Medicine and Health Sciences Commons^™

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, …

Radiotherapy In The Treatment Of Primary Cutaneous Cd4+ Small/Medium T-Cell Lymphoproliferative Disorder, Susan Y Wu, Ethan P Damron, Jie Xu, Penny Q Fang, Julia Dai, Ranjit Nair, Luis E Malpica Castillo, Luis E Fayad, Carlos A Torres-Cabala, L Jeffrey Medeiros, Francisco Vega, Roberto N Miranda, Madeleine Duvic, Chelsea C Pinnix, Bouthaina S Dabaja, Swaminathan P Iyer, Auris O Huen, Jillian R Gunther

Faculty, Staff and Student Publications

Background: Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (PCSM-LPD) is an increasingly recognized entity with heterogeneous management strategies that may include radiotherapy.

Objective: Our aim was to characterize treatment options for PCSM-LPD, with a focus on the role of radiotherapy.

Methods: This is a retrospective review of 46 patients seen in the Cutaneous Lymphoma Program at the University of Texas MD Anderson Cancer Center, with a clinicopathologic review consistent with PCSM-LPD. All patients were biopsied and underwent observation, topical/intralesional steroids, and/or radiotherapy. Patients were confirmed to have residual disease prior to radiotherapy.

Results: All patients achieved a complete response (CR). …

Healthcare Costs In The United States By Demographic Characteristics And Comorbidity Status, Naomi N Adjei, Allen Haas, Charlotte C Sun, Hui Zhao, Paul G Yeh, Sharon H Giordano, Iakovos Toumazis, Larissa A Meyer

Faculty, Staff and Student Publications

Objectives: Current, real-world healthcare cost information is needed to project future expenditures and inform policy. We estimated the healthcare costs for adults in 2019 in the United States by age, sex, race/ethnicity, geographic region, and comorbidity.

Methods: We aggregated and summarized the healthcare costs in 2021 US dollars using claims data derived from Optum's deidentified Clinformatics® Data Mart Database, which includes inpatient, outpatient, and prescription claims for commercial and Medicare Advantage beneficiaries nationwide.

Results: A total of 9 227 901 adults were included in the analysis. The largest group represented was 71 to 75 years old (13%), female (53%), White …

Respiratory Outcomes Of Infants Born Extremely Preterm In The Necrotizing Enterocolitis Surgery Trial, Sara B Demauro, Erik A Jensen, Scott A Mcdonald, Susan Hintz, Jon Tyson, David K Stevenson, Martin L Blakely

Faculty, Staff and Student Publications

The multicenter Necrotizing Enterocolitis Surgery Trial compared initial peritoneal drainage with laparotomy among infants with extremely low birth weight and surgical necrotizing enterocolitis or intestinal perforation. In this post hoc analysis of trial data, initial drainage was associated with adverse respiratory outcomes, both in hospital and through 2 years corrected age.

Adipose Tissue Deficiency Impairs Transient Lipid Accumulation And Delays Liver Regeneration Following Partial Hepatectomy In Male Seipin Knockout Mice, Qianqian Dong, Ziwei Liu, Yidan Ma, Xin Chen, Xiaowei Wang, Jinye Tang, Kexin Ma, Chenxi Liang, Mengyu Wang, Xiaoqin Wu, Yang Liu, Yaru Zhou, Hongyuan Yang, Mingming Gao

Faculty, Staff and Student Publications

Background: Liver diseases pose significant health challenges, underscoring the importance of understanding liver regeneration mechanisms. Systemic adipose tissue is thought to be a primary source of lipids and energy during this process; however, empirical data on the effects of adipose tissue deficiency are limited. This study investigates the role of adipose tissue in liver regeneration, focusing on transient regeneration-associated steatosis (TRAS) and hepatocyte proliferation using a Seipin knockout mouse model that mimics severe human lipodystrophy. Additionally, the study explores therapeutic strategies through adipose tissue transplantation.

