Medicine and Health Sciences Commons^™

Identification Of A Single-Dose, Low-Flip-Angle-Based Cbv Threshold For Fractional Tumor Burden Mapping In Recurrent Glioblastoma, Aliya Anil, Ashley M Stokes, John P Karis, Laura C Bell, Jennifer Eschbacher, Kristofer Jennings, Melissa A Prah, Leland S Hu, Jerrold L Boxerman, Kathleen M Schmainda, C Chad Quarles

Faculty, Staff and Student Publications

Background and purpose: DSC-MR imaging can be used to generate fractional tumor burden (FTB) maps via application of relative CBV thresholds to spatially differentiate glioblastoma recurrence from posttreatment radiation effects (PTRE). Image-localized histopathology was previously used to validate FTB maps derived from a reference DSC-MR imaging protocol by using preload, a moderate flip angle (MFA, 60°), and postprocessing leakage correction. Recently, a DSC-MR imaging protocol with a low flip angle (LFA, 30°) with no preload was shown to provide leakage-corrected relative CBV (rCBV) equivalent to the reference protocol. This study aimed to identify the rCBV thresholds for the LFA protocol …

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 …

Pre-Diagnosis Tea And Coffee Consumption And Survival After A Diagnosis Of Ovarian Cancer: Results From The Ovarian Cancer Association Consortium, Christina M Nagle, Torukiri I Ibiebele, Elisa V Bandera, Daniel Cramer, Jennifer A Doherty, Graham G Giles, Marc T Goodman, Gillian E Hanley, Holly R Harris, Allan Jensen, Susanne K Kjaer, Alice W Lee, Roger L Milne, Bo Qin, Jean Richardson, Naoko Sasamoto, Weiva Sieh, Kathryn L Terry, Linda Titus, Britton Trabert, Nicolas Wentzensen, Anna H Wu, Andrew Berchuck, Malcolm Pike, Celeste Leigh Pearce, Penelope M Webb

Faculty, Staff and Student Publications

BACKGROUND: Tea and coffee are the most frequently consumed beverages in the world. Green tea in particular contains compounds with potential anti-cancer effects, but its association with survival after ovarian cancer is uncertain.

METHODS: We investigated the associations between tea and coffee consumption before diagnosis and survival using data from 10 studies in the Ovarian Cancer Association Consortium. Data on tea (green, black, herbal), coffee and caffeine intake were available for up to 5724 women. We used Cox proportional hazards regression to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI).

RESULTS: Compared with women who did not drink …

Dcis Knowledge Of Women Choosing Between Active Surveillance And Surgery For Low-Risk Dcis, E G Engelhardt, R S J M Schmitz, M A Gerritsma, C M T Sondermeijer, E Verschuur, J H E Houtzager, R Griffioen, N Bijker, R M Mann, V Retèl, F H Van Duijnhoven, J Wesseling, E M A Bleiker

Faculty, Staff and Student Publications

BACKGROUND: Ductal carcinoma in situ (DCIS) can progress to invasive breast cancer (IBC), but often never will. As we cannot predict accurately which DCIS-lesions will or will not progress to IBC, almost all women with DCIS undergo breast-conserving surgery supplemented with radiotherapy, or even mastectomy. In some countries, endocrine treatment is prescribed as well. This implies many women with non-progressive DCIS undergo overtreatment. To reduce this, the LORD patient preference trial (LORD-PPT) tests whether mammographic active surveillance (AS) is safe by giving women with low-risk DCIS a choice between treatment and AS. For this, sufficient knowledge about DCIS is crucial. …

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 …

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 …

Outcomes In Solid Organ Transplant Recipients Receiving Organs From A Donor With Fusarium Solani Species Complex Meningitis, Isabel S Griffin, Dallas J Smith, Pallavi Annambhotla, Jeremy A W Gold, Luis Ostrosky-Zeichner, Carol A Kauffman, Lalitha Gade, Anastasia Litvintseva, Daniel Zp Friedman, Angie G Nishio Lucar, Tarina C Parpia, Joshua Lieberman, Janet Bujan, Julie Corkrean, Mukul K Divatia, Kevin Grimes, Jiejian Lin, Constance Mobley, Mary R Schwartz, Bashar Hannawi, Anne Malilay, Anne O'Boye, Jeffrey Lysne, Mrinalini Venkata Subramani, Hayley Heckmann, Venice Servellita, Charles Chiu, Sridhar V Basavaraju

