Medicine and Health Sciences Commons^™

Contemporary Report Of Surgical Outcomes After Single-Stage Total Pancreatectomy: A 10-Year Experience, Nitzan Zohar, Luke Kowal, David Moskal, Francesca Ponzini, George Sun, Ryan J. Lamm, John Williamson, Avinoam Nevler, Harish Lavu, Warren R. Maley, Charles J. Yeo, Wilbur B. Bowne

Department of Surgery Faculty Papers

BACKGROUND: Surgeons rarely perform elective total pancreatectomy (TP). Our study seeks to report surgical outcomes in a contemporary series of single-stage (SS) TP patients.

METHODS: Between the years 2013 to 2023 we conducted a retrospective review of 60 consecutive patients who underwent SSTP. Demographics, pathology, treatment-related variables, and survival were recorded and analyzed.

RESULTS: SSTP consisted of 3% (60/1859) of elective pancreas resections conducted. Patient median age was 68 years. Ninety percent of these patients (n = 54) underwent SSTP for pancreatic ductal adenocarcinoma (PDAC). Conversion from a planned partial pancreatectomy to TP occurred intraoperatively in 31 (52%) patients. Fifty-nine …

Stat5 Induces Androgen Receptor (Ar) Gene Transcription In Prostate Cancer And Offers A Druggable Pathway To Target Ar Signaling, Cristina Maranto, Lavannya Sabharwal, Vindhya Udhane, Samuel P. Pitzen, Braedan Mccluskey, Songyan Qi, Christine O'Connor, Savita Devi, Scott Johnson, Kenneth Jacobsohn, Anjishnu Banerjee, Kenneth A. Iczkowski, Liang Wang, Scott M. Dehm, Marja T. Nevalainen

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Androgen receptor (AR) drives prostate cancer (PC) growth and progression, and targeting AR signaling is the mainstay of pharmacological therapies for PC. Resistance develops relatively fast as a result of refueled AR activity. A major gap in the field is the lack of understanding of targetable mechanisms that induce persistent AR expression in castrate-resistant PC (CRPC). This study uncovers an unexpected function of active Stat5 signaling, a known promoter of PC growth and clinical progression, as a potent inducer of AR gene transcription. Stat5 suppression inhibited AR gene transcription in preclinical PC models and reduced the levels of wild-type, mutated, …

Paired Single-B-Cell Transcriptomics And Receptor Sequencing Reveal Activation States And Clonal Signatures That Characterize B Cells In Acute Myeloid Leukemia, Shengnan Guo, Gopi S Mohan, Bofei Wang, Tianhao Li, Naval Daver, Yuting Zhao, Patrick K Reville, Dapeng Hao, Hussein A Abbas

Faculty, Staff and Student Publications

BACKGROUND: Acute myeloid leukemia (AML) is associated with a dismal prognosis. Immune checkpoint blockade (ICB) to induce antitumor activity in AML patients has yielded mixed results. Despite the pivotal role of B cells in antitumor immunity, a comprehensive assessment of B lymphocytes within AML's immunological microenvironment along with their interaction with ICB remains rather constrained.

METHODS: We performed an extensive analysis that involved paired single-cell RNA and B-cell receptor (BCR) sequencing on 52 bone marrow aspirate samples. These samples included 6 from healthy bone marrow donors (normal), 24 from newly diagnosed AML patients (NewlyDx), and 22 from 8 relapsed or …

Comprehensive Characterization Of Ifnγ Signaling In Acute Myeloid Leukemia Reveals Prognostic And Therapeutic Strategies, Bofei Wang, Patrick K Reville, Mhd Yousuf Yassouf, Fatima Z Jelloul, Christopher Ly, Poonam N Desai, Zhe Wang, Pamella Borges, Ivo Veletic, Enes Dasdemir, Jared K Burks, Guilin Tang, Shengnan Guo, Araceli Isabella Garza, Cedric Nasnas, Nicole R Vaughn, Natalia Baran, Qing Deng, Jairo Matthews, Preethi H Gunaratne, Dinler A Antunes, Suhendan Ekmekcioglu, Koji Sasaki, Miriam B Garcia, Branko Cuglievan, Dapeng Hao, Naval Daver, Michael R Green, Marina Konopleva, Andrew Futreal, Sean M Post, Hussein A Abbas