Methods: Male Seipin knockout (Seipin-/-) and wild-type (WT) mice underwent 2/3 partial hepatectomy (PHx). Liver …

Psychiatric Manifestations Of Encephalitis, Paris Bean, Ashley Heck, Ralph Habis, Swathi Sowmitran, Zoe Cartaina, Rajesh Gupta, John Probasco, Rodrigo Hasbun, Arun Venkatesan

Faculty, Staff and Student Publications

Objective: Encephalitis is a serious and potentially life-threatening condition of infectious or autoimmune cause. We aim to characterize the frequency and clinical spectrum of presenting psychiatric symptoms in encephalitis in order to inform earlier recognition and initiation of treatment.

Methods: This was a retrospective study of adult patients who met the 2013 International Encephalitis Consortium (IEC) and/or 2016 Graus criteria between February 2005 and February 2023. The study included two hospital systems in Houston, Texas, and Baltimore, Maryland and included a total of 642 patients. Psychiatric manifestations were grouped into five high-level categories: behavior, psychosis, mood, sleep disturbances, and catatonia. …

A Phase 2 Basket Study Of Talabostat, A Small-Molecule Inhibitor Of Dipeptidyl Peptidases, Administered In Combination With Pembrolizumab In Patients With Advanced Solid Cancers, Jibran Ahmed, Filip Janku, Daniel D Karp, Sarina A Piha-Paul, Apostolia M Tsimberidou, Timothy Anthony Yap, Bettzy Stephen, Yali Yang, Serdar Gurses, Qian Liu, Juhee Song, Funda Meric-Bernstam, Aung Naing

Faculty, Staff and Student Publications

Background: Talabostat, an oral small molecule inhibitor of dipeptidyl peptidases (DPP4 and DPP8/9), has shown synergistic activity with immune checkpoint inhibitors in preclinical studies. This open label, phase 2 basket trial assessed the antitumor activity of combining talabostat and pembrolizumab (anti-programmed death-1 antibody) in advanced solid tumor patients.

Methods: The primary objective was assessment of dose-limiting toxicity (DLT) rates in the first six patients (lead-in stage) and response rate (efficacy stage; included cohort A [checkpoint inhibitor (ICI) naive] and cohort B [ICI pretreated]) for the study treatment using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune RECIST …

Recurrence-Free Survival Prediction For Anal Squamous Cell Carcinoma After Chemoradiotherapy Using Planning Ct-Based Radiomics Model, Shanshan Tang, Kai Wang, David Hein, Gloria Lin, Nina N Sanford, Jing Wang

Faculty, Staff and Student Publications

Objectives: Approximately 30% of non-metastatic anal squamous cell carcinoma (ASCC) patients will experience recurrence after chemoradiotherapy (CRT), and currently available clinical variables are poor predictors of treatment response. We aimed to develop a model leveraging information extracted from radiation pretreatment planning CT to predict recurrence-free survival (RFS) in ASCC patients after CRT.

Methods: Radiomics features were extracted from planning CT images of 96 ASCC patients. Following pre-feature selection, the optimal feature set was selected via step-forward feature selection with a multivariate Cox proportional hazard model. The RFS prediction was generated from a radiomics-clinical combined model based on an optimal feature …

Somatic Copy Number Deletion Of Chromosome 22q In Papillary Thyroid Carcinoma, Olivia W Lee, Danielle M Karyadi, Stephen W Hartley, Weyin Zhou, Mitchell J Machiela, Shahriar A Zamani, Liudmyla Yu Zurnadzhy, John N Weinstein, Young Joo Park, Jeong-Sun Seo, Gerry A Thomas, Tetiana I Bogdanova, Mykola D Tronko, Lindsay M Morton, Stephen J Chanock

Faculty, Staff and Student Publications

Deletion of the long q arm of chromosome 22 (22qDEL) is the most frequently identified recurrent somatic copy number alteration observed in papillary thyroid carcinoma (PTC). Since its role in PTC is not fully understood, we conducted a pooled analysis of genomic characteristics and clinical correlates in 1094 primary tumors from four published PTC genomic studies. The majority of PTC cases with 22qDEL exhibited arm-level loss of heterozygosity (86%); nearly all PTC cases with 22qDEL had losses in 22q12 and 13, which together constitute 70% of the q arm. Our analysis confirmed that 22qDEL occurs more frequently with RAS point …

Exploring Reciprocal Links Between Early Adolescent Coping And Internalizing Symptoms, Caitlyn Mytelka, Sarah C Narendorf, Elizabeth Baumler, Chiara Acquati, Jeff R Temple

Faculty, Staff and Student Publications

Introduction: The rising prevalence of depression and anxiety among adolescents is a public health concern. Early adolescence is a key developmental period to reduce risks for internalizing symptoms through primary prevention programs, yet additional research is needed on modifiable factors, such as coping skills, to target to mitigate risk factors. Therefore, we investigated the reciprocal link between coping style and internalizing symptoms among a racially/ethnically diverse sample of early adolescents (n = 1273) from 12 middle schools over 1 year.

