Medical Specialties Commons^™

Health Literacy And Cumulative Social Disadvantage Are Associated With Survival And Transplant In Patients With Hepatocellular Carcinoma: A Prospective Study, Lauren D Nephew, Susan M Rawl, Allie Carter, Nicole Garcia, Patrick O Monahan, John Holden, Marwan Ghabril, Eleazar Montalvan-Sanchez, Kavish Patidar, Archita P Desai, Eric Orman, Naga Chalasani

Faculty, Staff and Students Publications

OBJECTIVE: To investigate how individual social determinants of health (SDOH) and cumulative social disadvantage (CSD) affect survival and receipt of liver transplant (LT) in patients with hepatocellular carcinoma (HCC).

METHODS: We enrolled 139 adult patients from two Indianapolis hospital systems between June 2019 and April 2022. Structured questionnaires collected SDOH and social risk factor data. We compared SDOH and CSD by race, gender and disease aetiology, assigning one point per adverse SDOH. Multivariable competing risk survival analysis assessed associations between SDOH, CSD, survival and LT receipt.

RESULTS: Black patients experienced higher CSD than white patients in the cohort (5.4±2.5 vs …

Atrial Fibrillation Status And Physical Rehabilitation In Older Patients With Acute Decompensated Heart Failure: An Analysis From The Rehab-Hf Trial, Douglas Corsi, Sean Dikdan, Naman Upadhyay, Haiying Chen, Dalane W Kitzman, Robert Mentz, David J Whellan, Daniel R Frisch

SKMC Student Presentations and Publications

BACKGROUND: The REHAB-HF (Rehabilitation Therapy in Older Acute Heart Failure Patients) trial demonstrated that a transitional, tailored, progressive rehabilitation intervention improved physical function, 6-minute walk distance, frailty, quality-of-life, and depression in older patients hospitalized for acute decompensated heart failure. This analysis assessed the impact of atrial fibrillation (AF) on intervention benefits.

METHODS AND RESULTS: Of 349 enrolled patients hospitalized for acute decompensated heart failure (mean age 72.7±8.1 years), 176 (50.4%) had AF. Participants were randomly assigned to 12-week rehabilitation intervention or attention control. The primary outcome was Short Physical Performance Battery score at 3 months. Participants with AF were older …

Sex Differences In Metabolic Adaptation In Infants With Cyanotic Congenital Heart Disease, Tina O Findley, Ana Carolina Palei, Kyung Serk Cho, Zhongming Zhao, Caleb Shi, Gouri Mahajan, Antonio Francesco Corno, Jorge Salazar, Louise Mccullough

Faculty, Staff and Student Publications

BACKGROUND: Female infants with congenital heart disease (CHD) face significantly higher postoperative mortality rates after adjusting for cardiac complexity. Sex differences in metabolic adaptation to cardiac stressors may be an early contributor to cardiac dysfunction. In adult diseases, hypoxic/ischemic cardiomyocytes undergo a cardioprotective metabolic shift from oxidative phosphorylation to glycolysis which appears to be regulated in a sexually dimorphic manner. We hypothesize sex differences in cardiac metabolism are present in cyanotic CHD and detectable as early as the infant period.

METHODS: RNA sequencing was performed on blood samples (cyanotic CHD cases, n = 11; controls, n = 11) and analyzed …

Oligodendroglial Fatty Acid Metabolism As A Central Nervous System Energy Reserve, Ebrahim Asadollahi, Andrea Trevisiol, Aiman S Saab, Zoe J Looser, Payam Dibaj, Reyhane Ebrahimi, Kathrin Kusch, Torben Ruhwedel, Wiebke Möbius, Olaf Jahn, Jun Yup Lee, Anthony S Don, Michelle-Amirah Khalil, Karsten Hiller, Myriam Baes, Bruno Weber, E Dale Abel, Andrea Ballabio, Brian Popko, Celia M Kassmann, Hannelore Ehrenreich, Johannes Hirrlinger, Klaus-Armin Nave

Duncan NRI Faculty and Staff Publications

Brain function requires a constant supply of glucose. However, the brain has no known energy stores, except for glycogen granules in astrocytes. In the present study, we report that continuous oligodendroglial lipid metabolism provides an energy reserve in white matter tracts. In the isolated optic nerve from young adult mice of both sexes, oligodendrocytes survive glucose deprivation better than astrocytes. Under low glucose, both axonal ATP levels and action potentials become dependent on fatty acid β-oxidation. Importantly, ongoing oligodendroglial lipid degradation feeds rapidly into white matter energy metabolism. Although not supporting high-frequency spiking, fatty acid β-oxidation in mitochondria and oligodendroglial …