Faculty, Staff and Student Publications

Interferon gamma (IFNγ) is a critical cytokine known for its diverse roles in immune regulation, inflammation, and tumor surveillance. However, while IFNγ levels were elevated in sera of most newly diagnosed acute myeloid leukemia (AML) patients, its complex interplay in AML remains insufficiently understood. We aim to characterize these complex interactions through comprehensive bulk and single-cell approaches in bone marrow of newly diagnosed AML patients. We identify monocytic AML as having a unique microenvironment characterized by IFNγ producing T and NK cells, high IFNγ signaling, and immunosuppressive features. IFNγ signaling score strongly correlates with venetoclax resistance in primary AML patient …

Loss Of The Endoplasmic Reticulum Protein Tmem208 Affects Cell Polarity, Development, And Viability, Debdeep Dutta, Oguz Kanca, Rishi V Shridharan, Paul C Marcogliese, Benjamin Steger, Marie Morimoto, F Graeme Frost, Ellen Macnamara, Michael F Wangler, Shinya Yamamoto, Andreas Jenny, David Adams, May C Malicdan, Hugo J Bellen

Faculty, Staff and Students Publications

Nascent proteins destined for the cell membrane and the secretory pathway are targeted to the endoplasmic reticulum (ER) either posttranslationally or cotranslationally. The signal-independent pathway, containing the protein TMEM208, is one of three pathways that facilitates the translocation of nascent proteins into the ER. The in vivo function of this protein is ill characterized in multicellular organisms. Here, we generated a CRISPR-induced null allele of the fruit fly ortholog

H2a.Z Histone Variants Facilitate Hdaci-Dependent Removal Of H3.3k27m Mutant Protein In Pediatric High-Grade Glioma Cells, Katarzyna B Leszczynska, Francisca N L Vitorino, Benjamin A Garcia, Et Al.

2020-Current year OA Pubs

Diffuse intrinsic pontine gliomas (DIPGs) are deadly pediatric brain tumors, non-resectable due to brainstem localization and diffusive growth. Over 80% of DIPGs harbor a mutation in histone 3 (H3.3 or H3.1) resulting in a lysine-to-methionine substitution (H3K27M). Patients with DIPG have a dismal prognosis with no effective therapy. We show that histone deacetylase (HDAC) inhibitors lead to a significant reduction in the H3.3K27M protein (up to 80%) in multiple glioma cell lines. We discover that the SB939-mediated H3.3K27M loss is partially blocked by a lysosomal inhibitor, chloroquine. The H3.3K27M loss is facilitated by co-occurrence of H2A.Z, as evidenced by the …

Intensive Care Risk And Long-Term Outcomes In Pediatric Allogeneic Hematopoietic Cell Transplant Recipients, Matt S Zinter, Robert J Hayashi, Et Al.

2020-Current year OA Pubs

Allogeneic hematopoietic cell transplantation (HCT) can be complicated by life-threatening organ toxicity and infection necessitating intensive care. Epidemiologic data have been limited by single-center studies, poor database granularity, and a lack of long-term survivors. To identify contemporary trends in intensive care unit (ICU) use and long-term outcomes, we merged data from the Center for International Blood and Marrow Transplant Research and the Virtual Pediatric Systems databases. We identified 6995 pediatric patients with HCT aged ≤21 years who underwent first allogeneic HCT between 2008 and 2014 across 69 centers in the United States or Canada and followed patients until the year …

Bridging Therapy With Axicabtagene Ciloleucel For Large B-Cell Lymphoma: Results From The Us Lymphoma Car-T Consortium, Michael D Jain, Miriam T Jacobs, Feng Gao, Armin Ghobadi, Et Al.

