Medical Specialties Commons^™

Pegvaliase For The Treatment Of Phenylketonuria: Final Results Of A Long-Term Phase 3 Clinical Trial Program, Cary O Harding, Nicola Longo, Hope Northrup, Stephanie Sacharow, Rani Singh, Janet A Thomas, Jerry Vockley, Roberto T Zori, Kaleigh Bulloch Whitehall, Joshua Lilienstein, Kristin Lindstrom, Drew G Levy, Shaun Jones, Barbara K Burton

Faculty, Staff and Student Publications

Phenylketonuria (PKU) is a genetic disorder caused by deficiency of the enzyme phenylalanine hydroxylase (PAH), which results in phenylalanine (Phe) accumulation in the blood and brain, and requires lifelong treatment to keep blood Phe in a safe range. Pegvaliase is an enzyme-substitution therapy approved for individuals with PKU and uncontrolled blood Phe concentrations (>600 μmol/L) despite prior management. Aggregated results from the PRISM clinical trials demonstrated substantial and sustained reductions in blood Phe with a manageable safety profile, but also noted individual variation in time to and dose needed for a first response. This analysis reports longer-term aggregate findings …

Opioid Risk Tool, In-Hospital Opioid Exposure, And Opioid Demand Predict Pain Outcomes Following Traumatic Injury, Danielle A Kessler, Heather E Webber, Constanza De Dios, Jin H Yoon, Joy M Schmitz, Scott D Lane, John A Harvin, Angela M Heads, Charles E Green, Shweta Kapoor, Angela L Stotts, Kandice L Motley, Robert Suchting

Faculty, Staff and Student Publications

Prescribed opioids are a mainstay pain treatment after traumatic injury, but a subgroup of patients may be at risk for continued opioid use. We evaluated the predictive utility of a traditional screening tool, the Opioid Risk Tool (ORT), and two other measures: average in-hospital milligram morphine equivalents (MME) per day and an assessment of opioid demand in predicting pain outcomes. Assessments of pain-related outcomes (pain intensity, interference, injury-related stress, and need for additional pain treatment) were administered at 2 weeks and 12 months post-discharge in a sample of 34 patients hospitalized for traumatic injury. Bayesian linear models were used to …

Current Gaps In Emergency Medicine Core Content Education For Oncologic Emergencies: A Targeted Needs Assessment, Monica K Wattana, Angela Lindsay, Moira Davenport, Nicholas R Pettit, Jazmin R Menendez, Ziyi Li, Demis N Lipe, Aiham Qdaisat, Jason J Bischof

Faculty, Staff and Student Publications

Objective: The core content of emergency medicine (EM) residency training includes the management of oncologic emergencies; however, documented knowledge gaps continue to exist in this subtopic. This study represents a targeted needs assessment as indicated by Step 2 of Kern's curriculum design to determine the specific training gaps to be addressed within the oncologic EM curriculum.

Methods: A multi-institutional cross-sectional survey of oncologists (surgical and medical) and emergency physicians (attendings and residents) was conducted during 2023 at five institutions. The voluntary survey consisted of general and specialty-specific questions exploring gaps in oncologic emergency-specific training/education topics. Descriptive statistics reported responses as …

Liver Late Effects In Childhood Cancer Survivors Treated With Radiation Therapy: A Pentec Comprehensive Review, Matthew D Hall, Rebecca M Howell, Andrew Jackson, Constance A Owens, Soleil Hernandez, Sharon M Castellino, Cecile M Ronckers, Louis S Constine, Julie A Bradley

Faculty, Staff and Student Publications

Purpose: A pediatric normal tissue effects in the clinic (PENTEC) comprehensive review of patients with childhood cancer who received radiation therapy (RT) to the liver was performed to develop models that may inform RT dose constraints for the liver and improve risk forecasting of toxicities.