Methods: We leveraged a longitudinal data set of a cluster, randomized trial of a preventive intervention from 12 middle schools …

Cultural Consensus Modeling To Identify Culturally Relevant Reasons For And Against Suicide Among Black Adolescents, Ryan M Hill, Danielle Busby, Jennifer L Brown, Eric Sumlin, Estefania Fernandez, Carla Sharp

Faculty, Staff and Student Publications

Introduction: The development of evidence-based treatments relies on accurate theoretical frameworks sensitive to the lived realities of the populations from which they are derived. Yet, the perspectives of Black youth are vastly underrepresented in extant theories of suicidal behavior. Cultural Consensus Modeling provides an evidence-based approach for developing a culturally informed understanding of suicide risk among Black youth.

Method: Participants were 50 Black adolescents (Mage = 16.20 years; 76.0% male) who completed Phase 1 of a Cultural Consensus Modeling study. Participants freely listed reasons for suicide and reasons for living among similar peer Black youth. Responses were synthesized and coded …

Angiotensin-(1-9) Improves The Cardioprotective Effects Of Del Nido Cardioplegia Against Ischemia/Reperfusion Injury, Evelyn Mendoza-Torres, Gina Sanchez, Wendy Rosales, María Clara Ospino, Luis Antonio Díaz-Ariza, Yuliet Montoya, John Bustamante, Jaime A Riquelme, Mario Chiong, Sergio Lavandero

Faculty, Staff and Student Publications

Del Nido cardioplegia (DNC), a blood-and-crystalloid solution containing high and low concentrations of potassium and calcium, respectively, is used as a single-dose antegrade infusion to induce immediate cardiac arrest in the surgery of patients with cardiovascular diseases requiring extracorporeal circulation. Adding cardioprotective molecules may further reduce the damage-triggered ischemia/reperfusion (I/R) injury. Angiotensin-(1-9) (Ang-(1-9)) and angiotensin-(1-7) (Ang-(1-7)), members of the counter-regulatory renin-angiotensin system, have shown cardioprotective effects in cardiac hypertrophy and I/R models. This study aimed to evaluate the effects of Ang-(1-9) and Ang-(1-7), as adjuvants of the DNC, on cardioprotection and ventricular function in isolated rat hearts subjected to I/R …

Obesity Predisposes Anthracycline-Treated Survivors Of Childhood And Adolescent Cancers To Subclinical Cardiac Dysfunction, Ian A George, Brianna Souder, Amy Berkman, David H Noyd, M Jay Campbell, Piers C A Barker, Michael Roth, Michelle A T Hildebrandt, Kevin C Oeffinger, Andrew W Mccrary, Andrew P Landstrom

Faculty, Staff and Student Publications

Anthracyclines are effective chemotherapeutics used in approximately 60% of pediatric cancer cases but have a well-documented risk of cardiotoxicity. Existing cardiotoxicity risk calculators do not include cardiovascular risk factors present at the time of diagnosis. The goal of this study is to leverage the advanced sensitivity of strain echocardiography to identify pre-existing risk factors for early subclinical cardiac dysfunction among anthracycline-exposed pediatric patients. We identified 115 pediatric patients with cancer who were treated with an anthracycline between 2013 and 2019. Peak longitudinal left ventricular strain was retroactively calculated on 495 surveillance echocardiograms via the TOMTEC AutoSTRAIN software. Cox proportional hazards …

Rezilient3: Randomized Phase Iii Study Of First-Line Zipalertinib Plus Chemotherapy In Patients With Egfr Exon 20 Insertion-Mutated Nsclc, John V Heymach, Helena A Yu, Benjamin Besse, Ying Cheng, Daniel Sw Tan, Li Wei, Volker Wacheck, Makoto Nishio

