Digital Commons Network^™

Spending Changes After Moving To Areas With Greater Aco Participation Among Nonattributed Medicare Beneficiaries, Yucheng Hou, Marisa Elena Domino, Valerie A Lewis, Qing Gong, Kevin Callison, Justin G Trogdon

Faculty, Staff and Student Publications

IMPORTANCE: Accountable care organizations (ACOs) under the Medicare Shared Savings Program have long been envisioned as a pathway to improved care efficiency and quality of care for all Medicare beneficiaries. However, little is known about whether the changes in health care spending associated with ACOs have extended beyond ACO-attributed Medicare beneficiaries to all Medicare beneficiaries.

OBJECTIVE: To estimate spending changes by non-ACO-attributed Medicare beneficiaries after moving to geographic areas with greater ACO participation.

DESIGN, SETTING, AND PARTICIPANTS: This repeated cross-sectional study analyzed claims from a 20% representative sample of all Medicare beneficiaries, aged 65 to 99 years, from 2009 to …

Sleep Trajectories And All-Cause Mortality Among Low-Income Adults, Kelsie M Full, Hui Shi, Loren Lipworth, Lawrence T Dauer, Michael T Mumma, Qian Xiao

Faculty, Staff and Student Publications

IMPORTANCE: Short and long sleep durations are adversely associated with cardiovascular disease (CVD), type 2 diabetes, and mortality. It remains unclear how sleep duration trajectories over time are associated with mortality and whether these associations vary by well-documented sex, race, and socioeconomic sleep disparities.

OBJECTIVE: To investigate the association of 5-year sleep duration trajectories with all-cause and cause-specific mortality among US adults, predominantly those in low-income groups.

DESIGN, SETTING, AND PARTICIPANTS: The Southern Community Cohort Study included participants aged 40 to 79 years recruited and enrolled (from March 2002 to September 2009) from community health centers by using random sampling …

Characterizing The Genetic Basis For Inherited Retinal Disease: Lessons Learned From The Foundation Fighting Blindness Clinical Consortium's Gene Poll, Kari Branham, Lassana Samarakoon, Isabelle Audo, Allison R Ayala, Janet K Cheetham, Stephen P Daiger, Patty Dhooge, Jacque L Duncan, Todd A Durham, Abigail T Fahim, Rachel M Huckfeldt, Robert B Hufnagel, Susanne Kohl, Ramiro S Maldonado, Michele Melia, Michel Michaelides, Mark E Pennesi, José-Alain Sahel, Juliana M Ferraz Sallum, Mandeep S Singh, Dror Sharon, Kimberly Stepien, Kaylie Jones, Christina Y Weng

Faculty, Staff and Students Publications

PURPOSE: The Foundation Fighting Blindness (FFB) Consortium is a collaboration of 41 international clinical centers that manage patients affected with inherited retinal diseases (IRDs). The annual Consortium gene poll was initiated in 2020 to capture the genetic cause of disease in patients with IRD and associated clinical practices of Consortium sites. Data from the 2022 gene poll are reported here.

METHODS: In 2022, academic, private practice, and government ophthalmology clinics that are members of the Consortium centers were polled to identify per-case IRD genetic causality from a list of 387 syndromic and nonsyndromic IRD genes. The survey also assessed how …

Safety And Tolerability Of Letetresgene Autoleucel (Gsk3377794): Pilot Studies In Patients With Advanced Non-Small Cell Lung Cancer, Mehmet Altan, Gilberto Lopes, T Jeroen N Hiltermann, Ramaswamy Govindan, Liza C Villaruz, Emiliano Calvo, Martin J Edelman, Muhammad Furqan, Joel Neal, Enriqueta Felip, Jennifer W Carlisle, John V Heymach, Róisín Eilish O'Cearbhaill, Marjorie Zauderer, Michael Chisamore, Ellie Corigliano, Ioanna Eleftheriadou, Stefan Zajic, Ben Jenkins, Sophia Goodison, Sunil Suchindran, Natalia Ramos-Hernandez, Nidale Tarek, Adam J Schoenfeld

Faculty, Staff and Student Publications

Purpose: The study aims to evaluate the safety, tolerability, and antitumor response of letetresgene autoleucel (lete-cel), genetically modified autologous T cells expressing a T-cell receptor specific for New York esophageal squamous cell carcinoma 1 (NY-ESO-1)/LAGE-1a shared epitope, alone or in combination with pembrolizumab, in HLA-A*02-positive (HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06) patients with NY-ESO-1- and/or LAGE-1a-positive non-small cell lung cancer.

