Digital Commons Network^™

Use, Durability, And Risks For Discontinuation Of Initial And Subsequent Biologics In A Large Pediatric-Onset Ibd Cohort., Jess L. Kaplan, Chunyan Liu, Eileen C. King, Julie A. Bass, Ashish S. Patel, Jeanne Tung, Shiran Chen, Trevor Lissoos, Ninfa Candela, Shehzad Saeed, Richard B. Colletti, Improvecarenow Network

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Biologic medications are recommended for treatment of moderately-to-severely active Crohn disease (CD) or ulcerative colitis (UC) in children. However, many patients require sequential biologic treatment because of nonresponse or loss of response to the initial biologic.

METHODS: We analyzed pediatric inflammatory bowel disease (IBD) data from the ImproveCareNow Network registry between May 2006 and September 2016, including time to biologic initiation, choice of first subsequent biologics, biologic durability, and reasons for discontinuation.

RESULTS: Of 17,649 patients with IBD [CD: 12,410 (70%); UC: 5239 (30%)], 7585 (43%) were treated with a biologic agent before age 18 (CD: 50%; UC: 25%). …

A Parathyroid Hormone/Salt-Inducible Kinase Signaling Axis Controls Renal Vitamin D Activation And Organismal Calcium Homeostasis, Sung-Hee Yoon, Mark B Meyer, Carlos Arevalo, Murat Tekguc, Chengcheng Zhang, Jialiang S Wang, Christian D Castro Andrade, Katelyn Strauss, Tadatoshi Sato, Nancy A Benkusky, Seong Min Lee, Rebecca Berdeaux, Marc Foretz, Thomas B Sundberg, Ramnik J Xavier, Charles H Adelmann, Daniel J Brooks, Anthony Anselmo, Ruslan I Sadreyev, Ivy A Rosales, David E Fisher, Navin Gupta, Ryuji Morizane, Anna Greka, J Wesley Pike, Michael Mannstadt, Marc N Wein

Faculty, Staff and Student Publications

The renal actions of parathyroid hormone (PTH) promote 1,25-vitamin D generation; however, the signaling mechanisms that control PTH-dependent vitamin D activation remain unknown. Here, we demonstrated that salt-inducible kinases (SIKs) orchestrated renal 1,25-vitamin D production downstream of PTH signaling. PTH inhibited SIK cellular activity by cAMP-dependent PKA phosphorylation. Whole-tissue and single-cell transcriptomics demonstrated that both PTH and pharmacologic SIK inhibitors regulated a vitamin D gene module in the proximal tubule. SIK inhibitors increased 1,25-vitamin D production and renal Cyp27b1 mRNA expression in mice and in human embryonic stem cell–derived kidney organoids. Global- and kidney-specific Sik2/Sik3 mutant mice showed Cyp27b1 upregulation, …

Food Insecurity, Snap Participation And Glycemic Control In Low-Income Adults With Predominantly Type 2 Diabetes: A Cross-Sectional Analysis Using Nhanes 2007-2018 Data, Oluwatobi Alawode, Sarah Humble, Cynthia J Herrick

2020-Current year OA Pubs

INTRODUCTION: Diabetes, characterized by elevated blood glucose levels, affects 13% of US adults, 95% of whom have type 2 diabetes (T2D). Social determinants of health (SDoH), such as food insecurity, are integral to glycemic control. The Supplemental Nutrition Assistance Program (SNAP) aims to reduce food insecurity, but it is not clear how this affects glycemic control in T2D. This study investigated the associations between food insecurity and other SDoH and glycemic control and the role of SNAP participation in a national socioeconomically disadvantaged sample.

RESEARCH DESIGN AND METHODS: Adults with likely T2D and income

RESULTS: The study population included 2084 …

Effectiveness Of Lactation Cookies On Human Milk Production Rates: A Randomized Controlled Trial, Ana M Palacios, Michelle I Cardel, Erik Parker, Stephanie Dickinson, Valerie R Houin, Bridget Young, David B Allison

Children’s Nutrition Research Center Staff Publications

Background: Expensive lactation cookies (LCs) are marketed as milk boosters; however, their effectiveness remains unknown.

Objectives: The objective of this study was to evaluate the effectiveness of the 1-mo daily intake of LCs on changes in objective and subjective milk production and breastfeeding self-efficacy.

