Biomedical Informatics Commons^™

Association Of Systemic Inflammation And Long-Term Dysfunction In Covid-19 Patients: A Prospective Cohort, Felipe Dal-Pizzol, Bruno Kluwe-Schiavon, Henrique Ritter Dal-Pizzol, Gabriele Da Silveira Prestes, Diogo Dominguini, Carolina Saibro Girardi, Lucas Santos, José Cláudio Fonseca Moreira, Daniel Pens Gelain, Roger Walz, Tatiana Barichello, Cristiane Ritter

Faculty, Staff and Student Publications

COVID-19 has significant long-term impacts, including a chronic syndrome known as long-COVID, characterized by persistent symptoms post-recovery. The inflammatory response during acute infection is hypothesized to influence long-term outcomes. This study aimed to identify inflammatory biomarkers predictive of functional outcomes one year after hospital discharge. A prospective cohort study was conducted with 213 COVID-19 patients admitted to ICUs in Southern Brazil between June and November 2020. After exclusions and follow-ups, 109 patients were evaluated for one-year post-discharge. Plasma levels of Th1 (TNF-α, INF-γ, IL-12), Th2 (IL-4, IL-5, IL-6, IL-10, IL-13), and Th17 (IL-17, IL-22) cytokines were measured. Functional outcomes in …

Immunogenomic Determinants Of Exceptional Response To Immune Checkpoint Inhibition In Renal Cell Carcinoma, Tejas Jammihal, Renee Maria Saliby, Chris Labaki, Hanna Soulati, Juan Gallegos, Arnau Peris, Dustin Mccurry, Chunlei Yu, Valisha Shah, Deepak Poduval, Talal El Zarif, Nourhan El Ahmar, Yasmin Nabil Laimon, Marc Eid, Aseman Bagheri Sheshdeh, Katherine M Krajewski, Florian A Büttner, Matthias Schwab, Daniel Heng, Rafael C Casellas, Kunal Rai, Niki M Zacharias Millward, Pavlos Msaouel, Jose Karam, Sabina Signoretti, Eliezer Van Allen, Toni K Choueiri, David A Braun, Sachet A Shukla

Faculty, Staff and Student Publications

Immune checkpoint inhibitors can lead to 'exceptional', durable responses in a subset of persons. However, the molecular basis of exceptional response (ER) to immunotherapy in metastatic clear cell renal cell carcinoma (mccRCC) has not been well characterized. Here we analyzed pretherapy genomic and transcriptomic data in treatment-naive persons with mccRCC treated with standard-of-care immunotherapies: (1) combination of programmed cell death protein and ligand 1 (PD1/PDL1) and cytotoxic T lymphocyte-associated protein 4 inhibitors (IO/IO) or (2) combination of PD1/PDL1 and vascular endothelial growth factor (VEGF) receptor inhibitors (IO/VEGF). In the IO/IO cohort, clonal neoantigen load was significantly higher in persons with …

Community Outreach, Engagement, And Mentoring Program For Underrepresented Scholars In Cancer Health Disparities, Lorna H Mcneill, Cassandra L Harris, Terrence R Adams, Berta R Salazar, Crystal L Roberson, Leonetta B Thompson, Kamisha H Escoto, Kayce D Solari Williams, Shine Chang, Tzuan A Chen, Birnur Buzcu-Guven, Lorraine R Reitzel

Faculty, Staff and Student Publications

Objective:

Racial/ethnic minorities and women are affected by cancer and cancer risk factors at higher rates; however, they are largely underrepresented in scientific professions focused on health disparities. One way to reduce disparities is to increase diversity within the workforce by planning training activities for minority scholars, paying close attention to community outreach. This paper describes the outcomes of a robust community outreach plan engaging communities in education, research, and clinical trials to increase the number of underrepresented student scholars in cancer disparities research through research training, mentorship, and service-learning activities provided within local organizations.

Methods:

The program provided two …

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 …

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 …

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 …

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 …

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%) …

Respiratory Syncytial Virus Disease Burden And Nirsevimab Effectiveness In Young Children From 2023-2024, Heidi L Moline, Ariana P Toepfer, Ayzsa Tannis, Geoffrey A Weinberg, Mary A Staat, Natasha B Halasa, Julie A Boom, Eileen J Klein, John V Williams, Jennifer E Schuster, Leah Goldstein, Erin R Mckeever, Casey Kalman, Clinton Paden, Lydia Atherton, Megha Aggarwal, Pavitra Roychoudhury, Pedro A Piedra, Leila C Sahni, Laura S Stewart, Rangaraj Selvarangan, Marian G Michaels, Elizabeth P Schlaudecker, Peter G Szilagyi, Janet A Englund, Benjamin R Clopper, Natalie J Thornburg, Gordana Derado, Meredith L Mcmorrow, Fatimah S Dawood, New Vaccine Surveillance Network Collaborators

Faculty, Staff and Students Publications

Importance: During the 2023-2024 respiratory syncytial virus (RSV) season in the United States, 2 new RSV prevention products were recommended to protect infants in their first RSV season: nirsevimab and Pfizer's maternal RSV vaccine. Postlicensure studies are needed to assess prevention product impact and effectiveness.