Patients and methods: Study 208749 was a single-arm study of lete-cel alone. Study 208471 was a multiarm study of lete-cel alone or in combination with pembrolizumab in patients with advanced or recurrent non-small cell lung cancer.

Results: More than 2,500 patients were …

Short Duration Of Antenatal Corticosteroid Exposure And Outcomes In Extremely Preterm Infants, Sanjay Chawla, Myra H Wyckoff, Satyan Lakshminrusimha, Matthew A Rysavy, Ravi Mangal Patel, Dhuly Chowdhury, Abhik Das, Rachel G Greenberg, Girija Natarajan, Seetha Shankaran, Edward F Bell, Namasivayam Ambalavanan, Noelle E Younge, Abbot R Laptook, Leeann R Pavlek, Carl H Backes, Krisa P Van Meurs, Erika F Werner, Waldemar A Carlo, National Institute Of Child Health And Human Development (Nichd) Neonatal Research Network (Nrn)

Faculty, Staff and Student Publications

Importance: When preterm delivery is imminent, it remains unclear whether the timing from administration of antenatal betamethasone to birth may reduce mortality and morbidity among extremely preterm infants.

Objective: To evaluate the association of duration from exposure to first dose of antenatal betamethasone with outcomes among extremely preterm infants.

Design, setting, and participants: This cohort study enrolled infants born at 22 0/7 to 27 6/7 weeks' gestation from January 2016 to February 2021 at National Institute of Child Health and Human Development Neonatal Research Network centers. Infants exposed to multiple doses of antenatal betamethasone, infants who did not receive intensive …

Phase I/Ii Study Of The Aurora Kinase A Inhibitor Alisertib And Pembrolizumab In Refractory, Rb-Deficient Head And Neck Squamous Cell Carcinomas, Faye M Johnson, Madison P O'Hara, Lacin Yapindi, Peixin Jiang, Hai T Tran, Alexandre Reuben, Weihong Xiao, Maura L Gillison, Xiaowen Sun, Alexander Khalaf, J Jack Lee, Jagannadha K Sastry, Soma Ghosh

Faculty, Staff and Student Publications

Purpose: Effective therapy for recurrent head and neck squamous cell carcinoma (HNSCC) that is refractory to chemotherapy and immunotherapy is a considerable need. Aurora kinase A inhibition leads to apoptosis and immunogenic cell death in preclinical models of human papilloma virus (HPV)-driven cancers.

Patients and methods: Alisertib was administered orally twice daily on days 1-7 and pembrolizumab on day 1 of a 21-day cycle to adults with advanced solid tumors (phase I) or with immunotherapy- and platinum-resistant, HPV-positive HNSCC (phase II).

Results: The recommended phase II alisertib dose was 40 mg, which had only the expected toxicity including cytopenia that …

The Landscape Of Ctdna In Appendiceal Adenocarcinoma, Michael G White, Mohammad A Zeineddine, Eleanor A Fallon, Fadl A Zeineddine, Julia Dansby, Saikat Chowdhury, Nicholas Hornstein, Abdelrahman Yousef, Mahmoud Yousef, Neal Bhutiani, Yue Gu, Bryan Kee, Arvind Dasari, Michael J Overman, Kanwal Raghav, Scott Kopetz, Abhineet Uppal, Melissa Taggart, Timothy Newhook, Keith Fournier, Beth Helmink, Leylah M Drusbosky, John Paul Shen

Faculty, Staff and Student Publications

Purpose: Appendiceal adenocarcinoma is a rare malignancy with distinct histopathologic subtypes and a natural history with metastasis primarily limited to the peritoneum. Little is known about the molecular pathogenesis of appendiceal adenocarcinoma relative to common tumors.