Methods: This is a 1-mo, randomized controlled trial among 18-45-y-old exclusively lactating parents of healthy, term, 2-mo-old infants living in the United States from March to December 2021. Participants (n = 176) were randomly assigned to eat daily 56.5 g of either LCs with "galactagogues" (oatmeal, brewer's yeast, flax seeds, and fenugreek) or conventional cookies containing …

Reliability Estimates For Assessing Meal Timing Derived From Longitudinal Repeated 24-Hour Dietary Recalls, Lacie Peterson, Hyejung Lee, Inge Huybrechts, Carine Biessy, Marian L Neuhouser, Benjamin Haaland, Benjamin Krick, Marc Gunter, Matthias B Schulze, Franziska Jannasch, Adriana M Coletta, Sheetal Hardikar, Amandine Chaix, Cici X Bauer, Qian Xiao, Mary C Playdon

Faculty, Staff and Student Publications

BACKGROUND: Regulating meal timing may have efficacy for improving metabolic health for preventing or managing chronic disease. However, the reliability of measuring meal timing with commonly used dietary assessment tools needs characterization prior to investigating meal timing and health outcomes in epidemiologic studies.

OBJECTIVES: to evaluate the reliability of estimating meal timing parameters, including overnight fasting duration, the midpoint of overnight fasting time, the number of daily eating episodes, the period with the largest percentage of daily caloric intake, and late last eating episode (> 09:00 pm) from repeated 24-h dietary recalls (24HRs).

METHODS: Intraclass correlation coefficients (ICC), Light's Kappa …

The Wnt/Pcp Formin Daam1 Drives Cell-Cell Adhesion During Nephron Development, Heather S Carr, Yan Zuo, Jeffrey A Frost

Faculty, Staff and Student Publications

The Somatostatin receptor 2 (Sstr2) is a heterotrimeric G protein-coupled receptor that is highly expressed in neuroendocrine tumors and is a common pharmacological target for intervention. Unfortunately, not all neuroendocrine tumors express Sstr2, and Sstr2 expression can be downregulated with prolonged agonist use. Sstr2 is rapidly internalized following agonist stimulation and, in the short term, is quantitatively recycled back to the plasma membrane. However, mechanisms controlling steady state expression of Sstr2 in the absence of agonist are less well described. Here, we show that Sstr2 interacts with the Wnt pathway protein Dvl1 in a ligand-independent manner to target Sstr2 for …

Dna Methylation Analysis Is Used To Identify Novel Genetic Loci Associated With Circulating Fibrinogen Levels In Blood, Julie Hahn, Jan Bressler, Arce Domingo-Relloso, Ming-Huei Chen, Daniel L Mccartney, Alexander Teumer, Jenny Van Dongen, Marcus E Kleber, Dylan Aïssi, Brenton R Swenson, Jie Yao, Wei Zhao, Jian Huang, Yujing Xia, Michael R Brown, Ricardo Costeira, Eco J C De Geus, Graciela E Delgado, Dre'von A Dobson, Paul Elliott, Hans J Grabe, Xiuqing Guo, Sarah E Harris, Jennifer E Huffman, Sharon L R Kardia, Yongmei Liu, Stefan Lorkowski, Riccardo E Marioni, Matthias Nauck, Scott M Ratliff, Maria Sabater-Lleal, Tim D Spector, Pierre Suchon, Kent D Taylor, Florian Thibord, David-Alexandre Trégouët, Kerri L Wiggins, Gonneke Willemsen, Jordana T Bell, Dorret I Boomsma, Shelley A Cole, Simon R Cox, Abbas Dehghan, Andreas Greinacher, Karin Haack, Winfried März, Pierre-Emmanuel Morange, Jerome I Rotter, Nona Sotoodehnia, Maria Tellez-Plaza, Ana Navas-Acien, Jennifer A Smith, Andrew D Johnson, Myriam Fornage, Nicholas L Smith, Alisa S Wolberg, Alanna C Morrison, Paul S De Vries

Faculty, Staff and Student Publications

Background:

Fibrinogen plays an essential role in blood coagulation and inflammation. Circulating fibrinogen levels may be determined by inter-individual differences in DNA methylation at CpG sites, and vice versa.