Cerebellar Deep Brain Stimulation As A Dual-Function Therapeutic For Restoring Movement And Sleep In Dystonic Mice, Luis E Salazar Leon, Linda H Kim, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Dystonia arises with cerebellar dysfunction, which plays a key role in the emergence of multiple pathophysiological deficits that range from abnormal movements and postures to disrupted sleep. Current therapeutic interventions typically do not simultaneously address both the motor and non-motor symptoms of dystonia, underscoring the necessity for a multi-functional therapeutic strategy. Deep brain stimulation (DBS) is effectively used to reduce motor symptoms in dystonia, with existing parallel evidence arguing for its potential to correct sleep disturbances. However, the simultaneous efficacy of DBS for improving sleep and motor dysfunction, specifically by targeting the cerebellum, remains underexplored. Here, we test the effect …

Medical Students’ Self-Perceived Knowledge And Clinical Comfort With Genetics In Pakistan, Maheen Arshad, Angela Trepanier, S Shahrukh Hashmi, Rizwan Naeem, Saqib Mehmood, Myla Ashfaq

Faculty, Staff and Student Publications

Pakistan has a high rate of genetic disorders and neonatal mortality concurrent with noted lack of genetic counselors and geneticists. To meet the needs of the patient population, the responsibility of providing clinical genetic services falls on general and specialty physicians. However, their education regarding these essential services is not standardized in medical school curricula nor has it ever been evaluated. The purpose of this work is to describe the self-perceived knowledge, clinical comfort, and perspectives of Pakistani medical students toward their medical genetics' education. A web-based survey was distributed electronically to medical schools around the country. The survey comprised …

Preventive Treatment With A Cd73 Small Molecule Inhibitor Enhances Immune Surveillance In K-Ras Mutant Pancreatic Intraepithelial Neoplasia, Lincoln N Strickland, Wendao Liu, Usama Hussein, Nicolette Mardik, Xian Chen, Tingting Mills, Lana A Vornik, Michelle I Savage, Shizuko Sei, John Clifford, Holger K Eltzschig, Powel H Brown, Zhongming Zhao, Florencia Mcallister, Jennifer M Bailey-Lundberg

Faculty, Staff and Student Publications

Immunoprevention is an emerging consideration for solid tumors, including pancreatic ductal adenocarcinoma (PDAC). We and others have shown that Kras mutations in genetic models of spontaneous pancreatic intraepithelial neoplasia (PanIN), which is a precursor to PDAC, results in CD73 expression in the neoplastic epithelium and some populations of infiltrating immune cells, including macrophages and CD8 T cells. CD73 is an ecto-enzyme that converts extracellular adenosine monophosphate to adenosine, a critical immune inhibitory molecule in PDAC. We hypothesized inhibition of CD73 would reduce the incidence of PanIN formation and alter the immune microenvironment. To test our hypothesis, we used the KrasG12D; …

Cost-Effectiveness Of Point Of Care Smoking Cessation Interventions In Oncology Clinics., Kerri A. Mullen, Kelly Hurley, Shelley Hewitson, Joshua Scoville, Alyssa Grant, Kednapa Thavorn, Eshwar Kumar, Graham W. Warren

Markey Cancer Center Faculty Publications

BACKGROUND: We examined the cost-effectiveness of providing systematic smoking cessation interventions to oncology patients at point-of-care.

METHODS: A decision analytic model was completed from the healthcare payer's perspective and included all incident cancer cases involving patients who smoke in New Brunswick, Canada (n = 1040), cancer site stratifications, and risks of mortality, continued smoking, and cancer treatment failure over one year. Usual care (no cessation support) was compared to the standard Ottawa Model for Smoking Cessation (OMSC) intervention, and to OMSC plus unlimited cost-free stop smoking medication (OMSC + SSM), including nicotine replacement therapy, varenicline, or bupropion. Primary outcomes were …

Benefits Of Calorie Restriction In Mice Are Mediated Via Energy Imbalance, Not Absolute Energy Or Protein Intake, Daniel L Smith, Sharon E Mitchell, Maria S Johnson, Victoria K Gibbs, Stephanie Dickinson, Beate Henschel, Rui Li, Kathryn A Kaiser, Daniella E Chusyd, Andrew W Brown, David B Allison, John R Speakman, Tim R Nagy