Experimental design: We analyzed molecular data for patients within the Guardant Health database with appendix cancer (n = 718). We then identified patients with appendiceal adenocarcinoma at our institution (from October 2004-September 2022) for whom ctDNA mutation profiling (liquid biopsy) was performed (n = 168) and extracted clinicopathologic and outcomes data. Of these 168 patients, 57 also had tissue-based tumor mutational profiling, allowing for …

Dairy Consumption And The Colonic Mucosa-Associated Gut Microbiota In Humans-A Preliminary Investigation, Ellie Chen, Nadim J Ajami, Donna L White, Yanhong Liu, Shawn Gurwara, Kristi Hoffman, David Y Graham, Hashem B El-Serag, Joseph F Petrosino, Li Jiao

Faculty, Staff and Students Publications

Background: Dairy consumption has been associated with various health outcomes that may be mediated by changes in gut microbiota.

Methods: This cross-sectional study investigated the association between the colonic mucosa-associated gut microbiota and the self-reported intake of total dairy, milk, cheese, and yogurt. A total of 97 colonic mucosal biopsies collected from 34 polyp-free individuals were analyzed. Dairy consumption in the past year was assessed using a food frequency questionnaire. The 16S rRNA gene V4 region was amplified and sequenced. Operational taxonomic unit (OTU) classification was performed using the UPARSE and SILVA databases. OTU diversity and relative abundance were compared …

Arginine Metabolism Is A Biomarker Of Red Blood Cell And Human Aging., Julie A Reisz, Eric J Earley, Travis Nemkov, Alicia Key, Daniel Stephenson, Gregory R Keele, Monika Dzieciatkowska, Steven L Spitalnik, Eldad A Hod, Steven Kleinman, Nareg H Roubinian, Mark T Gladwin, Kirk C Hansen, Philip J Norris, Michael P Busch, James C Zimring, Gary Churchill, Grier P Page, Angelo D'Alessandro

Faculty Research 2025

Increasing global life expectancy motivates investigations of molecular mechanisms of aging and age-related diseases. This study examines age-associated changes in red blood cells (RBCs), the most numerous host cell in humans. Four cohorts, including healthy individuals and patients with sickle cell disease, were analyzed to define age-dependent changes in RBC metabolism. Over 15,700 specimens from 13,757 humans were examined, a major expansion over previous studies of RBCs in aging. Multi-omics approaches identified chronological age-related alterations in the arginine pathway with increased arginine utilization in RBCs from older individuals. These changes were consistent across healthy and sickle cell disease cohorts and …

Activin E Is A New Guardian Protecting Against Hepatic Steatosis Via Inhibiting Lipolysis In White Adipose Tissue., Shi-Young Park, Yoonil Cho, Sae-Mi Son, Jang Ho Hur, Yeongmin Kim, Hyunhee Oh, Hui-Young Lee, Sungwon Jung, Sanghee Park, Il-Young Kim, Se-Jin Lee, Cheol Soo Choi

Faculty Research 2025

Hepatic endoplasmic reticulum (ER) stress is implicated in the development of steatosis and its progression to nonalcoholic steatohepatitis (NASH). The ER in the liver can sustain metabolic function by activating defense mechanisms that delay or prevent the progression of nonalcoholic fatty liver disease (NAFLD). However, the precise mechanisms by which the ER stress response protects against NAFLD remain largely unknown. Recently, activin E has been linked to metabolic diseases such as insulin resistance and NAFLD. However, the physiological conditions and regulatory mechanisms driving hepatic Inhbe expression (which encodes activin E) as well as the metabolic role of activin E in …

Patient-Reported Outcomes: Comparing Functional Avoidance And Standard Thoracic Radiation Therapy In Lung Cancer, Spencer Poiset, Joseph Lombardo, Edward Castillo, Richard Castillo, Bernard Jones, Moyed Miften, Brian Kavanagh, Adam Dicker, Cullen Boyle, Nicole Simone, Benjamin Movsas, Inga Grills, Chad Rusthoven, Yevgeniy Vinogradskiy, Lydia Wilson

Department of Radiation Oncology Faculty Papers

PURPOSE: Novel methods generate functional images using image processing techniques combined with four-dimensional computed tomography (4DCT) data (4DCT-ventilation). 4DCT-ventilation was implemented in a phase II, multicenter functional avoidance clinical trial. The work compares functional avoidance patient-reported outcomes (PROs) against historical standards.