2020-Current year OA Pubs

During the manufacturing period of autologous chimeric antigen receptor (CAR) T-cell therapy, patients may experience a decline in their condition due to cancer progression. In this study, we investigated the impact of bridging therapy (BT) on the outcome of patients with relapsed/refractory large B-cell lymphoma who received antilymphoma treatment between leukapheresis and axicabtagene ciloleucel (axi-cel) infusion. We conducted our analysis using data from the multicenter US Lymphoma CAR-T Consortium, with a median follow-up of 33 months (range, 4.3-42.1). Out of the 298 patients who underwent leukapheresis, 275 patients received axi-cel. A total 52% of patients (n = 143) who received …

Comparative Efficacy, Quality Of Life, Safety, And Tolerability Of Atogepant And Rimegepant In Migraine Prevention: A Matching-Adjusted Indirect Comparison Analysis, Cristina Tassorelli, Kateryna Onishchenko, Rashmi B. Halker Singh, Molly Duan, Laure Dupont-Benjamin, Matthew Hemstock, Corey Voller, Peter Mcallister, Stephanie J. Nahas, Pranav Gandhi, Jessica Ailani

Department of Neurology Faculty Papers

BACKGROUND: Comparative evaluations of preventive migraine treatments can help inform clinical decision making for managing migraine in clinical practice.

METHODS: An anchored matching-adjusted indirect comparison analysis was conducted using pooled participant-level data from two phase 3 atogepant trials (ADVANCE and PROGRESS) and one phase 2/3 rimegepant trial (BHV3000-305) to evaluate the relative efficacy and safety/tolerability of atogepant and rimegepant as preventive migraine treatments. Participants receiving atogepant 60 mg once daily, rimegepant orally disintegrating tablet 75 mg once every other day, and placebo were included. Only participants meeting the BHV3000-305 inclusion/exclusion criteria were analyzed: ≥6 monthly migraine days and ≤18 monthly …

A Robust Quality Infrastructure Is Key To Safe And Effective Delivery Of Immune Effector Cells: How Fact-Finding Can Help, Kevin J Curran, Sarah Nikiforow, Carlos Bachier, Yen-Michael Hsu, David Maloney, Marcela V Maus, Philip Mccarthy, David Porter, Patricia Shi, Elizabeth J Shpall, Basem William, Kara Wacker, Phyllis Warkentin, Helen E Heslop

Faculty, Staff and Students Publications

Immune effector cells (IECs) include a broad range of immune cells capable of modulating several disease states, including malignant and nonmalignant conditions. The growth in the use of IECs as both investigational and commercially available products requires medical institutions to develop workflows/processes to safely implement and deliver transformative therapy. Adding to the complexity of this therapy are the variety of targets, diseases, sources, and unique toxicities that a patient experiences following IEC therapy. For over 25 years, the Foundation for the Accreditation of Cellular Therapy (FACT) has established a standard for the use of cellular therapy, initially with hematopoietic cell …

Association Of Plasma Ykl-40 With Mri, Csf, And Cognitive Markers Of Brain Health And Dementia, Matthew P Pase, Jayandra J Himali, Raquel Puerta, Alexa S Beiser, Mitzi M Gonzales, Claudia L Satizabal, Qiong Yang, Hugo J Aparicio, Daniel J Kojis, Charles S Decarli, Oscar L Lopez, Will Longstreth, Vilmundur Gudnason, Thomas H Mosley, Joshua C Bis, Alison Fohner, Bruce M Psaty, Mercè Boada, Pablo García-González, Sergi Valero, Marta Marquié, Russell Tracy, Lenore J Launer, Agustín Ruiz, Myriam Fornage, Sudha Seshadri

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Higher YKL-40 levels in the CSF are a known biomarker of brain inflammation. We explored the utility of plasma YKL-40 as a biomarker for accelerated brain aging and dementia risk.