Children’s Nutrition Research Center Staff Publications

Caloric restriction (CR) results in reduced energy and protein intake, raising questions about protein restriction's contribution to CR longevity benefits. We kept ad libitum (AL)-fed male C57BL/6J mice at 27°C (AL27) and pair-fed (PF) mice at 22°C (22(PF27)). The 22(PF27) group was fed to match AL27 while restricted for calories due to cold-induced metabolism. The 22(PF27) mice had significantly lower body weight, lean mass, fat mass, leptin, IGF-1, and TNF-α levels than AL27 mice (p< 0.001 for all). Manipulations over ~11 weeks resulted in significant differences in body temperature, physical activity, and expression of key genes linked to hunger in the hypothalamus. Survival was significantly greater in 22(PF27) compared to AL27 overall (p< 0.001). CR in the context of equivalent energy and protein intake resulted in hormonal, metabolic, and physiological benefits and extended longevity. Hence, energy imbalance, rather than low energy or protein intake per se, mediates the benefits of CR.

Clonal Hematopoiesis Of Indeterminate Potential Is Associated With Reduced Risk Of Cognitive Impairment In Patients With Chronic Kidney Disease, Cissy Xiao, Manjula Kurella Tamura, Yang Pan, Varun Rao, Celestin Missikpode, Caitlyn Vlasschaert, Tetsushi Nakao, Xiao Sun, Changwei Li, Zhijie Huang, Amanda Anderson, Md Mesbah Uddin, Do-Kyun Kim, Jonathan Taliercio, Rajat Deo, Zeenat Bhat, Dawei Xie, Panduranga Rao, Jing Chen, James P Lash, Jiang He, Pradeep Natarajan, James E Hixson, Kristine Yaffe, Tanika N Kelly, Cric Study Investigators

Faculty, Staff and Student Publications

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) and dementia disproportionately burden patients with chronic kidney disease (CKD). The association between CHIP and cognitive impairment in CKD patients is unknown.

Methods: We conducted time-to-event analyses in up to 1452 older adults with CKD from the Chronic Renal Insufficiency Cohort who underwent CHIP gene sequencing. Cognition was assessed using four validated tests in up to 6 years mean follow-up time. Incident cognitive impairment was defined as a test score one standard deviation below the baseline mean.

Results: Compared to non-carriers, CHIP carriers were markedly less likely to experience impairment in attention (adjusted …

Lps-Induced Whole-Blood Cytokine Production And Depressive Symptoms In Dementia Spousal Caregivers: The Moderating Effect Of Childhood Trauma, Daniel L Argueta, Kelly N Brice, E Lydia Wu-Chung, Michelle A Chen, Vincent D Lai, Jensine Paoletti-Hatcher, Bryan T Denny, Charles Green, Luis D Medina, Paul Schulz, Jennifer Stinson, Cobi Heijnen, Christopher P Fagundes

Faculty, Staff and Student Publications

Dementia spousal caregivers are at risk for adverse mental and physical health outcomes. Caregiver burden, anticipatory grief, and proinflammatory cytokine production may contribute to depressive symptoms among caregivers. People who report childhood trauma are more likely to have exaggerated stress responses that may also contribute to depressive symptoms in adulthood. This study aimed to test whether the relationship between whole-blood cytokine production and depressive symptoms is strongest in caregivers who report high levels of childhood trauma.

Methods: A sample of 103 dementia spousal caregivers provided self-report data on demographics, health information, caregiver burden, anticipatory grief, and depressive symptoms. We also …

Development And Clinical Implementation Of A Digital Workflow Utilizing 3d-Printed Oral Stents For Patients With Head And Neck Cancer Receiving Radiotherapy, Rance Tino, Millicent A Roach, Gabriela D Fuentes, Anshuman Agrawal, Mohamed Zaid, Dylan J Cooper, Nimit Bajaj, Ruitao Lin, Lianchun Xiao, Lauren L Mayo, Lee R Wiederhold, Shalin J Shah, Molly K Tate, Gregory M Chronowski, Jay P Reddy, Megan Mezera, Justin M Mann, Mark Augspurger, Adegbenga O Otun, Mark S Chambers, Eugene J Koay

Faculty, Staff and Student Publications

Objectives: We describe the development of 3D-printed stents using our digital workflow and their effects on patients enrolled in the lead-in phase of a multi-center, randomized Phase-II trial.