Methods:

We performed an epigenome-wide association study (EWAS) of circulating fibrinogen levels in 18,037 White, Black, American Indian, and Hispanic participants representing 14 studies from the CHARGE consortium. Circulating leukocyte DNA methylation was measured in 12,904 participants using the Illumina 450K array, and in 5,133 participants using the EPIC array. Each study performed an EWAS of fibrinogen using linear mixed models adjusted for potential confounders. Study-specific results were combined using array-specific …

Rationale And Design Of Integrating A Parents First Obesity Intervention With A Pediatric Weight Management Intervention For Rural Families - Evaluating The Ripple Effect., Ann M. Davis, Christie A. Befort, Brittany D. Lancaster, Chris Tuck, Barbara J. Polivka, Jordan A. Carlson, Kandace Fleming, Rebecca Swinburne Romine, Kelsey Dean, Megan Murray

Manuscripts, Articles, Book Chapters and Other Papers

Rural families are disproportionately affected by obesity. Obesity often runs in families and is impacted by hereditary components, the shared home environment, and parent modeling/child observational learning. Moreover, parent changes in weight predict child changes in weight. Thus, targeting the family unit has the potential to enhance outcomes for adults and children simultaneously. Additionally, engaging rural nurses in medical clinics and schools may be important in determining whether rural telehealth programs are successfully implemented and sustained. This paper describes the rationale and design of a randomized control trial (RCT) evaluating the effectiveness of an integrated adult- and child-focused obesity treatment …

Impact Of Biomarker-Matched Therapies On Outcomes In Patients With Sarcoma Enrolled In Early-Phase Clinical Trials (Samba 101), Roberto Carmagnani Pestana, Justin T Moyers, Jason Roszik, Shiraj Sen, David S Hong, Aung Naing, Cynthia E Herzog, Siqing Fu, Sarina A Piha-Paul, Jordi Rodon, Timothy A Yap, Daniel D Karp, Apostolia M Tsimberidou, Shubham Pant, Maria A Zarzour, Ravin Ratan, Vinod Ravi, Robert S Benjamin, Alexander J Lazar, Wei-Lien Wang, Najat Daw, Jonathan B Gill, Douglas J Harrison, Valerae O Lewis, Christina L Roland, Shreyaskumar R Patel, J Andrew Livingston, Neeta Somaiah, Joseph A Ludwig, Anthony P Conley, Nelson Hamerschlak, Richard Gorlick, Funda Meric-Bernstam, Vivek Subbiah

Faculty, Staff and Student Publications

Purpose: Developing new therapeutics for any of the more than 100 sarcoma subtypes presents a challenge. After progression from standard therapies, patients with sarcoma may be referred for enrollment in early-phase trials. This study aimed to investigate whether enrollment in biomarker-matched early-phase clinical trials leads to better outcomes for patients with advanced sarcoma.

Experimental design: In this retrospective analysis, investigational treatment characteristics and longitudinal survival outcomes were analyzed in patients with biopsy-confirmed sarcoma enrolled in early-phase trials at MD Anderson Cancer Center from May 2006 to July 2021.

Results: Five hundred eighty-seven patients were included [405 soft tissue, 122 bone, …

Does The Type Of Chronic Heart Failure Impact In-Hospital Outcomes For Aortic Valve Replacement Procedures?, Talha Mubashir, John Zaki, Sin Yeong An, Ismael A Salas De Armas, Yafen Liang, Travis Markham, Han Feng, Mehmet H Akay, Angelo Nascimbene, Bindu Akkanti, George W Williams, Fabricio Zasso, Maria Patarroyo Aponte, Igor D Gregoric, Biswajit Kar

Faculty, Staff and Student Publications

BACKGROUND: This study assessed in-hospital outcomes of patients with chronic systolic, diastolic, or mixed heart failure (HF) undergoing transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR).

METHODS: The Nationwide Inpatient Sample database was used to identify patients with aortic stenosis and chronic HF who underwent TAVR or SAVR between 2012 and 2015. Propensity score matching and multivariate logistic regression were used to determine outcome risk.

RESULTS: A cohort of 9,879 patients with systolic (27.2%), diastolic (52.2%), and mixed (20.6%) chronic HF were included. No statistically significant differences in hospital mortality were noted. Overall, patients with diastolic HF …

Clinical Consensus Guideline On The Management Of Phaeochromocytoma And Paraganglioma In Patients Harbouring Germline Sdhd Pathogenic Variants, David Taïeb, George B Wanna, Maleeha Ahmad, Charlotte Lussey-Lepoutre, Nancy D Perrier, Svenja Nölting, Laurence Amar, Henri J L M Timmers, Zachary G Schwam, Anthony L Estrera, Michael Lim, Erqi Liu Pollom, Lucas Vitzthum, Isabelle Bourdeau, Ruth T Casey, Frédéric Castinetti, Roderick Clifton-Bligh, Eleonora P M Corssmit, Ronald R De Krijger, Jaydira Del Rivero, Graeme Eisenhofer, Hans K Ghayee, Anne-Paule Gimenez-Roqueplo, Ashley Grossman, Alessio Imperiale, Jeroen C Jansen, Abhishek Jha, Michiel N Kerstens, Henricus P M Kunst, James K Liu, Eamonn R Maher, Daniele Marchioni, Leilani B Mercado-Asis, Ozgur Mete, Mitsuhide Naruse, Naris Nilubol, Neeta Pandit-Taskar, Frédéric Sebag, Akiyo Tanabe, Jiri Widimsky, Leah Meuter, Jacques W M Lenders, Karel Pacak