Faculty, Staff and Student Publications

Background: Five organs (heart, right lung, liver, right, and left kidneys) from a deceased patient were transplanted into five recipients in four US states; the deceased patient was identified as part of a healthcare-associated fungal meningitis outbreak among patients who underwent epidural anesthesia in Matamoros, Mexico.

Methods: After transplant surgeries occurred, Fusarium solani species complex, a fungal pathogen with a high case-mortality rate, was identified in cerebrospinal fluid from the organ donor by metagenomic next-generation sequencing (mNGS) and fungal-specific polymerase chain reaction and in plasma by mNGS.

Results: Four of five transplant recipients received recommended voriconazole prophylaxis; four were monitored …

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 …

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.

Percutaneous Sacral Screw Fixation Alone Sufficient For Mildly Displaced U-Type Sacral Fractures With Preserved Osseous Fixation Pathways, Augustine M Saiz, Patrick J Kellam, Adeet Amin, Zachary Arambula, Abhi Rashiwala, Joshua L Gary, Stephen J Warner, Milton Routt, Jonathan G Eastman

Faculty, Staff and Student Publications

Purpose: To describe U-type sacral fracture characteristics amenable to percutaneous sacral screw fixation.

Methods: U-type sacral fractures were identified from a trauma registry at a level 1 trauma center from 2014 to 2020. Patient demographics, injury mechanism, fracture characteristics, and fixation construct were retrospectively retrieved. Associations between fracture pattern and surgical fixation were identified.

Results: 82 U-type sacral fractures were reviewed. Six treated with lumbopelvic fixation (LPF) and 76 were treated with percutaneous sacral screws (PSS) alone. Patients receiving LBF had greater sacral fracture displacement in coronal, sagittal, and axial planes compared to patients receiving PSS alone (P < 0.05), negating osseous fixation pathways. All patients went onto sacral union and there were no implant failures or unplanned reoperations for either group.

Conclusion: If …

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, …

The Toxicology Investigators Consortium 2023 Annual Report, Adrienne Hughes, Alexandra Amaducci, Sharan L Campleman, Shao Li, Mari Costantini, Meghan B Spyres, Hannah Spungen, Jessica Kent, Alyssa Falise, Rachel Culbreth, Paul M Wax, Jeffery Brent, Kim Aldy, Toxicology Investigators Consortium Study Group

Faculty, Staff and Student Publications

Since 2010, the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC) has maintained the ToxIC Core Registry, a national case registry of in-hospital and clinic patient consultations submitted by medical toxicology physicians. Deidentified patient data entered into the registry includes patient demographics, reason for medical toxicology evaluation, exposure agents, clinical signs and symptoms, treatments and antidotes administered, and mortality. This fourteenth annual report provides data from 7392 patients entered into the Core Registry in 2023 by 36 participating sites comprising 61 distinct healthcare facilities, bringing the total case count to 102331 between 2010 and 2023. Ethanol was the …

Diffusion Tensor Imaging For Characterizing Changes In Triple-Negative Breast Cancer During Neoadjuvant Systemic Therapy, Benjamin C Musall, David E Rauch, Rania M M Mohamed, Bikash Panthi, Medine Boge, Rosalind P Candelaria, Huiqin Chen, Mary S Guirguis, Kelly K Hunt, Lei Huo, Ken-Pin Hwang, Anil Korkut, Jennifer K Litton, Tanya W Moseley, Sanaz Pashapoor, Miral M Patel, Brandy J Reed, Marion E Scoggins, Jong Bum Son, Debu Tripathy, Vicente Valero, Peng Wei, Jason B White, Gary J Whitman, Zhan Xu, Wei T Yang, Clinton Yam, Beatriz E Adrada, Jingfei Ma

Faculty, Staff and Student Publications

Background: Assessment of treatment response in triple-negative breast cancer (TNBC) may guide individualized care for improved patient outcomes. Diffusion tensor imaging (DTI) measures tissue anisotropy and could be useful for characterizing changes in the tumors and adjacent fibroglandular tissue (FGT) of TNBC patients undergoing neoadjuvant systemic treatment (NAST).