Faculty, Staff and Student Publications

There remains a significant unmet need for effective and tolerable treatments for patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (

A Phase Ib Trial Of Selinexor In Combination With Immune Checkpoint Blockade In Patients With Advanced Renal Cell Carcinoma, Omar Alhalabi, Mohamed A Gouda, Denái R Milton, Hassan Ahmed Momin, Bulent Yilmaz, Bettzy Stephen, Chinenye Lynette Ejezie, Justin Tyler Moyers, Serdar A Gurses, Jeffrey How, Siqing Fu, Jordi Rodon, David S Hong, Sarina A Piha-Paul, Vivek Subbiah, Ecaterina Elena Dumbrava, Daniel D Karp, Filip Janku, Funda Meric-Bernstam, Nizar M Tannir, Aung Naing

Faculty, Staff and Student Publications

Background: Selinexor (SEL) is a nuclear exportin 1 inhibitor that blocks the transport of nuclear proteins, including tumor suppressors, to the cytoplasm. Preclinical data suggest that the combination of SEL with checkpoint blockade may result in improved response to immunotherapy.

Methods: NCT02419495 was a multiarm phase IB study of SEL in combination with other standard regimens in patients with advanced malignancies. Arm M utilized twice weekly oral SEL and intravenous nivolumab (NIVO). Arm N utilized weekly oral SEL with NIVO plus ipilimumab (IPI). The primary objective of this study was to evaluate the safety of SEL + NIVO and SEL …

Stereotactic Body Radiotherapy Vs Sorafenib Alone In Hepatocellular Carcinoma: The Nrg Oncology/Rtog 1112 Phase 3 Randomized Clinical Trial, Laura A Dawson, Kathryn A Winter, Jennifer J Knox, Andrew X Zhu, Sunil Krishnan, Chandan Guha, Lisa A Kachnic, Michael T Gillin, Theodore S Hong, Timothy D Craig, Terence M Williams, Ali Hosni, Eric Chen, Anne M Noonan, Eugene J Koay, Rishi Sinha, Michael I Lock, Nitin Ohri, Jennifer A Dorth, Guila Delouya, Anand Swaminath, Jennifer Moughan, Christopher H Crane

Faculty, Staff and Student Publications

Importance: Most patients with locally advanced hepatocellular carcinoma (HCC) recur within the liver following systemic therapy.

Objective: To determine whether stereotactic body radiation therapy (SBRT) improves outcomes in patients with locally advanced HCC compared with sorafenib alone.

Design, setting, and participants: This multicenter phase 3 randomized clinical trial randomized patients with HCC 1:1 to sorafenib or SBRT followed by sorafenib, stratified by performance status, liver function, degree of metastases, and macrovascular invasion. Eligible patients had HCC unsuitable for or refractory to standard local-regional therapies and were candidates for first-line systemic therapy. Data were collected from April 2013 to March 2021, …

Best Practices For Delivering Neoadjuvant Therapy In Pancreatic Ductal Adenocarcinoma, Jordan M Cloyd, Angela Sarna, Matthew J Arango, Susan E Bates, Manoop S Bhutani, Mark Bloomston, Vincent Chung, Efrat Dotan, Cristina R Ferrone, Patricia F Gambino, Ajit H Goenka, Karyn A Goodman, William A Hall, Jin He, Melissa E Hogg, Shiva Jayaraman, Avinash Kambadakone, Matthew H G Katz, Alok A Khorana, Andrew H Ko, Eugene J Koay, David A Kooby, Somashekar G Krishna, Liliana K Larsson, Richard T Lee, Anirban Maitra, Nader N Massarweh, Sameh Mikhail, Mahvish Muzaffar, Eileen M O'Reilly, Manisha Palta, Maria Q B Petzel, Philip A Philip, Marsha Reyngold, Daniel Santa Mina, Davendra P S Sohal, Tilak K Sundaresan, Susan Tsai, Kea L Turner, Timothy J Vreeland, Steve Walston, M Kay Washington, Terence M Williams, Jennifer Y Wo, Rebecca A Snyder

Faculty, Staff and Student Publications

Importance: Neoadjuvant therapy (NT) is an increasingly used treatment strategy for patients with localized pancreatic ductal adenocarcinoma (PDAC). Little research has been conducted on cancer care delivery during NT, and the standards for optimal delivery of NT have not been defined.