Materials and methods: Digital dental models were created for patients using intraoral scanning. Digital processes were implemented to develop the mouth-opening, tongue-depressing, and tongue-lateralizing stents using stereolithography. Time spent and material 3D-printing costs were measured. Physicians assessed mucositis using the Oral Mucositis Assessment Scale (OMAS) and collected MD Anderson Symptom Inventory (MDASI) reports and adverse events (AEs) from patients at various time points (TPs). OMAS and MDASI results were evaluated using paired …

Influenza C Virus In U.S. Children With Acute Respiratory Infection 2016-2019., Bethany K. Sederdahl, Geoffrey A. Weinberg, Angela P. Campbell, Rangaraj Selvarangan, Jennifer E. Schuster, Joana Y. Lively, Samantha M. Olson, Julie A. Boom, Pedro A. Piedra, Natasha B. Halasa, Laura Stewart, Peter G. Szilagyi, G K Balasubramani, Theresa Sax, Judith M. Martin, Robert W. Hickey, Marian G. Michaels, John V. Williams, New Vaccine Surveillance Network

Manuscripts, Articles, Book Chapters and Other Papers

Influenza C virus (ICV) is an orthomyxovirus related to influenza A and B, yet due to few commercial assays, epidemiologic studies may underestimate incidence of ICV infection and disease. We describe the epidemiology and characteristics of ICV within the New Vaccine Surveillance Network (NVSN), a Centers for Disease Control and Prevention (CDC)-led network that conducts population-based surveillance for pediatric acute respiratory illness (ARI). Nasal or/combined throat swabs were collected from emergency department (ED) or inpatient ARI cases, or healthy controls, between 12/05/2016-10/31/2019 and tested by molecular assays for ICV and other respiratory viruses. Parent surveys and chart review were used …

Substance Use Emergency Department Visits Among Youths With Chronic Conditions During Covid-19., Faith Summersett Williams, Isabella Zaniletti, Abbey R. Masonbrink, Robert Garofalo, Maria Rahmandar, Niranjan S. Karnik, Geri Donenberg, Lisa Kuhns

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Pediatric emergency department (ED) visits for substance use (SU) increased during COVID-19. Better understanding of trends associated with SU ED visits among youths with a chronic medical condition (CMC) is needed to target SU screening, prevention, and intervention efforts in this population.

OBJECTIVE: To describe trends in pediatric SU ED visits before and during COVID-19 among youths in the US with and without CMCs and by race and ethnicity.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, data were obtained from 47 US children's hospital EDs in the Pediatric Health Information System (PHIS) between March 1, 2018, and March …

Technical Pitfalls For Fenestrated-Branched Endovascular Aortic Repair Following Petticoat, Aidin Baghbani-Oskouei, Emanuel R Tenorio, Marina Dias-Neto, Andrea Vacirca, Aleem K Mirza, Naveed Saqib, Bernardo C Mendes, Laura Ocasio, Thanila A Macedo, Gustavo S Oderich

Faculty, Staff and Student Publications

Purpose: The Provisional Extension to Induce Complete Attachment Technique (PETTICOAT) uses a bare-metal stent to scaffold the true lumen in patients with acute or subacute aortic dissections. While it is designed to facilitate remodeling, some patients with chronic post-dissection thoracoabdominal aortic aneurysms (TAAAs) require repair. This study describes the technical pitfalls of fenestrated-branched endovascular aortic repair (FB-EVAR) in patients who underwent prior PETTICOAT repair.

Technique: We report 3 patients with extent II TAAAs who had prior bare-metal dissection stents treated by FB-EVAR. Two patients required maneuvers to reroute the aortic guidewire, which was initially placed in-between stent struts. This was …

Mutational Characteristics And Clinical Outcomes For Lung Adenocarcinoma With Egfr Germline Mutations, Kelsey Pan, Jennifer Owens, Yasir Elamin, Charles Lu, Mark Routbort, Jianjun Zhang, Frank Fossella, Marcelo V Negrao, Mehmet Altan, Jenny Pozadzides, Ferdinandos Skoulidis, Anne Tsao, Tina Cascone, John V Heymach, Edwin Ostrin, Xiuning Le

Faculty, Staff and Student Publications

Introduction: Germline mutations driving lung cancer have been infrequently reported in the literature, with EGFR T790M being a known germline mutation identified in 1% of NSCLCs. Typically, a somatic EGFR mutation is acquired to develop lung adenocarcinoma. Osimertinib has become a standard-of-care treatment for EGFR T790M-positive lung cancer.