Purpose: To evaluate the potential of DTI parameters for prediction of treatment response in TNBC patients undergoing NAST.

Study type: Prospective.

Population: Eighty-six women (average age: 51 ± 11 years) with biopsy-proven clinical stage I-III TNBC who underwent NAST followed by definitive surgery. 47% of patients (40/86) had pathologic complete response (pCR). …

Menin Inhibitors In Pediatric Acute Leukemia: A Comprehensive Review And Recommendations To Accelerate Progress In Collaboration With Adult Leukemia And The International Community, Branko Cuglievan, Hagop Kantarjian, Jeffrey E Rubnitz, Todd M Cooper, C Michel Zwaan, Jessica A Pollard, Courtney D Dinardo, Tapan M Kadia, Erin Guest, Nicholas J Short, David Mccall, Naval Daver, Cesar Nunez, Fadi G Haddad, Miriam Garcia, Kapil N Bhalla, Abhishek Maiti, Samanta Catueno, Warren Fiskus, Bing Z Carter, Amber Gibson, Michael Roth, Sajad Khazal, Priti Tewari, Hussein A Abbas, Wallace Bourgeois, Michael Andreeff, Neerav N Shukla, Danh D Truong, Jeremy Connors, Joseph A Ludwig, Janine Stutterheim, Elisabeth Salzer, Kristian L Juul-Dam, Koji Sasaki, Kris M Mahadeo, Sarah K Tasian, Gautam Borthakur, Samantha Dickson, Nitin Jain, Elias Jabbour, Soheil Meshinchi, Guillermo Garcia-Manero, Farhad Ravandi, Eytan M Stein, E Anders Kolb, Ghayas C Issa

Faculty, Staff and Student Publications

Aberrant expression of HOX and MEIS1 family genes, as seen in KMT2A-rearranged, NUP98-rearranged, or NPM1-mutated leukemias leads to arrested differentiation and leukemia development. HOX family genes are essential gatekeepers of physiologic hematopoiesis, and their expression is regulated by the interaction between KMT2A and menin. Menin inhibitors block this interaction, downregulate the abnormal expression of MEIS1 and other transcription factors and thereby release the differentiation block. Menin inhibitors show significant clinical efficacy against KMT2A-rearranged and NPM1-mutated acute leukemias, with promising potential to address unmet needs in various pediatric leukemia subtypes. In this collaborative initiative, pediatric and adult hematologists/oncologists, and stem cell …

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, …

Columbia-1: A Randomised Study Of Durvalumab Plus Oleclumab In Combination With Chemotherapy And Bevacizumab In Metastatic Microsatellite-Stable Colorectal Cancer, Neil H Segal, Jeanne Tie, Scott Kopetz, Michel Ducreux, Eric Chen, Rodrigo Dienstmann, Antoine Hollebecque, Matthew J Reilley, Elena Elez, Jan Cosaert, Jason Cain, Yee Soo-Hoo, Nicola Hewson, Zachary A Cooper, Rakesh Kumar, Josep Tabernero

Faculty, Staff and Student Publications

Background: To determine whether the addition of durvalumab (anti-PD-L1) and oleclumab (anti-CD73) to standard-of-care treatment (FOLFOX and bevacizumab) enhances the anti-tumour effect in patients with metastatic colorectal cancer (mCRC).

Methods: COLUMBIA-1 (NCT04068610) was a Phase Ib (feasibility; Part 1)/Phase II (randomised; Part 2) trial in patients with treatment-naïve microsatellite stable mCRC. Patients in Part 2 were randomised to receive standard-of-care (control arm) or standard-of-care plus durvalumab and oleclumab (experimental arm). Primary objectives included safety and efficacy.