METHODS: Patients with locally advanced lung cancer undergoing curative-intent chemoradiation were accrued. 4DCT-ventilation imaging was generated and functional avoidance treatment plans created reduced dose to functional lung. PRO instruments included Functional Assessment of Cancer Therapy Lung questionnaire and accompanying subscales (including the Trial Outcome Index [TOI]), EuroQol-5 Dimension (EQ-5D), and EQ-Visual Analog Scale (EQ-VAS). The average change from baseline …

Synaptic Alterations In Pyramidal Cells Following Genetic Manipulation Of Neuronal Excitability In Monkey Prefrontal Cortex, Guillermo Gonzalez-Burgos, Takeaki Miyamae, Yosuke Nishihata, Olga L Krimer, Kirsten Wade, Kenneth N Fish, Dominique Arion, Zhao-Lin Cai, Mingshan Xue, William R Stauffer, David A Lewis

Duncan NRI Faculty and Staff Publications

The primate dorsolateral prefrontal cortex (DLPFC) displays unique in vivo activity patterns, but how in vivo activity regulates DLPFC pyramidal neuron (PN) properties remains unclear. We assessed the effects of in vivo Kir2.1 overexpression, a genetic silencing tool, on synapses in monkey DLPFC PNs. We show for the first time that recombinant ion channel expression successfully modifies the excitability of primate cortex neurons, producing effects on synaptic properties apparently different from those in the rodent cortex.

The Effects Of Burst Steroid Therapy On Short-Term Decongestion In Acute Heart Failure Patients With Pro-Inflammatory Activation: A Post Hoc Analysis Of The Cortahf Randomized, Open-Label, Pilot Trial, Jan Biegus, Douglas L Mann, Et Al.

2020-Current year OA Pubs

BACKGROUND: The effect of steroids on congestion in patients with acute heart failure (AHF) is not known.

METHODS AND RESULTS: Patients with AHF, NT-proBNP levels > 1500 pg/mL and high-sensitivity C-reactive protein (hsCRP) levels > 20 mg/L were randomized to once-daily oral 40 mg prednisone for 7 days or usual care. In this post hoc analysis, congestion score was calculated on the basis of orthopnea, edema and rales (0 reflecting lack of congestion, and 9 maximal congestion) at each time point. Among 100 eligible patients randomized, those assigned to prednisone had a greater improvement in congestion score at day 31 (win odds …

Association Between Early Immunosuppression Center Variability And One-Year Outcomes After Pediatric Liver Transplant., Vikram K. Raghu, Scott D. Rothenberger, James E. Squires, Elizabeth Eisenberg, Anna L. Peters, Jennifer Halma, Swati Antala, Irini D. Batsis, Ke-You Zhang, Amy G. Feldman, Daniel H. Leung, Steven J. Lobritto, John Bucuvalas, Simon P. Horslen, George V. Mazariegos, Emily R. Perito

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Despite the existence of institutional protocols, liver transplant centers often have variability in early immunosuppression practices. We aimed to measure within-center variability in early immunosuppression after pediatric liver transplant (LT) and examine its association with one-year outcomes.