Methods: We perform a retrospective analysis through the Lung Cancer Moon Shot GEMINI database at the University of Texas MD Anderson Cancer Center. Of the patients that underwent cell-free DNA analysis, germline mutations were identified by those with high variant allelic fraction approximating 50%, followed by further confirmation on genetic testing.

Results: …

Lower Intensity Therapy With Cladribine/Low Dose Cytarabine/Venetoclax In Older Patients With Acute Myeloid Leukemia Compares Favorably With Intensive Chemotherapy Among Patients Undergoing Allogeneic Stem Cell Transplantation, Jayastu Senapati, Hagop M Kantarjian, Alexandre Bazinet, Patrick Reville, Nicholas J Short, Naval Daver, Gautam Borthakur, Alex Bataller, Elias Jabbour, Courtney Dinardo, Fadi Haddad, Koji Sasaki, Uday Popat, Betul Oran, Amin M Alousi, Sanam Loghavi, Elizabeth Shpall, Guillermo Garcia-Manero, Farhad Ravandi, Tapan M Kadia

Faculty, Staff and Student Publications

Background: Allogeneic stem cell transplantation (SCT) remains the best consolidative modality in most patients with acute myeloid leukemia (AML). Along with factors directly pertaining to SCT, pretransplantation disease control, performance status, and prior treatment-related complications are important factors that affect posttransplantation survival outcomes.

Methods: The authors compared the survival outcomes of patients ≥60 years of age treated on the phase 2 clinical trial of venetoclax (Ven) added to cladribine (CLAD) and low dose cytarabine (LDAC) alternating with azacitidine (CLAD/LDAC/Ven arm) (NCT03586609) who underwent allogeneic SCT in first remission to a retrospective cohort of patients ≥60 years of age …

Drug-Resistant Epilepsy In Tuberous Sclerosis Complex Is Associated With Tsc2 Genotype: More Findings From The Preventing Epilepsy Using Vigatrin (Prevent) Trial, Laura S Farach, Melissa A Richard, Aynara C Wulsin, Elizabeth M Bebin, Darcy A Krueger, Mustafa Sahin, Brenda E Porter, Tarrant O Mcpherson, Jurriaan M Peters, Sarah O'Kelley, Katherine S Taub, Rajsekar Rajaraman, Stephanie C Randle, William M Mcclintock, Mary Kay Koenig, Michael D Frost, Klaus Werner, Danielle A Nolan, Michael Wong, Gary Cutter, Hope Northrup, Kit Sing Au

Faculty, Staff and Student Publications

Background: Children with tuberous sclerosis complex (TSC) are at high risk for drug-resistant epilepsy (DRE). The ability to stratify those at highest risk for DRE is important for counseling and prompt, aggressive management, necessary to optimize neurocognitive outcomes. Using the extensively phenotyped PREVeNT cohort, we aimed to characterize whether the TSC genotype was associated with DRE.

Methods: The study group (N = 70) comprised participants with TSC enrolled at age less than or equal to six months with detailed epilepsy and other phenotypic and genotypic data, prospectively collected as part of the PREVeNT trial. Genotype-phenotype correlations of DRE, time to …

Asxl1/Tet2 Genotype-Based Risk Stratification Outperforms Asxl1 Mutational Impact And Is Independent Of Mutant Variant Allele Fractions In Chronic Myelomonocytic Leukemia, Clifford M Csizmar, Mark Gurney, Rashmi Kanagal-Shamanna, Kelly Chien, Danielle Hammond, Terra L Lasho, Christy M Finke, Christopher Dean, Anuya Natu, Abhishek A Mangaonkar, Aref Al-Kali, Naseema Gangat, Ayalew Tefferi, Hassan Alkhateeb, Guillermo Garcia-Manero, Rami S Komrokji, Najla A Ali, Eric Padron, Guillermo Montalban-Bravo, Mrinal M Patnaik

Faculty, Staff and Student Publications

No abstract provided.

Downregulation Of Uba1 Expression In Myelodysplastic Neoplasm, Yue Wei, Hong Zheng, Ziyi Li, Pamela Pennington Lockyer, Faezeh Darbaniyan, Rashmi Kanagal-Shamanna, Hui Yang, Danielle Hammond, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

No abstract provided.