Results: Seven patients were enrolled in Part 1 and 52 in Part 2 (n = 26 in each arm). Grade ≥3 treatment-emergent …

Optical Genome Mapping Improves The Accuracy Of Classification, Risk Stratification, And Personalized Treatment Strategies For Patients With Acute Myeloid Leukemia, Sanam Loghavi, Qing Wei, Farhad Ravandi, Andres E Quesada, Mark J Routbort, Shimin Hu, Gokce A Toruner, Sa A Wang, Wei Wang, Roberto N Miranda, Shaoying Li, Jie Xu, Courtney D Dinardo, Naval Daver, Tapan M Kadia, Ghayas C Issa, Hagop M Kantarjian, L Jeffrey Medeiros, Guilin Tang

Faculty, Staff and Student Publications

Cytogenomic characterization is crucial for the classification and risk stratification of acute myeloid leukemia (AML), thereby facilitating therapeutic decision-making. We examined the clinical utility of optical genome mapping (OGM) in 159 AML patients (103 newly diagnosed and 56 refractory/relapsed), all of whom also underwent chromosomal banding analysis (CBA), fluorescence in situ hybridization, and targeted next-generation sequencing. OGM detected nearly all clinically relevant cytogenetic abnormalities that SCG identified with >99% sensitivity, provided the clonal burden was above 20%. OGM identified additional cytogenomic aberrations and/or provided information on fusion genes in 77 (48%) patients, including eight patients with normal karyotypes and four …

Identification Of Molecular Signatures In Epicardial Adipose Tissue In Heart Failure With Preserved Ejection Fraction, Shan He, Lei Zhao, Jianjun Zhang, Xinchun Yang, Huagang Zhu

Faculty, Staff and Student Publications

AIMS: The molecular signatures in epicardial adipose tissue (EAT) that contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF) are poorly characterized. In this study, we sought to elucidate molecular signatures including genetic transcripts and long non-coding RNAs (lncRNAs) in EAT that might modulate HFpEF development.

METHODS: RNA sequencing (RNA-seq) was performed to identify differentially expressed lncRNAs and mRNAs in EAT samples from patients with HFpEF (n = 5) and without HF (control, n = 5) who underwent coronary artery bypass grafting. The sequencing results were validated using quantitative real-time PCR (qRT-PCR). Bioinformatics analysis (Gene Ontology and …

Social Determinants Of Health And Surgical Desirability Of Outcome Ranking In Older Veterans, Michael A Jacobs, Yubo Gao, Susanne Schmidt, Paula K Shireman, Michael Mader, Carly A Duncan, Leslie R M Hausmann, Karyn B Stitzenberg, Lillian S Kao, Mary Vaughan Sarrazin, Daniel E Hall

Faculty, Staff and Student Publications

Importance: Evaluating how social determinants of health (SDOH) influence veteran outcomes is crucial, particularly for quality improvement.

Objective: To measure associations between SDOH, care fragmentation, and surgical outcomes using a Desirability of Outcome Ranking (DOOR).

Design, setting, and participants: This was a cohort study of US veterans using data from the Veterans Affairs (VA) Surgical Quality Improvement Program (VASQIP; 2013-2019) limited to patients aged 65 years or older with inpatient stays between 2 and 30 days, merged with multiple data sources, including Medicare. Race and ethnicity data were retrieved from VASQIP, Medicare and Medicaid beneficiary summary files, the Veterans Health …