METHODS: We performed cross-sectional and prospective analyses of 4 community-based cohorts in the United States or Europe: the Age, Gene/Environment Susceptibility-Reykjavik Study, Atherosclerosis Risk in the Communities study, Coronary Artery Risk Development in Young Adults study, and Framingham Heart Study (FHS). YKL-40 was measured from stored plasma by a single laboratory using Mesoscale Discovery with levels log transformed and standardized within each cohort. Outcomes included MRI total …

Bridging Therapy With Axicabtagene Ciloleucel For Large B-Cell Lymphoma: Results From The Us Lymphoma Car-T Consortium, Michael D Jain, Miriam T Jacobs, Feng Gao, Loretta J Nastoupil, Jay Y Spiegel, Yi Lin, Saurabh Dahiya, Matthew Lunning, Lazaros Lekakis, Patrick Reagan, Olalekan Oluwole, Joseph Mcguirk, Abhinav Deol, Alison R Sehgal, Andre Goy, Brian T Hill, Charalambos Andreadis, Javier Munoz, Julio C Chavez, N Nora Bennani, Aaron P Rapoport, Julie M Vose, David Miklos, Sattva S Neelapu, Frederick L Locke, Armin Ghobadi

Faculty, Staff and Student Publications

During the manufacturing period of autologous chimeric antigen receptor (CAR) T-cell therapy, patients may experience a decline in their condition due to cancer progression. In this study, we investigated the impact of bridging therapy (BT) on the outcome of patients with relapsed/refractory large B-cell lymphoma who received antilymphoma treatment between leukapheresis and axicabtagene ciloleucel (axi-cel) infusion. We conducted our analysis using data from the multicenter US Lymphoma CAR-T Consortium, with a median follow-up of 33 months (range, 4.3-42.1). Out of the 298 patients who underwent leukapheresis, 275 patients received axi-cel. A total 52% of patients (n = 143) who received …

Prognostic Risk Signature In Patients With Acute Myeloid Leukemia Treated With Hypomethylating Agents And Venetoclax, Alex Bataller, Alexandre Bazinet, Courtney D Dinardo, Abhishek Maiti, Gautam Borthakur, Naval G Daver, Nicholas J Short, Elias J Jabbour, Ghayas C Issa, Naveen Pemmaraju, Musa Yilmaz, Guillermo Montalban-Bravo, Koichi Takahashi, Sanam Loghavi, Guillermo Garcia-Manero, Farhad Ravandi, Hagop M Kantarjian, Tapan M Kadia

Faculty, Staff and Student Publications

Hypomethylating agents (HMAs) and venetoclax (Ven) represent the standard of care for patients with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy. However, the European LeukemiaNet (ELN) risk classifications have been validated for patients treated with intensive therapy. In this study, we validate a recently proposed new molecular prognostic risk signature (mPRS) for patients with AML treated with HMAs and Ven. This classification allocated patients to favorable, intermediate (N/KRAS or FLT3-internal tandem duplication mutations), and lower (TP53 mutations) benefit groups. We retrospectively analyzed 159 patients treated with HMA and Ven. The mPRS classification allocated 74 (47%), 31 (19%), …

A Phase 1/2 Study Of Mini-Hyper-Cvd Plus Venetoclax In Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia, Nicholas J Short, Elias Jabbour, Nitin Jain, Jayastu Senapati, Lewis Nasr, Fadi G Haddad, Zhenhua Li, Yu-Chih Hsiao, Jun J Yang, Naveen Pemmaraju, Maro Ohanian, William G Wierda, Guillermo Montalban-Bravo, Gautam Borthakur, Lina Han, Lianchun Xiao, Xuelin Huang, Regina Abramova, Min Zhao, Rebecca Garris, Marina Konopleva, Farhad Ravandi, Hagop Kantarjian