Objective: To develop consensus best practices for delivering NT to patients with localized PDAC.

Design, setting, and participants: This study used a modified Delphi approach consisting of 2 rounds of voting, and a series of virtual conferences (from October to December 2023) to reach expert consensus on candidate best practice statements generated from a systematic review of the literature …

Undervaluing Nondrug Rewards Or Overvaluing Cocaine? Cocaine Demand Relates To Cocaine Use Severity More Strongly Than Anhedonia In Individuals With Cocaine Use Disorder, Cecilia Nunez, Jin H Yoon, Constanza De Dios, Vincent Dang, Scott D Lane, Jessica N Vincent, Joy M Schmitz, Margaret C Wardle

Faculty, Staff and Student Publications

Cocaine use disorder (CUD) is a major public health issue, and greater cocaine use severity has been associated with worse treatment retention and outcomes. Therefore, greater understanding of processes that influence cocaine use is needed. Both anhedonia (i.e., undervaluation of non-drug rewards) and cocaine demand (i.e., cocaine valuation) are related to cocaine use severity and thematically related to each other at face value, but no studies have directly compared these outcomes to our knowledge. The current study represents a secondary analysis from a two-phase sequential, multiple assignment, randomized trial (SMART) aimed at developing adaptive interventions for CUD. We examined the …

Chemoresistance-Motility Signature Of Molecular Evolution To Chemotherapy In Non-Muscle-Invasive Bladder Cancer And Its Clinical Implications, Mi-So Jeong, Seung-Woo Baek, Gi-Eun Yang, Jeong-Yeon Mun, Jeong Ah Kim, Tae-Nam Kim, Jong-Kil Nam, Yung-Hyun Choi, Ju-Seog Lee, In-Sun Chu, Sun-Hee Leem

Faculty, Staff and Student Publications

Non-muscle-invasive bladder cancer (NMIBC) often recurs and can progress to MIBC due to resistance to treatments like intravesical chemotherapy or Bacillus Calmette-Guérin (BCG). Therefore, we established the Gemcitabine-Resistant Cells (GRCs) to study the molecular evolution under external pressure. A 63-gene Chemoresistance-Motility (CrM) signature was created to identify stage-specific traits of GRCs. This signature was tested on 1846 samples using log-rank tests and Cox regression to evaluate clinical utility. Early and intermediate resistance stages showed increased cell motility and metastatic potential. FAK, PI3K-AKT, and TGFβ pathways were activated first, followed by MAPK signaling. Single-cell analysis and experiments utilizing the CrM signature …

Mayo Genetic Risk Models For Newly Diagnosed Acute Myeloid Leukemia Treated With Venetoclax + Hypomethylating Agent, Naseema Gangat, Azeem Elbeih, Nour Ghosoun, Kristen Mccullough, Fnu Aperna, Isla M Johnson, Maymona Abdelmagid, Aref Al-Kali, Hassan B Alkhateeb, Kebede H Begna, Michelle Elliott, Abhishek Mangaonkar, Aasiya Matin, Antoine N Saliba, Mehrdad Hefazi Torghabeh, Mark R Litzow, William Hogan, Mithun Shah, Mrinal M Patnaik, Animesh Pardanani, Talha Badar, Hemant Murthy, James Foran, Jeanne Palmer, Lisa Sproat, Nandita Khera, Cecilia Arana Yi, Samuel Yates, Abigail Sneider, Emily Dworkin, Anand A Patel, Alexandre Bazinet, Jayastu Senapati, Alex Bataller, Courtney Dinardo, Tapan Kadia, Ayalew Tefferi

Faculty, Staff and Student Publications

Patients with newly diagnosed acute myeloid leukemia (ND-AML) derive variable survival benefit from venetoclax + hypomethylating agent (Ven-HMA) therapy. The primary objective in the current study was to develop genetic risk models that are predictive of survival and are applicable at the time of diagnosis and after establishing treatment response. Among 400 ND-AML patients treated with Ven-HMA at the Mayo Clinic, 247 (62%) achieved complete remission with (CR) or without (CRi) count recovery. Multivariable analysis-derived hazard ratios (HR), including 1.8 for European LeukemiaNet (ELN) adverse karyotype, 4.7 for KMT2Ar, 1.7 for TP53