METHODS: We analyzed pediatric LTs from 2013 to 2018 in the United Network for Organ Sharing registry, with data aggregated by center. We categorized induction regimen as corticosteroids only vs. T-cell depleting antibody vs. non-T-cell depleting antibody. Primary exposures were coefficient of immunosuppression variability (CIV) in (1) induction and (2) mycophenolate mofetil (MMF) use. Primary outcomes were one-year graft survival, patient survival, …

Tofersen Treatment Leads To Sustained Stabilization Of Disease In Sod1 Als In A "Real-World" Setting, Sean E Smith, Kelly Mccoy-Gross, Amber Malcolm, Jeri Oranski, Jesse W Markway, Timothy M Miller, Robert C Bucelli

2020-Current year OA Pubs

OBJECTIVE: Patients with amyotrophic lateral sclerosis (ALS) caused by superoxide dismutase 1 (SOD1) gene mutations (SOD1 ALS) treated with tofersen have shown slowing of disease progression, and disease stabilization with recovery of function in some patients. We report our clinical experience with treating patients with SOD1 ALS and the effects of tofersen on outcome measures.

METHODS: This was a single-center observational study of patients with SOD1 ALS receiving treatment with tofersen. The effects of tofersen treatment on neurofilament levels, muscle strength, and clinical outcome measures were assessed. Several patients had outpatient neuromuscular rehabilitation in addition to tofersen treatment and we …

Prospective Observational Study Of Fkrp-Related Limb-Girdle Muscular Dystrophy R9: A Grasp Consortium Study, Lindsay N Alfano, Stephanie Hunn, Conrad C Weihl, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Limb-girdle muscular dystrophy R9 (LGMDR9, formerly known as LGMD2I), caused by variants in the fukutin-related protein (FKRP) gene leads to progressive muscle weakness of the shoulder and pelvic limb-girdles and loss of motor function over time. Clinical management and future trial design are improved by determining which standardized clinical outcome assessments (COA) of function are most appropriate to capture disease presentation and progression, informing endpoint selection and enrollment criteria. The purpose of our study was to evaluate the cross-sectional validity and reliability of clinical outcome assessments in patients with FKRP-related LGMDR9 participating in the Genetic Resolution and Assessments Solving …

Antiseizure Medication Prescribing In People With Dravet Syndrome: An Analysis Of Real-Time Administrative Data, Kevin Y Xu, Binx Yezhe Lin, M Scott Perry, Fábio A Nascimento

2020-Current year OA Pubs

Since 2018, three new antiseizure medications (ASMs) received FDA approval for Dravet syndrome (DS) in the U.S: cannabidiol, stiripentol, and fenfluramine. Yet, the uptake of these ASMs in routine clinical practice is unknown. We use new ICD-10 codes for DS (implemented in 2020) to estimate ASM receipt in patients with DS. We analyzed the TriNetX Network, a real-time electronic health record-based dataset linked to prescription data encompassing all 50 states of the U.S. After identifying patients with health care encounters for DS in 2021 and 2022 (via ICD-10 codes), we examined ASM prescribing in the year following a DS claim: …

Perinatal Arterial Ischemic Stroke Diagnosed In Infants Receiving Therapeutic Hypothermia For Hypoxic-Ischemic Encephalopathy, Fernando F Gonzalez, Sarah E Monsell, Marie-Coralie Cornet, Hannah Glass, Jessica Wisnowski, Amit Mathur, Robert Mckinstry, Yi Li, Tai-Wei Wu, Dennis E Mayock, Patrick J Heagerty, Sandra E Juul, Yvonne W Wu

2020-Current year OA Pubs

BACKGROUND: Both perinatal arterial ischemic stroke (PAIS) and hypoxic-ischemic encephalopathy (HIE) can present with neonatal encephalopathy. We hypothesized that among infants undergoing therapeutic hypothermia, presence of PAIS is associated with a higher risk of seizures and a lower risk of persistent encephalopathy after rewarming.