Faculty, Staff and Student Publications

Patients with germline SDHD pathogenic variants (encoding succinate dehydrogenase subunit D; ie, paraganglioma 1 syndrome) are predominantly affected by head and neck paragangliomas, which, in almost 20% of patients, might coexist with paragangliomas arising from other locations (eg, adrenal medulla, para-aortic, cardiac or thoracic, and pelvic). Given the higher risk of tumour multifocality and bilaterality for phaeochromocytomas and paragangliomas (PPGLs) because of SDHD pathogenic variants than for their sporadic and other genotypic counterparts, the management of patients with SDHD PPGLs is clinically complex in terms of imaging, treatment, and management options. Furthermore, locally aggressive disease can be discovered at a …

Epidemiology Of Retinopathy Of Prematurity In The Us From 2003 To 2019, Anshul Bhatnagar, Henry C Skrehot, Amit Bhatt, Honey Herce, Christina Y Weng

Faculty, Staff and Students Publications

IMPORTANCE: Retinopathy of prematurity (ROP) is a potentially blinding retinal disease with poorly defined epidemiology. Understanding of which infants are most at risk for developing ROP may foster targeted detection and prevention efforts.

OBJECTIVE: To identify changes in ROP incidence in the US from 2003 to 2019.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective database cohort study used the Healthcare Cost and Utilization Project Kids' Inpatient Databases. These nationwide databases are produced every 3 years, include data from over 4000 hospitals, and are designed to generate national estimates of health care trends in the US. Participants included pediatric newborns at risk …

Elevated Bile Acids Are Associated With Left Ventricular Structural Changes In Biliary Atresia, Manpreet K Virk, Muhammad Umair M Mian, Dalia A Bashir, John K Wilkes, Tobias Schlingman, Saul Flores, Curtis Kennedy, Fong Lam, Ayse A Arikan, Trung Nguyen, Krupa Mysore, Nhu Thao Nguyen Galvan, Jorge Coss-Bu, Saul J Karpen, Sanjiv Harpavat, Moreshwar S Desai

Faculty, Staff and Students Publications

BACKGROUND: In children with biliary atresia (BA), pathologic structural changes within the heart, which define cirrhotic cardiomyopathy, are associated with adverse perioperative outcomes. Despite their clinical relevance, little is known about the pathogenesis and triggers of pathologic remodeling. Bile acid excess causes cardiomyopathy in experimental cirrhosis, but its role in BA is poorly understood.

METHODS: Echocardiographic parameters of left ventricular (LV) geometry [LV mass (LVM), LVM indexed to height, left atrial volume indexed to BSA (LAVI), and LV internal diameter (LVID)] were correlated with circulating serum bile acid concentrations in 40 children (52% female) with BA listed for transplantation. A …

Cognitive Function Following Diabetic Ketoacidosis In Young Children With Type 1 Diabetes, Simona Ghetti, Nathan Kuppermann, Arleta Rewers, Sage R Myers, Jeff E Schunk, Michael J Stoner, Aris Garro, Kimberly S Quayle, Kathleen M Brown, Jennifer L Trainor, Leah Tzimenatos, Andrew D Depiero, Julie K Mcmanemy, Lise E Nigrovic, Maria Y Kwok, Cody S Olsen, T Charles Casper, Nicole S Glaser, Pediatric Emergency Care Applied Research Network (Pecarn) Dka Fluid Study Group

Faculty, Staff and Students Publications

INTRODUCTION: Young children with type 1 diabetes (T1D) may be at particularly high risk of cognitive decline following diabetic ketoacidosis (DKA). However, studies of cognitive functioning in T1D typically examine school-age children. The goal of this study was to examine whether a single experience of DKA is associated with lower cognitive functioning in young children. We found that recently diagnosed 3- to 5-year-olds who experienced one DKA episode, regardless of its severity, exhibited lower IQ scores than those with no DKA exposure.