Faculty, Staff and Student Publications

Preclinical studies suggest that Bcl-2 inhibition with venetoclax has antileukemic activity in acute lymphoblastic leukemia (ALL) and may synergize with conventional chemotherapy. We designed a phase 1/2 clinical trial to evaluate the safety and efficacy of low-intensity chemotherapy in combination with venetoclax in adults with relapsed or refractory ALL. Patients received the mini-hyper-CVD regimen (dose-attenuated hyperfractionated cyclophosphamide, vincristine, and dexamethasone alternating with methotrexate and cytarabine) in combination with venetoclax (200 mg or 400 mg daily) on days 1 to 14 in cycle 1 and on days 1 to 7 in consolidation cycles. Twenty-two patients were treated. The median number of …

Differential Upregulation Of Th1/Th17-Associated Proteins And Pd-L1 In Granulomatous Mycosis Fungoides, Mario L Marques-Piubelli, Jesus Navarrete, Debora A Ledesma, Courtney W Hudgens, Rossana N Lazcano, Ali Alani, Auris Huen, Madeleine Duvic, Priyadharsini Nagarajan, Phyu P Aung, Ignacio I Wistuba, Jonathan L Curry, Roberto N Miranda, Carlos A Torres-Cabala

Faculty, Staff and Student Publications

Granulomatous Mycosis Fungoides (GMF) is a rare form of mycosis fungoides (MF) characterized by a granulomatous infiltrate associated with the neoplastic lymphoid population and is considered to have a worse prognosis compared with regular MF. The upregulation of the T helper (Th) axis, especially Th17, plays an important role in the pathogenesis of several inflammatory/infectious granulomatous cutaneous diseases, but its role in GMF is still not elucidated to date. In this study, we evaluated the immunohistochemical expression of Th1 (Tbet), Th2 (GATA-3), Th17 (RORγT), T regulatory (Foxp3), and immune checkpoint (IC) (PD-1 and PD-L1) markers in a cohort of patients …

Mortality After Major Cardiovascular Events In Survivors Of Childhood Cancer, Wendy Bottinor, Cindy Im, David R Doody, Saro H Armenian, Alexander Arynchyn, Borah Hong, Rebecca M Howell, David R Jacobs, Kirsten K Ness, Kevin C Oeffinger, Alexander P Reiner, Gregory T Armstrong, Yutaka Yasui, Eric J Chow

Faculty, Staff and Student Publications

Background: Adult survivors of childhood cancer are at risk for cardiovascular events.

Objectives: In this study, we sought to determine the risk for mortality after a major cardiovascular event among childhood cancer survivors compared with noncancer populations.

Methods: All-cause and cardiovascular cause-specific mortality risks after heart failure (HF), coronary artery disease (CAD), or stroke were compared among survivors and siblings in the Childhood Cancer Survivor Study (CCSS) and participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Cox proportional hazard regression models were used to estimate HRs and 95% CIs between groups, adjusted for demographic and clinical …

A Robust Quality Infrastructure Is Key To Safe And Effective Delivery Of Immune Effector Cells: How Fact-Finding Can Help., Kevin J Curran, Sarah Nikiforow, Carlos Bachier, Yen-Michael Hsu, David Maloney, Marcela V Maus, Philip Mccarthy, David Porter, Patricia Shi, Elizabeth J Shpall, Basem William, Kara Wacker, Phyllis Warkentin, Helen E Heslop

Oncology Articles

Immune effector cells (IECs) include a broad range of immune cells capable of modulating several disease states, including malignant and nonmalignant conditions. The growth in the use of IECs as both investigational and commercially available products requires medical institutions to develop workflows/processes to safely implement and deliver transformative therapy. Adding to the complexity of this therapy are the variety of targets, diseases, sources, and unique toxicities that a patient experiences following IEC therapy. For over 25 years, the Foundation for the Accreditation of Cellular Therapy (FACT) has established a standard for the use of cellular therapy, initially with hematopoietic cell …