METHODS: We studied 473 infants with moderate or severe HIE enrolled in the HEAL Trial who received a brain MRI. We defined PAIS as focal ischemic infarct(s) within an arterial distribution, and HIE pattern of brain injury as central gray, peripheral watershed, or global injury. We compared the risk of seizures (clinically suspected or electrographic), and …

Cross-Sectional Comparison Of Structural Mri Markers Of Impairment In A Diverse Cohort Of Older Adults, Julie K Wisch, Kalen Petersen, Peter R Millar, Omar Abdelmoity, Ganesh M Babulal, Karin L Meeker, Meredith N Braskie, Kristine Yaffe, Arthur W Toga, Sid O'Bryant, Beau M Ances, Habs‐Hd Study Team

2020-Current year OA Pubs

Neurodegeneration is presumed to be the pathological process measure most proximal to clinical symptom onset in Alzheimer Disease (AD). Structural MRI is routinely collected in research and clinical trial settings. Several quantitative MRI-based measures of atrophy have been proposed, but their low correspondence with each other has been previously documented. The purpose of this study was to identify which commonly used structural MRI measure (hippocampal volume, cortical thickness in AD signature regions, or brain age gap [BAG]) had the best correspondence with the Clinical Dementia Rating (CDR) in an ethno-racially diverse sample. 2870 individuals recruited by the Healthy and Aging …

Sex-Specific Divergences In The Types And Timing Of Infiltrating Immune Cells During The Intervertebral Disc Acute Injury Response And Their Associations With Degeneration, Sade W Clayton, Remy E Walk, Laura Mpofu, Garrett W D Easson, Simon Y Tang

2020-Current year OA Pubs

OBJECTIVE: Inadequate repair of the intervertebral disc (IVD) contributes to low back pain. Infiltrating immune cells into damaged tissues are critical mediators of repair, yet little is known about the identities, roles, and temporal regulation following IVD injury. By analyzing transcripts of immune cell markers, histopathologic analysis, immunofluorescence, and flow cytometry, we aimed to define the temporal cascade of infiltrating immune cells and their associations with IVD degeneration.

METHODS: Caudal IVDs from 12-week-old C57BL6/J mice were injured and monitored for 42 days post-injury. Transcriptional markers identifying myeloid, B, and T immune cells, and angiogenic factors were measured from the IVDs …

Cracking The Pericellular Matrix Code: Exploring How Mmp-2, -3, And -7 Influence Matrix Breakdown And Biomechanical Properties, Benjamin Tizian Baumann, Jule Nieuwstraten, Christian Konrads, Farshid Guilak, Marina Danalache

2020-Current year OA Pubs

INTRODUCTION: The intricate process of articular cartilage remodeling, pivotal for both physiological functions and osteoarthritis (OA) progression, is orchestrated through a balance of matrix synthesis and breakdown, which is mediated by matrix metalloproteinase enzymes (MMPs). At the heart of this remodeling lies the pericellular matrix (PCM), a specialized microenvironment encapsulating each chondrocyte and composed mainly of collagen type VI and perlecan. The aim of this study was to assess the impact of MMP-2, -3, and -7 on the structural integrity and biomechanical attributes of the PCM.

METHODS: Human articular cartilage explants (N = 10 patients) were incubated with activated MMP-2, …

Two Cardinal Features Of Als, Reduced Stmn2 And Pathogenic Tdp-43, Synergize To Accelerate Motor Decline In Mice, Kelsey L Krus, Ana Morales Benitez, Amy Strickland, Jeffrey Milbrandt, A Joseph Bloom, Aaron Diantonio

2020-Current year OA Pubs

Pathological TDP-43 loss from the nucleus and cytoplasmic aggregation occurs in almost all cases of ALS and half of frontotemporal dementia patients. Stathmin2 (Stmn2) is a key target of TDP-43 regulation and aberrantly spliced Stmn2 mRNA is found in patients with ALS, frontotemporal dementia, and Alzheimer's Disease. STMN2 participates in the axon injury response and its depletion in vivo partially replicates ALS-like symptoms including progressive motor deficits and distal NMJ denervation. The interaction between STMN2 loss and TDP-43 dysfunction has not been studied in mice because TDP-43 regulates human but not murine Stmn2 splicing. Therefore, we generated trans-heterozygous mice that …

Presentation And Surgical Outcomes Of Primary Hyperparathyroidism After Radioactive Iodine Therapy, Shaleen V Sathe, Blake Sparkman, Evan Bernard, Eileen R Smith, Kevin He, Alexander Chiu, Taylor C Brown

2020-Current year OA Pubs

BACKGROUND: Radioactive iodine (RAI) is a common treatment for various thyroid diseases. Previous studies have suggested susceptibility of parathyroid glands to the mutagenic effect of RAI and the development of primary hyperparathyroidism (PHPT). We tested the possible link between prior RAI treatment, disease presentation, and treatment outcomes.