A Multicenter Open-Label Randomized Phase Ii Study Of Osimertinib With And Without Ramucirumab In Tyrosine Kinase Inhibitor–Naïve Egfr-Mutant Metastatic Non–Small Cell Lung Cancer (Ramose Trial), Xiuning Le, Jyoti D Patel, Elaine Shum, Christina Baik, Rachel E Sanborn, Catherine A Shu, Chul Kim, Mary Jo Fidler, Richard Hall, Yasir Y Elamin, Janet Tu, George Blumenschein, Jianjun Zhang, Don Gibbons, Carl Gay, Nisha A Mohindra, Young Chae, Yanis Boumber, Joshua Sabari, Rafael Santana-Davila, Shane Rogosin, Benjamin Herzberg, Ben Creelan, Bruna Pellini, Tawee Tanvetyanon, Simon Heeke, Mike Hernandez, Jhanelle E Gray, Andreas Saltos, John V Heymach

Faculty, Staff and Student Publications

Purpose: Preclinical studies demonstrated that dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways delay the emergence of resistance to EGFR tyrosine kinase inhibitors (TKIs), and in trials with first-generation EGFR TKIs, the combination of EGFR VEGF pathway inhibitors prolonged progression-free survival (PFS).

Methods: The RAMOSE trial (ClinicalTrials.gov identifier: NCT03909334, HCRN LUN-18-335) is a randomized, open-label multicenter phase II study comparing osimertinib with ramucirumab (arm A) to osimertinib (arm B) for initial treatment of metastatic EGFR-mutant non-small cell lung cancer (NSCLC) with 2:1 random assignment. The primary end point is PFS for …

Chemoresistance-Motility Signature Of Molecular Evolution To Chemotherapy In Non-Muscle-Invasive Bladder Cancer And Its Clinical Implications, Mi-So Jeong, Seung-Woo Baek, Gi-Eun Yang, Jeong-Yeon Mun, Jeong Ah Kim, Tae-Nam Kim, Jong-Kil Nam, Yung-Hyun Choi, Ju-Seog Lee, In-Sun Chu, Sun-Hee Leem

Faculty, Staff and Student Publications

Non-muscle-invasive bladder cancer (NMIBC) often recurs and can progress to MIBC due to resistance to treatments like intravesical chemotherapy or Bacillus Calmette-Guérin (BCG). Therefore, we established the Gemcitabine-Resistant Cells (GRCs) to study the molecular evolution under external pressure. A 63-gene Chemoresistance-Motility (CrM) signature was created to identify stage-specific traits of GRCs. This signature was tested on 1846 samples using log-rank tests and Cox regression to evaluate clinical utility. Early and intermediate resistance stages showed increased cell motility and metastatic potential. FAK, PI3K-AKT, and TGFβ pathways were activated first, followed by MAPK signaling. Single-cell analysis and experiments utilizing the CrM signature …

Outcomes Of Patients With Treated Secondary Acute Myeloid Leukemia: A High-Risk Subtype That Warrants An Independent Prognostic Designation, Jayastu Senapati, Hagop M Kantarjian, Fadi G Haddad, Nicholas J Short, Gautam Borthakur, Rashmi Kanagal-Shamanna, Guilin Tang, Elias Jabbour, Courtney D Dinardo, Naval Daver, Guillermo Montalban-Bravo, Vishrut Shah, Amin Alousi, Elizabeth Shpall, Uday Popat, Guillermo Garcia-Manero, Farhad Ravandi, Tapan M Kadia

Faculty, Staff and Student Publications

Patients who develop acute myeloid leukemia (AML) after having received treatment for myelodysplastic syndrome (MDS) or related conditions have particularly poor outcomes. This study analyzed adult patients with newly diagnosed AML who previously had MDS, chronic myelomonocytic leukemia (CMML), or MDS/myeloproliferative neoplasm (MPN) overlap syndrome, and who had received hypomethylating agents, chemotherapy, and/or allogeneic stem cell transplantation (HSCT) for these antecedent disorders. From January 2012 to August 2023, we included 673 patients with a median age of 70 years (range, 19-94); 536 (80%) had transformed from MDS, and the remainder from CMML or MDS-MPN. Additionally, 149 patients (22%) had prior …