Efficacy And Safety Of Daxibotulinumtoxina For Injection In Cervical Dystonia: Aspen-1 Phase 3 Randomized Controlled Trial, Cynthia L Comella, Joseph Jankovic, Robert A Hauser, Atul T Patel, Marta D Banach, Edvard Ehler, Domenico Vitarella, Roman G Rubio, Todd M Gross, Aspen-1 Study Group

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVES: ASPEN-1 was a phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy, duration of response, and safety of 2 doses of DaxibotulinumtoxinA for Injection (DAXI), a novel botulinum toxin type A formulation in participants with cervical dystonia (CD).

METHODS: Adults (aged 18-80 years) with moderate-to-severe CD (Toronto Western Spasmodic Torticollis Rating Scale [TWSTRS] total score ≥20) were enrolled at 60 sites across 9 countries in Europe and North America. Participants were randomized (3:3:1) to single-dose intramuscular DAXI 125U, 250U, or placebo and followed for up to 36 weeks after injection. The primary end point was change …

Rbpms Regulates Cardiomyocyte Contraction And Cardiac Function Through Rna Alternative Splicing, Peiheng Gan, Zhaoning Wang, Svetlana Bezprozvannaya, John R Mcanally, Wei Tan, Hui Li, Rhonda Bassel-Duby, Ning Liu, Eric N Olson

Faculty, Staff and Student Publications

Aims: RNA binding proteins play essential roles in mediating RNA splicing and are key post-transcriptional regulators in the heart. Our recent study demonstrated that RBPMS (RNA binding protein with multiple splicing) is crucial for cardiac development through modulating mRNA splicing, but little is known about its functions in the adult heart. In this study, we aim to characterize the post-natal cardiac function of Rbpms and its mechanism of action.

Methods and results: We generated a cardiac-specific knockout mouse line and found that cardiac-specific loss of Rbpms caused severe cardiomyocyte contractile defects, leading to dilated cardiomyopathy and early lethality in adult …

Protein-Folding Chaperones Predict Structure-Function Relationships And Cancer Risk In Brca1 Mutation Carriers, Brant Gracia, Patricia Montes, Angelica Maria Gutierrez, Banu Arun, Georgios Ioannis Karras

Faculty, Staff and Student Publications

Predicting the risk of cancer mutations is critical for early detection and prevention, but differences in allelic severity of human carriers confound risk predictions. Here, we elucidate protein folding as a cellular mechanism driving differences in mutation severity of tumor suppressor BRCA1. Using a high-throughput protein-protein interaction assay, we show that protein-folding chaperone binding patterns predict the pathogenicity of variants in the BRCA1 C-terminal (BRCT) domain. HSP70 selectively binds 94% of pathogenic BRCA1-BRCT variants, most of which engage HSP70 more than HSP90. Remarkably, the magnitude of HSP70 binding linearly correlates with loss of folding and function. We identify a prevalent …

Gamma Delta T Cells In Acute Myeloid Leukemia: Biology And Emerging Therapeutic Strategies, Adishwar Rao, Akriti Agrawal, Gautam Borthakur, Venkata Lokesh Battula, Abhishek Maiti

Faculty, Staff and Student Publications

γδ T cells play an important role in disease control in acute myeloid leukemia (AML) and have become an emerging area of therapeutic interest. These cells represent a minor population of T lymphocytes with intrinsic abilities to recognize antigens in a major histocompatibility complex-independent manner and functionally straddle the innate and adaptive immunity interface. AML shows high expression of phosphoantigens and UL-16 binding proteins that activate the Vδ2 and Vδ1 subtypes of γδ T cells, respectively, leading to γδ T cell-mediated cytotoxicity. Insights from murine models and clinical data in humans show improved overall survival, leukemia-free survival, reduced risk of …