METHODS: A retrospective analysis of 704 individuals who underwent parathyroidectomy for PHPT at a tertiary care center between the years 2015 and 2023 was performed. Preoperative and postoperative parameters, including demographic characteristics, biochemical markers, imaging data, and surgical and pathology findings were collected and analyzed to compare differences in patients who had previous …

National Prescribing Practices For Pediatric Dystonia Among Providers In The United States., Sarah Paige Davis, Natalie J. Kane, Haley E. Botteron, Rose N. Gelineau-Morel

Manuscripts, Articles, Book Chapters and Other Papers

While multiple oral medications are used to treat dystonia, limited information exists on current prescribing practices. This study analyzes real-world prescribing practices for pediatric dystonia in the United States, evaluating prescription frequency, dosing, and the impact of comorbidities. Oracle electronic health record real-world data were queried from 2014 to 2019 for encounters of patients under age 18 with a dystonia diagnosis and available medication records. Information was extracted on prescriptions for dystonia medications (baclofen, clonidine, carbidopa-levodopa, gabapentin, tetrabenazine, trihexyphenidyl, and select benzodiazepines), dosing, and comorbid diagnoses of cerebral palsy (CP), epilepsy, or spasticity. A total of 4010 pediatric patients with …

Benefits And Harms Of Hepatocellular Carcinoma Screening Outreach In Patients With Cirrhosis: A Multicenter Randomized Clinical Trial, Amit G Singal, Darine Daher, Manasa Narasimman, Sruthi Yekkaluri, Yan Liu, Vanessa Cerda, Chaitra Banala, Aisha Khan, Minjae Lee, Karim Seif El Dahan, Caitlin C Murphy, Jennifer R Kramer, Ruben Hernaez

Faculty, Staff and Students Publications

Background: The value of hepatocellular carcinoma screening is defined by the balance of benefits from early tumor detection vs harms because of false-positive results. We evaluated the value of a mailed outreach strategy for hepatocellular carcinoma screening in patients with cirrhosis.

Methods: We conducted a multicenter pragmatic randomized clinical trial comparing mailed outreach for hepatocellular carcinoma screening (n = 1436) and usual care with visit-based screening (n = 1436) among patients with cirrhosis at 3 health systems from March 2018 to September 2021. Outcomes of interest were early stage hepatocellular carcinoma detection (ie, screening benefit) and diagnostic evaluation for false-positive …

Hes V20 Outperforms Galad For Detection Of Hcc: A Phase 3 Biomarker Study In The United States, Hashem B El-Serag, Qingchun Jin, Nabihah Tayob, Emad Salem, Michelle Luster, Abeer Alsarraj, Saira Khaderi, Amit G Singal, Jorge A Marrero, Sumeet K Asrani, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: The original hepatocellular carcinoma early detection screening (HES) score, which combines alpha-fetoprotein (AFP) with age, alanine aminotransferase, and platelets, has better performance than AFP alone for early HCC detection. We have developed HES V2.0 by adding AFP-L3 and des-gamma-carboxy prothrombin to the score and compared its performance to GALAD and ASAP scores among patients with cirrhosis.

APPROACH AND RESULTS: We conducted a prospective-specimen collection, retrospective-blinded-evaluation phase 3 biomarker cohort study in patients with cirrhosis enrolled in imaging and AFP surveillance. True-positive rate (TPR)/sensitivity and false-positive rate for any or early HCC were calculated for GALAD, ASAP, and …

Improving Individualized Rhabdomyosarcoma Prognosis Predictions Using Somatic Molecular Biomarkers, Mark Zobeck, Javed Khan, Rajkumar Venkatramani, M Fatih Okcu, Michael E Scheurer, Philip J Lupo

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Molecular markers increasingly influence risk-stratified treatment selection for pediatric rhabdomyosarcoma (RMS). This study aims to integrate molecular and clinical data to produce individualized prognosis predictions that can further improve treatment selection.