METHODS: We prospectively enrolled 46 3- to 5-year-old children, who presented with DKA at the onset of T1D, …

Surgical Reconstruction Of Stage 3 And 4 Pressure Injuries: A Literature Review And Proposed Algorithm From An Interprofessional Working Group, Samir S Awad, James D Stern, Cathy T Milne, Shane G Dowling, Ron Sotomayor, Elizabeth A Ayello, Leandro J Feo Aguirre, Basil Z Khalaf, Lisa J Gould, Michael N Desvigne, Abigail E Chaffin

Faculty, Staff and Students Publications

OBJECTIVE: Stage 3 and 4 pressure injuries (PIs) present an enormous societal burden with no clearly defined interventions for surgical reconstruction. The authors sought to assess, via literature review and a reflection/evaluation of their own clinical practice experience (where applicable), the current limitations to the surgical intervention of stage 3 or 4 PIs and propose an algorithm for surgical reconstruction.

METHODS: An interprofessional working group convened to review and assess the scientific literature and propose an algorithm for clinical practice. Data compiled from the literature and a comparison of institutional management were used to develop an algorithm for the surgical …

Perception And Awareness Of Diabetes Risk And Reported Risk-Reducing Behaviors In Adolescents, Patricia Chu, Arya Patel, Vicki Helgeson, Andrea B Goldschmidt, Mary Katherine Ray, Mary Ellen Vajravelu

2020-Current year OA Pubs

IMPORTANCE: Lifestyle change is central to diabetes risk reduction in youth with overweight or obesity. Feeling susceptible to a health threat can be motivational in adults.

OBJECTIVE: To evaluate associations between diabetes risk perception and/or awareness and health behaviors in youth.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed data from the US National Health and Nutrition Examination Survey 2011 to 2018. Participants included youths aged 12 to 17 years with body mass index (BMI) in the 85th percentile or higher without known diabetes. Analyses were conducted from February 2022 to February 2023.

MAIN OUTCOMES AND MEASURES: Outcomes included physical …

Patterns In Use And Transplant Outcomes Among Adult Recipients Of Kidneys From Deceased Donors With Covid-19, Mengmeng Ji, Amanda J Vinson, Su-Hsin Chang, Massini Merzkani, Krista L Lentine, Yasar Caliskan, Kristin Progar, Nicole Nesselhauf, Casey Dubrawka, Tarek Alhamad

2020-Current year OA Pubs

IMPORTANCE: While the COVID-19 pandemic enters a new phase and the proportion of individuals with a previous COVID-19 diagnosis increases, the national patterns in kidney use and medium-term kidney transplant (KT) outcomes among patients receiving kidneys from active or resolved COVID-19-positive donors remain unknown.

OBJECTIVE: To evaluate the patterns in kidney use and KT outcomes among adult recipients of kidneys from deceased donors with active or resolved COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted using national US transplant registry data from 35 851 deceased donors (71 334 kidneys) and 45 912 adult patients who received KTs …

Adapting Elements Of Cleft Care Protocols In Low- And Middle-Income Countries During And After Covid-19: A Process-Driven Review With Recommendations, Matthew Fell, Michael Goldwasser, B S Jayanth, Rui Manuel Rodrigues Pereira, Christian Tshisuz Nawej, Rachel Winer, Neeti Daftari, Hugh Brewster, Karen Goldschmied, Collaborators Fernando Almas, Mekonen Eshete, George W Galiwango, Larry H Hollier, Akhter Hussain, Lun-Jou Lo, Paul Salins, Debbie Sell, Amanuel Tafase, Ronald M Zuker

Faculty, Staff and Students Publications

A consortium of global cleft professionals, predominantly from low- and middle-income countries, identified adaptations to cleft care protocols during and after COVID-19 as a priority learning area of need. A multidisciplinary international working group met on a videoconferencing platform in a multi-staged process to make consensus recommendations for adaptations to cleft protocols within resource-constrained settings. Feedback was sought from a roundtable discussion forum and global organizations involved in comprehensive cleft care. Foundational principles were agreed to enable recommendations to be globally relevant and two areas of focus within the specified topic were identified. First the safety aspects of cleft surgery …

