWOX-silenced ECs as well as those isolated from endothelial cell Wwox knockout (EC Wwox KO) mice were subjected to cyclic stretch (18% elongation, 0.5 Hz, 4 h). Cellular lysates and media supernatant were harvested for assays of cellular signaling, protein expression, and cytokine release. These were repeated with dual silencing of WWOX and zyxin. Control and …


Venetoclax And Cobimetinib In Relapsed/Refractory Aml: A Phase 1b Trial, Marina Y Konopleva, Monique Dail, Naval G Daver, Jacqueline S Garcia, Brian A Jonas, Karen W L Yee, Kevin R Kelly, Norbert Vey, Sarit Assouline, Gail J Roboz, Stefania Paolini, Daniel A Pollyea, Agostino Tafuri, Joseph M Brandwein, Arnaud Pigneux, Bayard L Powell, Pierre Fenaux, Rebecca L Olin, Giuseppe Visani, Giovanni Martinelli, Maika Onishi, Jue Wang, Weize Huang, Diana R Dunshee, Habib Hamidi, Marion G Ott, Wan-Jen Hong, Michael Andreeff Jun 2024

Venetoclax And Cobimetinib In Relapsed/Refractory Aml: A Phase 1b Trial, Marina Y Konopleva, Monique Dail, Naval G Daver, Jacqueline S Garcia, Brian A Jonas, Karen W L Yee, Kevin R Kelly, Norbert Vey, Sarit Assouline, Gail J Roboz, Stefania Paolini, Daniel A Pollyea, Agostino Tafuri, Joseph M Brandwein, Arnaud Pigneux, Bayard L Powell, Pierre Fenaux, Rebecca L Olin, Giuseppe Visani, Giovanni Martinelli, Maika Onishi, Jue Wang, Weize Huang, Diana R Dunshee, Habib Hamidi, Marion G Ott, Wan-Jen Hong, Michael Andreeff

Faculty, Staff and Student Publications

Background: Therapies for relapsed/refractory acute myeloid leukemia remain limited and outcomes poor, especially amongst patients who are ineligible for cytotoxic chemotherapy or targeted therapies.

Patients and methods: This phase 1b trial evaluated venetoclax, a B-cell lymphoma-2 (BCL-2) inhibitor, plus cobimetinib, a MEK1/2 inhibitor, in patients with relapsed/refractory acute myeloid leukemia, ineligible for cytotoxic chemotherapy. Two-dimensional dose-escalation was performed for venetoclax dosed daily, and for cobimetinib dosed on days 1-21 of each 28-day cycle.

Results: Thirty patients (median [range] age: 71.5 years [60-84]) received venetoclax-cobimetinib. The most common adverse events (AEs; in ≥40.0% of patients) were diarrhea (80.0%), nausea (60.0%), vomiting …


Covid-19 Vaccine Confidence, Concerns, And Uptake In Children Aged 5 And Older In Calgary, Alberta: A Longitudinal Cohort Study, Emily J Doucette, Leah Ricketson, Tarannum Tarannum, Isabella Alatorre, Joslyn Gray, Cora Constantinescu, Susan Kuhn, Jessica K E Dunn, James D Kellner Jun 2024

Covid-19 Vaccine Confidence, Concerns, And Uptake In Children Aged 5 And Older In Calgary, Alberta: A Longitudinal Cohort Study, Emily J Doucette, Leah Ricketson, Tarannum Tarannum, Isabella Alatorre, Joslyn Gray, Cora Constantinescu, Susan Kuhn, Jessica K E Dunn, James D Kellner

Faculty, Staff and Student Publications

OBJECTIVES: Beginning early in the pandemic, there was a worldwide effort to develop effective vaccines against the SARS-CoV-2 virus. Before and after the approval and implementation of vaccines, there were concerns about their need as well as their safety and rapid development. We explored child demographic characteristics and parental concerns to identify factors associated with the decision to vaccinate.

METHODS: A cohort of 1035 children from Calgary was assembled in 2020 to participate in 5 visits every 6 months for survey completion and blood sampling for SARS-CoV-2 antibodies. Visits 1 to 2 occurred before approval of vaccines for children; Visits …


Network Meta-Analysis Of Car T-Cell Therapy For The Treatment Of 3l+ R/R Lbcl After Using Published Comparative Studies, Olalekan O Oluwole, Sattva S Neelapu, Markqayne D Ray, Eve H Limbrick-Oldfield, Sally W Wade, Steve Kanters, Anik R Patel, Frederick L Locke Jun 2024

Network Meta-Analysis Of Car T-Cell Therapy For The Treatment Of 3l+ R/R Lbcl After Using Published Comparative Studies, Olalekan O Oluwole, Sattva S Neelapu, Markqayne D Ray, Eve H Limbrick-Oldfield, Sally W Wade, Steve Kanters, Anik R Patel, Frederick L Locke

Faculty, Staff and Student Publications

Introduction: Studies have compared chimeric antigen receptor (CAR) T-cell therapies and salvage chemotherapy in relapsed/refractory large B-cell lymphoma (LBCL) patients, but further evidence of their relative effectiveness is warranted.

Methods: Our systematic review identified studies comparing efficacy and safety outcomes of axicabtagene ciloleucel (axi-cel), lisocabtagene maraleucel (liso-cel) and tisagenlecleucel (tisa-cel) trials to salvage chemotherapy cohorts in LBCL patients with ≥2 prior lines of treatment; and an extended evidence network included indirect comparisons comparing CAR T-cell therapies. We conducted network meta-analyzes using Bayesian hierarchical modeling.

Results: Three studies comparing ZUMA-1 (axi-cel), TRANSCEND (liso-cel) and JULIET (tisa-cel) trials to salvage chemotherapy within …