Congenital Diaphragmatic Hernia And Cleft Lip And Palate: Looking For A Common Genetic Etiology, Petra Nord, Ashley H Ebanks, Petra Peterson, Erik Iwarsson, Matthew T Harting, Carmen Mesas Burgos

Faculty, Staff and Student Publications

Purpose: Congenital diaphragmatic hernia (CDH) and cleft lip and/or palate (CL/P) are inborn closure defects. Genetic factors in and outcomes for patients with both anomalies (CDH+CL/P) remain unclear. We aimed to investigate associated genetic aberrations, prevalence of, and outcomes for, CDH+CL/P.

Methods: Data from Congenital Diaphragmatic Hernia Study Group (CDHSG) registry were collected. CL/P prevalence in CDH patients was determined. Genetic abnormalities and additional malformations in CDH+CL/P were explored. Patient characteristics and outcomes were compared between CDH+CL/P and isolated CDH (CDH-) using Fisher's Exact Test for categorical, and t-test or Mann-Whitney U-test for continuous, data. p < 0.05 was considered statistically significant.

Results: Genetic anomalies in …

Subsyndromes And Symptom Clusters: Multilevel Factor Analysis Of Behavioral And Psychological Symptoms Of Dementia With Intensive Longitudinal Data, Carolyn E Z Pickering, Vicki Winstead, Mustafa Yildiz, Danny Wang, Maria Yefimova, Andrew M Pickering

Faculty, Staff and Student Publications

Introduction: Behavioral and psychological symptoms in dementia (BPSD) are dynamic phenomena with a high amount of intraindividual variability. We applied a multilevel framework to identify subsyndromes (between-person factors) that represent clinically relevant profiles of BPSD and identify symptom clusters (within-person factors) that represent contextually driven daily symptom experiences.

Methods: This study used an intensive longitudinal design in which 68 co-residing family caregivers to persons living with dementia were recruited to proxy report on their care recipient's daily symptom experiences of 23 different BPSD for eight consecutive days (n = 443 diaries). A multilevel exploratory/confirmatory factor analysis was used to account …

Impact Of Race And Ethnicity On Outcomes After Umbilical Cord Blood Transplantation, Karen Ballen, Tao Wang, Naya He, Jennifer M Knight, Sanghee Hong, Haydar Frangoul, Leo F Verdonck, Amir Steinberg, Miguel A Diaz, C Fred Lemaistre, Sherif M Badawy, Jeffrey J Pu, Hasan Hashem, Bipin Savani, Akshay Sharma, Hillard M Lazarus, Muhammad Bilal Abid, Jason Tay, Hemalatha G Rangarajan, Tamila Kindwall-Keller, Cesar O Freytes, Amer Beitinjaneh, Lena E Winestone, Usama Gergis, Nosha Farhadfar, Neel S Bhatt, Raquel M Schears, David Gómez-Almaguer, Mahmoud Aljurf, Vaibhav Agrawal, Yachiyo Kuwatsuka, Sachiko Seo, David I Marks, Leslie Lehmann, William A Wood, Shahrukh Hashmi, Wael Saber

Faculty, Staff and Student Publications

Background: Umbilical cord blood transplant (UCBT) improves access to transplant for patients lacking a fully matched donor. Previous Center for International Blood and Marrow Transplant Research (CIBMTR) showed that Black patients had a lower overall survival (OS) than White patients following single UCBT. The current study draws on a larger modern cohort and compares outcomes among White, Latinx, Black, and Asian patients.

Objective: To compare outcomes by social determinants of health.

Study design: We designed a retrospective study using CIBMTR data. US patients were between ages 1 and 80; 983 received single and 1529 double UCBT as reported to CIBMTR, …

Late Subsequent Leukemia After Childhood Cancer: A Report From The Childhood Cancer Survivor Study (Ccss), Taumoha Ghosh, Geehong Hyun, Rikeenkumar Dhaduk, Miriam Conces, Michael A Arnold, Rebecca M Howell, Tara O Henderson, Aaron Mcdonald, Leslie L Robison, Yutaka Yasui, Kirsten K Ness, Gregory T Armstrong, Joseph P Neglia, Lucie M Turcotte

Faculty, Staff and Student Publications

Background: Subsequent short-latency leukemias are well-described among survivors of childhood cancer. However, late (5-14.9 years from diagnosis, LL) and very late (≥15 years from diagnosis, VLL) subsequent leukemias have not been well studied. We assessed risk factors, prevalence, and outcomes for LL and VLL in the Childhood Cancer Survivor Study cohort.