Investigating Gene-Diet Interactions Impacting The Association Between Macronutrient Intake And Glycemic Traits, Kenneth E Westerman, Maura E Walker, Sheila M Gaynor, Jennifer Wessel, Daniel Dicorpo, Jiantao Ma, Alvaro Alonso, Stella Aslibekyan, Abigail S Baldridge, Alain G Bertoni, Mary L Biggs, Jennifer A Brody, Yii-Der Ida Chen, Joseé Dupuis, Mark O Goodarzi, Xiuqing Guo, Natalie R Hasbani, Adam Heath, Bertha Hidalgo, Marguerite R Irvin, W Craig Johnson, Rita R Kalyani, Leslie Lange, Rozenn N Lemaitre, Ching-Ti Liu, Simin Liu, Jee-Young Moon, Rami Nassir, James S Pankow, Mary Pettinger, Laura M Raffield, Laura J Rasmussen-Torvik, Elizabeth Selvin, Mackenzie K Senn, Aladdin H Shadyab, Albert V Smith, Nicholas L Smith, Lyn Steffen, Sameera Talegakwar, Kent D Taylor, Paul S De Vries, James G Wilson, Alexis C Wood, Lisa R Yanek, Jie Yao, Yinan Zheng, Eric Boerwinkle, Alanna C Morrison, Miriam Fornage, Tracy P Russell, Bruce M Psaty, Daniel Levy, Nancy L Heard-Costa, Vasan S Ramachandran, Rasika A Mathias, Donna K Arnett, Robert Kaplan, Kari E North, Adolfo Correa, April Carson, Jerome I Rotter, Stephen S Rich, Joann E Manson, Alexander P Reiner, Charles Kooperberg, Jose C Florez, James B Meigs, Jordi Merino, Deirdre K Tobias, Han Chen, Alisa K Manning

Faculty, Staff and Student Publications

Few studies have demonstrated reproducible gene-diet interactions (GDIs) impacting metabolic disease risk factors, likely due in part to measurement error in dietary intake estimation and insufficient capture of rare genetic variation. We aimed to identify GDIs across the genetic frequency spectrum impacting the macronutrient-glycemia relationship in genetically and culturally diverse cohorts. We analyzed 33,187 participants free of diabetes from 10 National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program cohorts with whole-genome sequencing, self-reported diet, and glycemic trait data. We fit cohort-specific, multivariable-adjusted linear mixed models for the effect of diet, modeled as an isocaloric substitution of carbohydrate …

Identification Of Dietary Supplements Associated With Blood Metabolites In The Hispanic Community Health Study/Study Of Latinos Cohort Study, Robert C Kaplan, Jessica S Williams-Nguyen, Yuhan Huang, Yasmin Mossavar-Rahmani, Bing Yu, Eric Boerwinkle, Marc D Gellman, Martha Daviglus, Aisha Chilcoat, Linda Van Horn, Kim Faurot, Qibin Qi, Heather Greenlee

Faculty, Staff and Student Publications

BACKGROUND: Metabolomics approaches have been widely used to define the consumption of foods but have less often been used to study exposure to dietary supplements.

OBJECTIVES: This study aimed to identify dietary supplements associated with metabolite levels and to examine whether these metabolites predicted incident diabetes risk.

METHODS: We studied 3972 participants from a prospective cohort study of 18-74-y-old Hispanic/Latino adults. At a baseline examination, we ascertained use of dietary supplements using recall methods and concurrently, a serum metabolomic panel. After adjustment for potential confounders, we identified dietary supplements associated with metabolites. We then examined the association of these metabolites …

Exploration Of Associations Among Dietary Tryptophan, Microbiome Composition And Function, And Symptom Severity In Irritable Bowel Syndrome, Anna M Plantinga, Kendra J Kamp, Qinglong Wu, Li Chen, Linda Yoo, Robert L Burr, Kevin C Cain, Daniel Raftery, Fausto Carnevale Neto, Shyam Badu, Sik Yu So, Tor Savidge, Robert J Shulman, Margaret M Heitkemper

Faculty, Staff and Students Publications

BACKGROUND: Imbalance of the tryptophan (TRP) pathway may influence symptoms among patients with irritable bowel syndrome (IBS). This study explored relationships among different components that contribute to TRP metabolism (dietary intake, stool metabolite levels, predicted microbiome metabolic capability) in females with IBS and healthy controls (HCs). Within the IBS group, we also investigated relationships between TRP metabolic determinants, Bifidobacterium abundance, and symptoms of IBS.

METHODS: Participants with IBS (Rome III) and HCs completed a 28-day diary of gastrointestinal symptoms and a 3-day food record for TRP intake. They provided a stool sample for shotgun metagenomics, 16 S rRNA analyses, and …

The Prevalence And Determinants Of Nafld And Mafld And Their Severity In The Va Primary Care Setting, Aaron P Thrift, Theresa H Nguyen, Codey Pham, Maya Balakrishnan, Fasiha Kanwal, Rohit Loomba, Hao T Duong, David Ramsey, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND & AIMS: A recent panel of international experts proposed the disease acronym metabolic (dysfunction)-associated fatty liver disease (MAFLD) in lieu of nonalcoholic fatty liver disease (NAFLD). We aimed to estimate the burden of and risk factors for NAFLD and MAFLD, and to examine the concordance between definitions in a Veterans population.