Targeting The Epidermal Growth Factor Receptor Pathway In Chemotherapy-Resistant Triple-Negative Breast Cancer: A Phase Ii Study, Clinton Yam, Miral Patel, Holly A Hill, Ryan Sun, Roland L Bassett, Elisabeth Kong, Senthil Damodaran, Kimberly B Koenig, Sausan Abouharb, Sadia Saleem, Ajit K Bisen, Rashmi K Murthy, David L Ramirez, Gaiane M Rauch, Beatriz E Adrada, Rosalind P Candelaria, Xiaoping Wang, Elizabeth A Mittendorf, Alastair M Thompson, Jason B White, Elizabeth E Ravenberg, Alyson R Clayborn, Qing-Qing Ding, Daniel J Booser, Oluchi Oke, Abenaa M Brewster, Gabriel N Hortobagyi, Nuhad K Ibrahim, Jennifer K Litton, Vicente Valero, Banu K Arun, Debu Tripathy, Jeffrey T Chang, Ken Chen, Anil Korkut, Stacy L Moulder, Lei Huo, Bora Lim, Naoto T Ueno

Faculty, Staff and Student Publications

Purpose: Epidermal growth factor receptor (EGFR) pathway activation causes chemotherapy resistance, and inhibition of the EGFR pathway sensitizes triple-negative breast cancer (TNBC) cells to chemotherapy in preclinical models. Given the high prevalence of EGFR overexpression in TNBC, we conducted a single-arm phase II study of panitumumab (anti-EGFR monoclonal antibody), carboplatin, and paclitaxel as the second phase of neoadjuvant therapy (NAT) in patients with doxorubicin and cyclophosphamide (AC)-resistant TNBC (NCT02593175).

Patients and methods: Patients with early-stage, AC-resistant TNBC, defined as disease progression or ≤80% reduction in tumor volume after four cycles of AC, were eligible for this study and …

Response To Letter To The Editor Concerning The Article "The Clinical And Economic Impact Of Extended Battery Longevity Of A Substernal Extravascular Implantable Cardioverter Defibrillator"., Bradley P Knight, Nicolas Clémenty, Anish Amin, Ulrika Maria Birgersdotter-Green, Henri Roukoz, Reece Holbrook, Jaimie Manlucu

Heart and Vascular Articles

No abstract provided.

Impact Of Functional Recovery On Patients Having Heart Surgery., Richard J Snow, Lauren Mckown, Geoffrey Blossom, Karen Vogel, Amy Creighton, Jason Shriver, Linda Will, Katie Lentz, Elizabeth Snow, Teresa Caulin-Glaser

Heart and Vascular Articles

OBJECTIVE: To describe the results of a program developed to manage institutional postacute care (IPAC) (postacute skilled nursing, inpatient rehabilitation facility, and long-term acute care) in a CMS Bundled Payments for Care Improvement (BPCI) project for coronary artery bypass graft (CABG) surgery.

STUDY DESIGN: We compared pre- and postutilization patterns during a 3-year period by evaluating risk-adjusted national, state, and other BPCI participant comparisons using a difference-in-differences (DID) analysis in a large urban community tertiary center with a CABG surgery program. Included in the analysis were all Medicare patients receiving CABG surgery at the institution (n = 504), across the …

Genomic Biomarkers To Predict Response To Atezolizumab Plus Bevacizumab Immunotherapy In Hepatocellular Carcinoma: Insights From The Imbrave150 Trial, Sun Young Yim, Sung Hwan Lee, Seung-Woo Baek, Bohwa Sohn, Yun Seong Jeong, Sang-Hee Kang, Kena Park, Hyewon Park, Sunyoung S Lee, Ahmed O Kaseb, Young Nyun Park, Sun-Hee Leem, Michael A Curran, Ji Hoon Kim, Ju-Seog Lee

Faculty, Staff and Student Publications

Background/aims: Combination immunotherapy, exemplified by atezolizumab plus bevacizumab, has become the standard of care for inoperable hepatocellular carcinoma (HCC). However, the lack of predictive biomarkers and limited understanding of response mechanisms remain a challenge.

Methods: Using data from the IMbrave150plus cohort, we applied an immune signature score (ISS) predictor to stratify HCC patients treated with atezolizumab plus bevacizumab or with sorafenib alone into potential high and low response groups. By applying multiple statistical approaches including a Bayesian covariate prediction algorithm, we refined the signature to 10 key genes (ISS10) for clinical use while maintaining similar predictive power to the full …