Methods: Subsequent leukemias, among 25,656 five-year survivors, were self-reported and confirmed by pathology review. Standardized incidence ratios (SIR) and cumulative incidences were calculated, and relative risks (RR) were estimated using Cox regression for exposures.

Results: Seventy-seven survivors developed subsequent leukemia, 49 survivors with LL (median time from diagnosis 7.8 …

Prognostic Scores For Ursodeoxycholic Acid-Treated Patients Predict Graft Loss And Mortality In Recurrent Primary Biliary Cholangitis After Liver Transplantation, Aldo J Montano-Loza, Ellina Lytvyak, Gideon Hirschfield, Bettina E Hansen, Maryam Ebadi, Thierry Berney, Christian Toso, Giulia Magini, Alejandra Villamil, Frederik Nevens, Natalie Van Den Ende, Albert Pares, Pablo Ruiz, Débora Terrabuio, Palak J Trivedi, Nadir Abbas, Maria Francesca Donato, Lei Yu, Charles Landis, Jérôme Dumortier, Jessica Katharine Dyson, Adriaan J Van Der Meer, Rozanne De Veer, Mark Pedersen, Marlyn Mayo, Michael P Manns, Richard Taubert, Theresa Kirchner, Luca S Belli, Chiara Mazzarelli, Guido Stirnimann, Annarosa Floreani, Nora Cazzagon, Francesco Paolo Russo, Patrizia Burra, Udi Zigmound, Inbal Houri, Marco Carbone, Giacomo Mulinacci, Stefano Fagiuoli, Daniel Stephan Pratt, Alan Bonder, Thomas D Schiano, Brandy Haydel, Ansgar Lohse, Christoph Schramm, Darius Rüther, Stefania Casu, Xavier Verhelst, Benedetta Terziroli Beretta-Piccoli, Mercedes Robles, Andrew L Mason, Christophe Corpechot, Global Pbc Study Group

Faculty, Staff and Student Publications

Background & aims: Recurrent primary biliary cholangitis (rPBC) develops in approximately 30% of patients and negatively impacts graft and overall patient survival after liver transplantation (LT). There is a lack of data regarding the response rate to ursodeoxycholic acid (UDCA) in rPBC. We evaluated a large, international, multi-center cohort to assess the performance of PBC scores in predicting the risk of graft and overall survival after LT in patients with rPBC.

Methods: A total of 332 patients with rPBC after LT were evaluated from 28 centers across Europe, North and South America. The median age at the time of rPBC …

Il-22 Resolves Masld Via Enterocyte Stat3 Restoration Of Diet-Perturbed Intestinal Homeostasis, Peng Zhang, Junlai Liu, Allen Lee, Irene Tsaur, Masafumi Ohira, Vivian Duong, Nicholas Vo, Kosuke Watari, Hua Su, Ju Youn Kim, Li Gu, Mandy Zhu, Shabnam Shalapour, Mojgan Hosseini, Gautam Bandyopadhyay, Suling Zeng, Cristina Llorente, Haoqi Nina Zhao, Santosh Lamichhane, Siddharth Mohan, Pieter C Dorrestein, Jerrold M Olefsky, Bernd Schnabl, Pejman Soroosh, Michael Karin

Faculty, Staff and Student Publications

The exponential rise in metabolic dysfunction-associated steatotic liver disease (MASLD) parallels the ever-increasing consumption of energy-dense diets, underscoring the need for effective MASLD-resolving drugs. MASLD pathogenesis is linked to obesity, diabetes, "gut-liver axis" alterations, and defective interleukin-22 (IL-22) signaling. Although barrier-protective IL-22 blunts diet-induced metabolic alterations, inhibits lipid intake, and reverses microbial dysbiosis, obesogenic diets rapidly suppress its production by small intestine-localized innate lymphocytes. This results in STAT3 inhibition in intestinal epithelial cells (IECs) and expansion of the absorptive enterocyte compartment. These MASLD-sustaining aberrations were reversed by administration of recombinant IL-22, which resolved hepatosteatosis, inflammation, fibrosis, and insulin resistance. Exogenous …