METHODS: We conducted a cross-sectional study among randomly selected patients within primary care at the Houston Veterans Affairs (VA) facility. Participants completed a survey, provided blood, and underwent Fibroscan. In the absence of heavy alcohol, hepatitis C virus and hepatitis B virus, a controlled attenuation parameter median ≥290 …

Human Papillomavirus Vaccination Prevalence And Disproportionate Cancer Burden Among Us Veterans, Smrithi Chidambaram, Su-Hsin Chang, Vlad C Sandulache, Angela L Mazul, Jose P Zevallos

Faculty, Staff and Students Publications

This cross-sectional study examines the rate of HPV vaccination and the number eligible for this vaccination among younger veterans and civilians.

Evaluation Of Retinal Nerve Fibre Layer Thickness As A Possible Measure Of Diabetic Retinal Neurodegeneration In The Epic-Norfolk Eye Study, Sidra Zafar, Kristen A Staggers, Jie Gao, Yao Liu, Praveen J Patel, Paul J Foster, Benjamin J Frankfort, Michael Abramoff, Charles G Minard, Alasdair Warwick, Anthony P Khawaja, Roomasa Channa

Faculty, Staff and Students Publications

BACKGROUND/AIMS: Markers to clinically evaluate structural changes from diabetic retinal neurodegeneration (DRN) have not yet been established. To study the potential role of peripapillary retinal nerve fibre layer (pRNFL) thickness as a marker for DRN, we evaluated the relationship between diabetes, as well as glycaemic control irrespective of diabetes status and pRNFL thickness.

METHODS: Leveraging data from a population-based cohort, we used general linear mixed models (GLMMs) with a random intercept for patient and eye to assess the association between pRNFL thickness (measured using GDx) and demographic, systemic and ocular parameters after adjusting for typical scan score. GLMMs were also …

Specific Causes Of Excess Late Mortality And Association With Modifiable Risk Factors Among Survivors Of Childhood Cancer: A Report From The Childhood Cancer Survivor Study Cohort, Stephanie B Dixon, Qi Liu, Eric J Chow, Kevin C Oeffinger, Paul C Nathan, Rebecca M Howell, Wendy M Leisenring, Matthew J Ehrhardt, Kirsten K Ness, Kevin R Krull, Ann C Mertens, Melissa M Hudson, Leslie L Robison, Yutaka Yasui, Gregory T Armstrong

Faculty, Staff and Student Publications

Background: 5-year survival after childhood cancer does not fully describe life-years lost due to childhood cancer because there are a large number of deaths occurring beyond 5-years (late mortality) related to cancer and cancer treatment. Specific causes of health-related (non-recurrence, non-external) late mortality and risk reduction through modifiable lifestyle and cardiovascular risk factors are not well described. Through using a well-characterised cohort of 5-year survivors of the most common childhood cancers, we evaluated specific health-related causes of late mortality and excess deaths compared with the general US population and identified targets to reduce future risk.

Methods: In this multi-institutional, hospital-based, …

A Precision Environmental Health Approach To Prevention Of Human Disease, Andrea Baccarelli, Dana C Dolinoy, Cheryl Lyn Walker

Faculty, Staff and Students Publications

Human health is determined by the interaction of our environment with the genome, epigenome, and microbiome, which shape the transcriptomic, proteomic, and metabolomic landscape of cells and tissues. Precision environmental health is an emerging field leveraging environmental and system-level ('omic) data to understand underlying environmental causes of disease, identify biomarkers of exposure and response, and develop new prevention and intervention strategies. In this article we provide real-life illustrations of the utility of precision environmental health approaches, identify current challenges in the field, and outline new opportunities to promote health through a precision environmental health framework.

Cdk5-Prmt1-Wdr24 Signaling Cascade Promotes Mtorc1 Signaling And Tumor Growth, Shasha Yin, Liu Liu, Lauren E Ball, Yalong Wang, Mark T Bedford, Stephen A Duncan, Haizhen Wang, Wenjian Gan

Faculty, Staff and Student Publications

The mammalian target of rapamycin complex1 (mTORC1) is a central regulator of metabolism and cell growth by sensing diverse environmental signals, including amino acids. The GATOR2 complex is a key component linking amino acid signals to mTORC1. Here, we identify protein arginine methyltransferase 1 (PRMT1) as a critical regulator of GATOR2. In response to amino acids, cyclin-dependent kinase 5 (CDK5) phosphorylates PRMT1 at S307 to promote PRMT1 translocation from nucleus to cytoplasm and lysosome, which in turn methylates WDR24, an essential component of GATOR2, to activate the mTORC1 pathway. Disruption of the CDK5-PRMT1-WDR24 axis suppresses hepatocellular carcinoma (HCC) cell proliferation …