Aging Impairs The Osteocytic Regulation Of Collagen Integrity And Bone Quality, Charles A Schurman, Serra Kaya, Neha Dole, Nadja M Maldonado Luna, Natalia Castillo, Ryan Potter, Jacob P Rose, Joanna Bons, Christina D King, Jordan B Burton, Birgit Schilling, Simon Melov, Simon Tang, Eric Schaible, Tamara Alliston

2020-Current year OA Pubs

Poor bone quality is a major factor in skeletal fragility in elderly individuals. The molecular mechanisms that establish and maintain bone quality, independent of bone mass, are unknown but are thought to be primarily determined by osteocytes. We hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling (PLR), which maintains bone material properties. We examined bones from young and aged mice with osteocyte-intrinsic repression of TGFβ signaling (TβRII

Improving Safety And Preventing Falls Using An Evidence-Based, Front-Line Staff Huddling Practice: Protocol For A Pragmatic Trial To Increase Quality Of Care In State Veterans Homes, Princess Nash, Valerie Clark, Eleanor Mcconnell, Whitney Mills, Robert Morgan, Camilla Pimentel, Katherine Ritchey, Cari Levy, A Lynn Snow, Christine Hartmann

Faculty, Staff and Student Publications

Introduction: Falls in nursing homes are a major cause for decreases in residents' quality of life and overall health. This study aims to reduce resident falls by implementing the LOCK Falls Programme, an evidence-based quality improvement intervention. The LOCK Falls Programme involves the entire front-line care team in (1) focusing on evidence of positive change, (2) collecting data through systematic observation and (3) facilitating communication and coordination of care through the practice of front-line staff huddles.

Methods and analysis: The study protocol describes a mixed-methods, 4-year hybrid (type 2) effectiveness-implementation study in State Veterans Homes in the USA. The study …

Medication Utilization For Patients With Chronic Rhinosinusitis With Nasal Polyposis (Crswnp) And Asthma In 12 Months Pre- And Post-Dupilumab Initiation, Emily Garvey, Bita Naimi, Alexander Duffy, Chase Kahn, Douglas Farquhar, Marc Rosen, Mindy Rabinowitz, Damaris Pena Evertz, Jessica Most, Elina Toskala, Gurston G. Nyquist

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Key Points:

• This study examines the impact of dupilumab on medication use for chronic rhinosinusitis with nasal polyposis (CRSwNP) and asthma patients.
• Patients on dupilumab had a reduction in oral/inhaled/topical steroids, antibiotics, and leukotriene receptor antagonists (LTRAs).
• The reduction in medication use had no impact on total polyp or SNOT-22 scores.

Should We Stent Vulnerable, But Asymptomatic, Lesions?, Nils P Johnson, K Lance Gould, Jagat Narula

Faculty, Staff and Student Publications

No abstract provided.

Racial Discrimination, Knowledge, And Health Outcomes: The Mediating Role Of Hepatitis B-Related Stigma Among Patients With Chronic Hepatitis B, Julia G. Katcher, Ann C. Klassen, Hie-Won Hann, Mimi Chang, Hee-Soon Juon

Department of Medical Oncology Faculty Papers

It is well described in current literature that Hepatitis B virus (HBV) affects Asian Americans more than any other racial group in the United States and that there is a stigma attached to this condition. The effects of stigma can be lasting, penetrating physiologically and psychologically, yet few studies have focused on the consequences of this phenomenon. The purpose of this study was to examine the mediating role of stigma in the effect of racial discrimination and knowledge (of HBV sequelae) on health status of Korean Americans with chronic hepatitis B (CHB). Three hundred sixty-five CHB patients were recruited and …

Fully Automated Deep Learning Based Auto-Contouring Of Liver Segments And Spleen On Contrast-Enhanced Ct Images, Aashish C Gupta, Guillaume Cazoulat, Mais Al Taie, Sireesha Yedururi, Bastien Rigaud, Austin Castelo, John Wood, Cenji Yu, Caleb O'Connor, Usama Salem, Jessica Albuquerque Marques Silva, Aaron Kyle Jones, Molly Mcculloch, Bruno C Odisio, Eugene J Koay, Kristy K Brock