A Randomized, Double-Blind, Placebo-Controlled Trial Of Daxibotulinumtoxina For Injection For The Treatment Of Upper Limb Spasticity In Adults After Stroke Or Traumatic Brain Injury, Atul T Patel, Michael C Munin, Ziyad Ayyoub, Gerard E Francisco, Rashid Kazerooni, Todd M Gross

Faculty, Staff and Student Publications

Background: Intramuscular injection of botulinum toxin type A is a first-line pharmacotherapy for adults with upper limb spasticity (ULS). However, reemergence of symptoms within 12 weeks of treatment is common and longer-lasting treatments are needed.

Objective: To evaluate the efficacy and safety of three doses of DaxibotulinumtoxinA for Injection (DAXI) for treatment of ULS in adults with stroke or traumatic brain injury.

Intervention: Intramuscular injections of placebo (N = 24), DAXI 250 U (N = 22), DAXI 375 U (N = 19), or DAXI 500 U (N = 18) to the suprahypertonic muscle (SMG) and other muscle groups.

Design: Randomized, …

Frailty And Sleep In Adult Survivors Of Childhood Cancer: A Childhood Cancer Survivor Study Report, Lauren C Daniel, Margaret M Lubas, Huiqi Wang, Mariana Szklo-Coxe, Kirsten K Ness, Annalynn M Williams, Daniel A Mulrooney, Rebecca Howell, Wendy Leisenring, Yutaka Yasui, Leslie L Robison, Gregory T Armstrong, Eric J Chow, Kevin R Krull, Tara M Brinkman

Faculty, Staff and Student Publications

Background: Young adult survivors of childhood cancer exhibit rates of frailty similar to adults several decades older without a cancer history. Frailty has been associated with sleep disturbances in non-cancer populations, but the relationship has not been examined in childhood cancer survivors who are known to exhibit elevated rates of sleep problems.

Aims: Examine associations between frailty and poor sleep quality in long-term survivors of childhood cancer.

Methods: This study utilized data from 9044 participants (> 5 years from diagnosis, Mage = 40.8 years [SD = 9.5]) in the Childhood Cancer Survivor Study. Survivors' frailty status, chronic health conditions (CHC), …

Mutational And Co-Mutational Landscape Of Early Onset Colorectal Cancer, Jumanah Yousef Alshenaifi, Guglielmo Vetere, Giulia Maddalena, Mahmoud Yousef, Michael G White, John Paul Shen, Eduardo Vilar, Christine Parseghian, Arvind Dasari, Van Karlyle Morris, Ryan Huey, Michael J Overman, Robert Wolff, Kanwal P Raghav, Jason Willis, Kristin Alfaro, Andy Futreal, Y Nancy You, Scott Kopetz

Faculty, Staff and Student Publications

Introduction: Colorectal cancer (CRC) incidence and mortality before 50 have been rising alarmingly in the recent decades.

Methods: Using a cohort of 10,000 patients, this study investigates the clinical, mutational, and co-mutational features of CRC in early-onset (EOCRC, < 50 years) compared to late-onset (LOCRC, ≥ 50 years).

Results: EOCRC was associated with a higher prevalence of Asian and Hispanic patients, rectal or left-sided tumors (72% vs. 59%), and advanced-stage disease. Molecular analyses revealed differences in mutation patterns, with EOCRC having higher frequencies of TP53 (74% vs. 68%, p < 0.01) and SMAD4 (17% vs. 14%, p = 0.015), while BRAF (5% vs. 11%, p < 0.001) and NOTCH1 (2.7% vs. 4.1%, p = 0.01) mutations …

Refining Diagnostic Subtypes Of Peripheral T-Cell Lymphoma Using A Multiparameter Approach, Catalina Amador, Dennis D Weisenburger, Ana Gomez, Alyssa Bouska, Ahmad Alshomrani, Sunandini Sharma, Ab Rauf Shah, Timothy C Greiner, Francisco Vega, Andreas Rosenwald, German Ott, Andrew L Feldman, Elaine S Jaffe, Neval Ozkaya, Sarah L Ondrejka, James R Cook, Philipp W Raess, Kerry J Savage, Graham W Slack, Joo Y Song, David W Scott, Elias Campo, Lisa M Rimsza, Joseph D Khoury, Louis M Staudt, Wing C Chan, Javeed Iqbal