Association Of Radiotherapy Duration With Clinical Outcomes In Patients With Esophageal Cancer Treated In Nrg Oncology Trials: A Secondary Analysis Of Nrg Oncology Randomized Clinical Trials, Christopher L. Hallemeier, Jennifer Moughan, Michael G. Haddock, Arnold M. Herskovic, Bruce D. Minsky, Mohan Suntharalingam, Kenneth L. Zeitzer, Madhur K. Garg, Bruce D. Greenwald, Ritsuko U. Komaki, Lindsay L. Puckett, Hyun Kim, Shane Lloyd, David A. Bush, Harold E. Kim, Thomas E. Lad, Joshua E. Meyer, Gordon S. Okawara, Adam Raben, Tracey E. Schefter, Jerry L. Barker, Carla I. Falkson, Gregory M.M. Videtic, Rojymon Jacob, Kathryn A. Winter, Christopher H. Crane

Einstein Health Papers

IMPORTANCE: For many types of epithelial malignant neoplasms that are treated with definitive radiotherapy (RT), treatment prolongation and interruptions have an adverse effect on outcomes.

OBJECTIVE: To analyze the association between RT duration and outcomes in patients with esophageal cancer who were treated with definitive chemoradiotherapy (CRT).

DESIGN, SETTING, AND PARTICIPANTS: This study was an unplanned, post hoc secondary analysis of 3 prospective, multi-institutional phase 3 randomized clinical trials (Radiation Therapy Oncology Group [RTOG] 8501, RTOG 9405, and RTOG 0436) of the National Cancer Institute-sponsored NRG Oncology (formerly the National Surgical Adjuvant Breast and Bowel Project, RTOG, and Gynecologic Oncology …

Neoadjuvant Pembrolizumab In Localized Microsatellite Instability High/Deficient Mismatch Repair Solid Tumors, Kaysia Ludford, Won Jin Ho, Jane V Thomas, Kanwal P S Raghav, Mariela Blum Murphy, Nicole D Fleming, Michael S Lee, Brandon G Smaglo, Y Nancy You, Matthew M Tillman, Carlos Kamiya-Matsuoka, Selvi Thirumurthi, Craig Messick, Benny Johnson, Eduardo Vilar, Arvind Dasari, Sarah Shin, Alexei Hernandez, Xuan Yuan, Hongqui Yang, Wai Chin Foo, Wei Qiao, Dipen Maru, Scott Kopetz, Michael J Overman

Faculty, Staff and Student Publications

PURPOSE: Pembrolizumab significantly improves clinical outcomes in advanced/metastatic microsatellite instability high (MSI-H)/deficient mismatch repair (dMMR) solid tumors but is not well studied in the neoadjuvant space.

METHODS: This is a phase II open-label, single-center trial of localized unresectable or high-risk resectable MSI-H/dMMR tumors. Treatment is pembrolizumab 200 mg once every 3 weeks for 6 months followed by surgical resection with an option to continue therapy for 1 year followed by observation. To continue on study, patients are required to have radiographic or clinical benefit. The coprimary end points are safety and pathologic complete response. Key secondary end points are response …

Zoster-Associated Prothrombotic Plasma Exosomes And Increased Stroke Risk, Andrew N Bubak, Christina Coughlan, Janelle Posey, Anthony J Saviola, Christy S Niemeyer, Serena W R Lewis, Sara Bustos Lopez, Adriana Solano, Stephen K Tyring, Cassidy Delaney, Keith B Neeves, Ravi Mahalingam, Kirk C Hansen, Maria A Nagel

Faculty, Staff and Student Publications

Herpes zoster (HZ; shingles) caused by varicella zoster virus reactivation increases stroke risk for up to 1 year after HZ. The underlying mechanisms are unclear, however, the development of stroke distant from the site of zoster (eg, thoracic, lumbar, sacral) that can occur months after resolution of rash points to a long-lasting, virus-induced soluble factor (or factors) that can trigger thrombosis and/or vasculitis. Herein, we investigated the content and contributions of circulating plasma exosomes from HZ and non-HZ patient samples. Compared with non-HZ exosomes, HZ exosomes (1) contained proteins conferring a prothrombotic state to recipient cells and (2) activated platelets …