The Qiba Profile For Diffusion-Weighted Mri: Apparent Diffusion Coefficient As A Quantitative Imaging Biomarker, Michael A Boss, Dariya Malyarenko, Savannah Partridge, Nancy Obuchowski, Amita Shukla-Dave, Jessica M Winfield, Clifton D Fuller, Kevin Miller, Virendra Mishra, Michael Ohliger, Lisa J Wilmes, Raj Attariwala, Trevor Andrews, Nandita M Desouza, Daniel J Margolis, Thomas L Chenevert

Faculty, Staff and Student Publications

The apparent diffusion coefficient (ADC) provides a quantitative measure of water mobility that can be used to probe alterations in tissue microstructure due to disease or treatment. Establishment of the accepted level of variance in ADC measurements for each clinical application is critical for its successful implementation. The Diffusion-Weighted Imaging Biomarker Committee of the Quantitative Imaging Biomarkers Alliance (QIBA) has recently advanced the ADC Profile from the consensus to clinically feasible stage for the brain, liver, prostate, and breast. This profile distills multiple studies on ADC repeatability and describes detailed procedures to achieve stated performance claims on an observed ADC …

Targeting Multiple Receptor Tyrosine Kinases With Sitravatinib: A Phase 1b Study In Advanced Renal Cell Carcinoma And Castrate-Resistant Prostate Cancer, Shubham Pant, Byoung Chul Cho, Christos E Kyriakopoulos, Alexander Spira, Nizar Tannir, Theresa L Werner, Xiaohong Yan, Saskia Neuteboom, Richard Chao, Sanjay Goel

Faculty, Staff and Student Publications

Sitravatinib (MGCD516) is an oral inhibitor of several closely related oncogenic tyrosine kinase receptors that include VEGFR-2 (vascular endothelial growth factor receptor-2), AXL, and MET (mesenchymal-epithelial transition). The safety and antitumor activity of sitravatinib are reported in patients from two histologic cohorts (anti-angiogenesis-refractory clear cell renal cell carcinoma [RCC] and castrate-resistant prostate cancer [CRPC] with bone metastases) who participated in a Phase 1/1b study. The patients were enrolled using a 3-stage design that was based on observed objective responses. Objective response rate (ORR) was the primary endpoint. Duration of response, progression-free survival (PFS), overall survival (OS), and safety were also …

Extent Of Resection Thresholds In Molecular Subgroups Of Newly Diagnosed Isocitrate Dehydrogenase-Wildtype Glioblastoma, Antonio Dono, Ping Zhu, Takeshi Takayasu, Octavio Arevalo, Roy Riascos, Nitin Tandon, Leomar Y Ballester, Yoshua Esquenazi

Faculty, Staff and Student Publications

Background and objectives: Maximizing the extent of resection (EOR) improves outcomes in glioblastoma (GBM). However, previous GBM studies have not addressed the EOR impact in molecular subgroups beyond IDH1/IDH2 status. In the current article, we evaluate whether EOR confers a benefit in all GBM subtypes or only in particular molecular subgroups.

Methods: A retrospective cohort of newly diagnosed GBM isocitrate dehydrogenase (IDH)-wildtype undergoing resection were prospectively included in a database (n = 138). EOR and residual tumor volume (RTV) were quantified with semiautomated software. Formalin-fixed paraffin-embedded tumor tissues were analyzed by targeted next-generation sequencing. The association between recurrent genomic alterations …

Imageable Radioembolization Microspheres For Treatment Of Unresectable Hepatocellular Carcinoma: Interim Results From A First-In-Human Trial, Robert J Abraham, Aravind Arepally, David Liu, Robert Lewandowski, S Cheenu Kappadath, Amit Verma, David Dobrowski, Andrew Holden

Faculty, Staff and Student Publications

Purpose: To determine 6-month interim safety, effectiveness, and multimodal imageability of imageable glass microsphere yttrium-90 (90Y) radioembolization for unresectable hepatocellular carcinoma (HCC) in a first-in-human trial.

Materials and methods: Imageable microspheres (Eye90 Microspheres; ABK Biomedical, Halifax, Nova Scotia, Canada), a U.S. Food and Drug Administration (FDA) Breakthrough-Designated Device consisting of glass radiopaque 90Y microspheres visible on computed tomography (CT) and single photon emission CT (SPECT), were used to treat 6 subjects with unresectable HCC. Patients underwent selective (≤2 segments) treatment in a prospective open-label pilot trial. Key inclusion criteria included liver-only HCC, performance status ≤1, total lesion diameter ≤9 cm, …