Faculty, Staff and Student Publications

Peripheral T-cell lymphoma (PTCL) is a heterogeneous category, and many cases are unclassifiable and designated as PTCL-not otherwise specified (PTCL-NOS). Gene expression profiling (GEP) has delineated two prognostic subtypes within PTCL-NOS, PTCL-TBX21, and PTCL-GATA3, characterized by distinctive transcriptomes and a different prognosis. To further evaluate the pathologic features of these subgroups, 101 PTCL cases that did not meet specific criteria for well-defined T-cell lymphoma entities underwent detailed pathologic, immunophenotypic (including TFH biomarkers) and GEP analyses, separating them into PTCL-NOS (n=63) and PTCL-TFH (a.k.a. nodal PTCL-TFH, NOS, and TFH lymphoma, NOS) (n=38). PTCL-NOS cases were further categorized into PTCL-GATA3 (n=22; 34%) …

Forearm Versus Upper Arm Location Of Arteriovenous Access Used At Hemodialysis Initiation: Temporal Trends And Racial Disparities, Melandrea L Worsley, Jingbo Niu, Kevin F Erickson, Neal R Barshes, Wolfgang C Winkelmayer, L Parker Gregg

Faculty, Staff and Students Publications

Rationale & objective: Race and ethnicity differences exist in the type of arteriovenous access (AVA, including fistulas and grafts) used at hemodialysis (HD) initiation. The preferred anatomic location for the creation of an initial HD AVA is typically in the forearm We evaluated race and ethnicity differences in the use of an AVA in the forearm location at HD initiation.

Study design: Retrospective cohort study.

Setting & participants: Using records from DaVita Kidney Care linked to the US Renal Data System (USRDS), we evaluated patients aged≥16 years who initiated in-center HD with an AVA between 2006 and 2019.

Predictor: Race …

Qm107, A Novel Cd148 (Rtp Type J) Activating Peptide Therapy For Treating Neovascular Age-Related Macular Degeneration, Samantha Arokiasamy, Michaela J M Balderstone, Faheem Shaik, Enrico Cristante, Thomas C Moseley, Akshay Madoo, Matteo Rizzi, James W Bainbridge, Konstantin Tsoyi, Ivan O Rosas, James R Whiteford, Giulia De Rossi

Faculty, Staff and Students Publications

Background and purpose: Angiogenesis is a pathological component of neovascular age-related macular degeneration. Current therapies, although successful, are prone to high levels of patient non-response and a loss of efficacy over time, indicating the need to explore other therapeutic avenues. We have shown that an interaction between syndecan-2 and the tyrosine phosphatase receptor CD148 (RTP Type J) results in the ablation of angiogenesis. Here we exploit this pathway to develop a peptide activator of CD148 as a therapy for neovascular age-related macular degeneration.

Experimental approach: We tested a peptide (QM107) derived from syndecan-2 in a variety of angiogenesis models and …

Mid-Life Anti-Inflammatory Metabolites Are Inversely Associated With Long-Term Cardiovascular Disease Events, Anum Saeed, Chris Mckennan, Jiaxuan Duan, Yueh-Ning Yang, Kevin E Kip, David Finegold, Michael Vu, Justin Swanson, Oscar L Lopez, Ann Cohen, Mark Mapstone, Bing Yu, Christie M Ballantyne, Steven E Reis

Faculty, Staff and Student Publications

BACKGROUND: Preclinical data have shown that low levels of metabolites with anti-inflammatory properties may impact metabolic disease processes. However, the association between mid-life levels of such metabolites and long-term ASCVD risk is not known.

METHODS: We characterised the plasma metabolomic profile (1228 metabolites) of 1852 participants (58.1 ± 7.5 years old, 69.6% female, 43.6% self-identified as Black) enrolled in the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study. Logistic regression was used to assess the impact of metabolite levels on ASCVD risk (nonfatal MI, revascularisation, and cardiac mortality). We additionally explored the effect of genetic variants neighbouring ASCVD-related genes …