Faculty, Staff and Student Publications

Manual delineation of liver segments on computed tomography (CT) images for primary/secondary liver cancer (LC) patients is time-intensive and prone to inter/intra-observer variability. Therefore, we developed a deep-learning-based model to auto-contour liver segments and spleen on contrast-enhanced CT (CECT) images. We trained two models using 3d patch-based attention U-Net ([Formula: see text] and 3d full resolution of nnU-Net ([Formula: see text] to determine the best architecture ([Formula: see text]. BA was used with vessels ([Formula: see text] and spleen ([Formula: see text] to assess the impact on segment contouring. Models were trained, validated, and tested on 160 ([Formula: see text]), …

Polyaminer-Bulk Is A Deep Learning-Based Algorithm That Decodes Alternative Polyadenylation Dynamics From Bulk Rna-Seq Data, Venkata Soumith Jonnakuti, Eric J Wagner, Mirjana Maletić-Savatić, Zhandong Liu, Hari Krishna Yalamanchili

Faculty, Staff and Students Publications

Alternative polyadenylation (APA) is a key post-transcriptional regulatory mechanism; yet, its regulation and impact on human diseases remain understudied. Existing bulk RNA sequencing (RNA-seq)-based APA methods predominantly rely on predefined annotations, severely impacting their ability to decode novel tissue- and disease-specific APA changes. Furthermore, they only account for the most proximal and distal cleavage and polyadenylation sites (C/PASs). Deconvoluting overlapping C/PASs and the inherent noisy 3' UTR coverage in bulk RNA-seq data pose additional challenges. To overcome these limitations, we introduce PolyAMiner-Bulk, an attention-based deep learning algorithm that accurately recapitulates C/PAS sequence grammar, resolves overlapping C/PASs, captures non-proximal-to-distal APA changes, …

Juvenile Eosinophilic Fasciitis: A Single Center Case Series, Leigh A Stubbs, Oluwaseun Ogunbona, Emily Beil, Vibha Szafron, Adekunle Adesina, Sara Anvari, Jamie Lai, Andrea Ramirez, Matthew G Ditzler, Marietta Deguzman

Faculty, Staff and Students Publications

BACKGROUND: Eosinophilic fasciitis (EF) is a rare disease characterized by skin induration and musculoskeletal abnormalities. Diagnostic criteria for EF are based on adult populations. There is a need to expand the literature on EF in children due to limited reported cases and potential differences compared to adults.

METHODS: We conducted a retrospective review of medical records for six pediatric patients diagnosed with EF at our institution between November 2011 and April 2023. Inclusion criteria required patients to be under 18 years of age at the time of diagnosis and to have confirmed diagnosis through clinical history, imaging, and histology.

RESULTS: …

Impaired Bone Morphogenetic Protein (Bmp) Signaling Pathways Disrupt Decidualization In Endometriosis, Zian Liao, Suni Tang, Peixin Jiang, Ting Geng, Dominique I Cope, Timothy N Dunn, Joie Guner, Linda Alpuing Radilla, Xiaoming Guan, Diana Monsivais

Faculty, Staff and Students Publications

Endometriosis is linked to increased infertility and pregnancy complications due to defective endometrial decidualization. We hypothesized that identification of altered signaling pathways during decidualization could identify the underlying cause of infertility and pregnancy complications. Our study reveals that transforming growth factor β (TGFβ) pathways are impaired in the endometrium of individuals with endometriosis, leading to defective decidualization. Through detailed transcriptomic analyses, we discovered abnormalities in TGFβ signaling pathways and key regulators, such as SMAD4, in the endometrium of affected individuals. We also observed compromised activity of bone morphogenetic proteins (BMP), a subset of the TGFβ family, that control endometrial receptivity. …