Objective: To compare the epidemiology and disease burden of medically attended RSV-associated acute respiratory illness (ARI) among children younger than 5 years during the 2023-2024 RSV season with 3 prepandemic RSV seasons (2017-2020), estimate nirsevimab effectiveness against medically attended RSV-associated ARI, and compare nirsevimab binding site mutations among circulating RSV in infants with and without …

Association Of Serum Endocannabinoid Levels With Pancreatitis And Pancreatitis-Related Pain, Marc T Goodman, Christina Lombardi, Alexa Torrens, Catherine Bresee, Jami L Saloman, Liang Li, Yunlong Yang, William E Fisher, Evan L Fogel, Christopher E Forsmark, Darwin L Conwell, Phil A Hart, Walter G Park, Mark Topazian, Santhi S Vege, Stephen K Van Den Eeden, Melena D Bellin, Dana K Andersen, Jose Serrano, Dhiraj Yadav, Stephen J Pandol, Daniele Piomelli

Faculty, Staff and Student Publications

No abstract provided.

Emapalumab Treatment In Patients With Rheumatologic Disease-Associated Hemophagocytic Lymphohistiocytosis In The United States: A Retrospective Medical Chart Review Study, Shanmuganathan Chandrakasan, Carl E Allen, Deepika Bhatla, John Carter, May Chien, Robert Cooper, Lauren Draper, Olive S Eckstein, Rabi Hanna, J Allyson Hays, Michelle L Hermiston, Ashley P Hinson, Patricia M Hobday, Michael S Isakoff, Michael B Jordan, Jennifer W Leiding, Renee Modica, Taizo A Nakano, Abiola Oladapo, Sachit A Patel, Priti Pednekar, Mona Riskalla, Susmita N Sarangi, Prakash Satwani, Anand Tandra, Kelly J Walkovich, John D Yee, Adi Zoref-Lorenz, Edward M Behrens

Faculty, Staff and Students Publications

Objective: Rheumatologic disease-associated hemophagocytic lymphohistiocytosis (HLH), a rare, life-threatening, systemic hyperinflammatory syndrome, occurs as a complication of underlying rheumatologic disease. Real-world evidence is lacking on emapalumab, a fully human monoclonal antibody that neutralizes the proinflammatory cytokine interferon-γ, approved for treating patients with primary HLH.

Methods: REAL-HLH, a retrospective medical chart review study conducted across 33 US hospitals, assessed real-world treatment patterns and outcomes in patients with HLH treated with one or more dose of emapalumab between November 20, 2018, and October 31, 2021. Data are presented for the subset of patients with rheumatologic disease-associated HLH.

Results: Fifteen of 105 patients …

Overcoming Cd226-Related Immune Evasion In Acute Myeloid Leukemia With Cd38 Car-Engineered Nk Cells, Luciana Melo Garcia, Achintyan Gangadharan, Pinaki Banerjee, Ye Li, Andy G X Zeng, Hind Rafei, Paul Lin, Bijender Kumar, Sunil Acharya, May Daher, Luis Muniz-Feliciano, Gary M Deyter, Gabriel Dominguez, Jeong Min Park, Francia Reyes Silva, Ana Karen Nunez Cortes, Rafet Basar, Nadima Uprety, Mayra Shanley, Mecit Kaplan, Enli Liu, Elizabeth J Shpall, Katayoun Rezvani

Faculty, Staff and Student Publications

CD226 plays a vital role in natural killer (NK) cell cytotoxicity, interacting with its ligands CD112 and CD155 to initiate immune synapse formation, primarily through leukocyte function-associated-1 (LFA-1). Our study examined the role of CD226 in NK cell surveillance of acute myeloid leukemia (AML). NK cells in patients with AML had lower expression of CD226. CRISPR-Cas9 deletion of CD226 led to reduced LFA-1 recruitment, poor synapse formation, and decreased NK cell anti-leukemic activity. Engineering NK cells to express a chimeric antigen receptor targeting the AML antigen CD38 (CAR38) could overcome the need for CD226 to establish strong immune synapses. LFA-1 …

Urine Proteomics Defines An Immune Checkpoint-Associated Nephritis Signature, James P Long, Shailbala Singh, Yanlan Dong, Cassian Yee, Jamie S Lin

Faculty, Staff and Student Publications

Immune checkpoint inhibitor (ICI) therapy is a cornerstone treatment for many cancers, but it can induce severe immunotoxicity, including acute interstitial nephritis (AIN). Currently, kidney biopsy is required to differentiate ICI-AIN from other causes of acute kidney injury (AKI). However, this invasive approach can lead to morbidity, delayed glucocorticoid treatment for patients with AIN, and unnecessarily prolonged suspension of ICI therapy in non-AIN patients. Delayed or incorrect diagnosis of ICI-AIN is particularly detrimental, as over 50% of patients are at risk of permanent renal damage. Thus, there is an urgent need for non-invasive biomarkers that can rapidly and accurately distinguish …

Joint Fluid Multi-Omics Improves Diagnostic Confidence During Evaluation Of Children With Presumed Septic Arthritis, Yolanda Peña-López, Naureen G Tareen, Bo Zhang, Indu Raman, Carlos A Arana, Chengsong Zhu, Yang Liu, Pratibha Selvakumar, Nicolai S C Van Oers, Simrat Morris, Lora V Hooper, Lawson A B Copley, Prithvi Raj

Faculty, Staff and Student Publications

Background: An accurate diagnosis of septic versus reactive or autoimmune arthritis remains clinically challenging. A multi-omics strategy comprising metagenomic and proteomic technologies were undertaken for children diagnosed with presumed septic arthritis to advance clinical diagnoses and care for affected individuals.

Methods: Twelve children with suspected septic arthritis were prospectively enrolled to compare standard of care tests with a rapid multi-omics approach. The multi-omics combined bacterial 16S rRNA metagenomics, single cell transcriptomics, and proteomics on knee joint fluid specimens. The diagnostic value of the multi-omics was ascertained relative to standard of care culture and PCR-negative results.

Results: Ten children with suspected …