Methods: Clinical variables and somatic mutation data for 20 genes from 641 patients with RMS in the United Kingdom and the United States were used to develop three Cox proportional hazard models for predicting event-free survival (EFS). The Baseline Clinical (BC) model included treatment location, age, fusion status, and risk group. The Gene Enhanced 2 (GE2) model added TP53 and MYOD1 mutations to the BC predictors. The Gene …

Incidence And Survival Of Children And Adolescents With Wilms Tumor, United States, 2001-2020, Andres F Espinoza, Ekene Onwuka, David A Siegel, Shifan Dai, Sanjeev A Vasudevan, Michael E Scheurer, Philip J Lupo

Center for Medical Ethics and Health Policy Staff Publications

Background: Wilms tumor (WT) is the most common pediatric malignancy of the kidney. Past studies describing WT incidence and survival used surveillance data with < 30% of the US population. We evaluated differences in WT incidence and survival comparing demographic groups and tumor characteristics.

Methods: We analyzed new cases of WT among patients aged < 20 years at diagnosis by using incidence data from US Cancer Statistics (USCS) for 2003-2020 and 5-year relative survival (RS) data from the National Program of Cancer Registries (NPCR) for 2001-2019. To assess incidence trends, average annual percent change (AAPC) was calculated by using joinpoint regression. Relative survival (RS) and all-cause survival were calculated overall and by demographic and clinical variables.

Results: During 2003-2020, 8218 cases of WT were reported in USCS, which represented an age-adjusted incidence rate of 5.7 cases per million. Rates were the highest among females (6.3), children aged 0-4 years (17.2), and non-Hispanic Black patients (7.1). Overall, trends remained stable (AAPC = -0.4, 95% CI: -1.4 to 0.4). Among 7567 cases of WT in NPCR, 5-year RS was 92.6%. Patients with the lowest …

Longitudinal Phage-Bacteria Dynamics In The Early Life Gut Microbiome, Michael J Tisza, Richard E Lloyd, Kristi Hoffman, Daniel P Smith, Marian Rewers, Sara J Javornik Cregeen, Joseph F Petrosino

Center for Medical Ethics and Health Policy Staff Publications

Microbial colonization of the human gut occurs soon after birth, proceeds through well-studied phases and is affected by lifestyle and other factors. Less is known about phage community dynamics during infant gut colonization due to small study sizes, an inability to leverage large databases and a lack of appropriate bioinformatics tools. Here we reanalysed whole microbial community shotgun sequencing data of 12,262 longitudinal samples from 887 children from four countries across four years of life as part of the The Environmental Determinants of Diabetes in the Young (TEDDY) study. We developed an extensive metagenome-assembled genome catalogue using the Marker-MAGu pipeline, …

Resilience And Coping: A Qualitative Analysis Of Cognitive And Behavioral Factors In Adults With Osteogenesis Imperfecta, Hannah E Cho, Whitney S Shepherd, Gianna M Colombo, Andrew D Wiese, W Conor Rork, Kristin M Kostick, Dianne Nguyen, Members Of The Bbdc, Chaya N Murali, Marie-Eve Robinson, Sophie C Schneider, Justin H Qian, Brendan Lee, V Reid Sutton, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Purpose: The aim of this qualitative study was to investigate resilience among adults with Osteogenesis Imperfecta (OI).

Materials and methods: Semi-structured interviews were conducted with 15 adults with OI. Transcripts were coded and subsequently abstracted, yielding themes specific to resilience and coping. Interview guides covered broad topics including pain challenges specific to OI, mental health issues related to OI, and priorities for future interventions for individuals with OI.

Results: Participants described resilience in the context of OI as the ability to grow from adversity, adapt to challenges resulting from OI-related injuries, and find identities apart from their condition. Psychological coping …