Methods and materials: A systematic literature search was performed to identify published data on hepatic toxicities in children. Treatment and outcome data were extracted and used to generate normal tissue complication probability (NTCP) models. Complications from both whole and partial liver irradiation were considered. For whole liver irradiation, total body irradiation and non-total body irradiation …

Pediatric Normal Tissue Effects In The Clinic (Pentec): An International Collaboration To Assess Normal Tissue Radiation Dose-Volume-Response Relationships For Children With Cancer, Louis S Constine, Arthur J Olch, Andrew Jackson, Chia-Ho Hua, Cecile M Ronckers, Michael T Milano, Karen J Marcus, Ellen Yorke, David C Hodgson, Rebecca M Howell, Melissa M Hudson, Jacqueline P Williams, Brian Marples, Leontien C M Kremer, Lawrence B Marks, Søren M Bentzen

Faculty, Staff and Student Publications

No abstract provided.

The Impact Of Routine Vaccinations On Alzheimer’S Disease Risk In Persons 65 Years And Older: A Claims-Based Cohort Study Using Propensity Score Matching, Sseu-Pei Hwang, Catherine Denicourt

Faculty, Staff and Student Publications

The dysregulation of ribosome biogenesis is a hallmark of cancer, facilitating the adaptation to altered translational demands essential for various aspects of tumor progression. This review explores the intricate interplay between ribosome biogenesis and cancer development, highlighting dynamic regulation orchestrated by key oncogenic signaling pathways. Recent studies reveal the multifaceted roles of ribosomes, extending beyond protein factories to include regulatory functions in mRNA translation. Dysregulated ribosome biogenesis not only hampers precise control of global protein production and proliferation but also influences processes such as the maintenance of stem cell-like properties and epithelial-mesenchymal transition, contributing to cancer progression. Interference with ribosome …

Author Correction: Concurrent Intrathecal And Intravenous Nivolumab In Leptomeningeal Disease: Phase 1 Trial Interim Results, Isabella C Glitza Oliva, Sherise D Ferguson, Roland Bassett, Alexandra P Foster, Ida John, Tarin D Hennegan, Michelle Rohlfs, Jessie Richard, Masood Iqbal, Tina Dett, Carol Lacey, Natalie Jackson, Theresa Rodgers, Suzanne Phillips, Sheila Duncan, Lauren Haydu, Ruitao Lin, Rodabe N Amaria, Michael K Wong, Adi Diab, Cassian Yee, Sapna P Patel, Jennifer L Mcquade, Grant M Fischer, Ian E Mccutcheon, Barbara J O'Brien, Sudhakar Tummala, Matthew Debnam, Nandita Guha-Thakurta, Jennifer A Wargo, Fernando C L Carapeto, Courtney W Hudgens, Jason T Huse, Michael T Tetzlaff, Elizabeth M Burton, Hussein A Tawbi, Michael A Davies

Faculty, Staff and Student Publications

No abstract provided.

A Novel Missense Variant Located Within The Zinc Finger Domain Of The Gli3 Gene Was Identified In A Vietnamese Pedigree With Index Finger Polydactyly, Thy Ngoc Nguyen, Giang Son Tran, Hai Duc Hoang, Long Giang Nguyen

Faculty, Staff and Student Publications

BACKGROUND: Polydactyly, particularly of the index finger, remains an intriguing anomaly for which no specific gene or locus has been definitively linked to this phenotype. In this study, we conducted an investigation of a three-generation family displaying index finger polydactyly.

METHODS: Exome sequencing was conducted on the patient, with a filtration to identify potential causal variation. Validation of the obtained variant was conducted by Sanger sequencing, encompassing all family members.

RESULTS: Exome analysis uncovered a novel heterozygous missense variant (c.1482A>T; p.Gln494His) at the zinc finger DNA-binding domain of the GLI3 protein within the proband and all affected family members. …

Endothelial Knockdown Of The Tumor Suppressor, Wwox, Increases Inflammation In Ventilator-Induced Lung Injury, Zhenguo Zeng, Eltyeb Abdelwahid, Weiguo Chen, Christian Ascoli, Trinh Pham, Jeffrey R Jacobson, Steven M Dudek, Viswanathan Natarajan, C Marcelo Aldaz, Roberto F Machado, Sunit Singla

Faculty, Staff and Student Publications

Chronic cigarette smoke exposure decreases lung expression of WWOX which is known to protect the endothelial barrier during infectious models of acute respiratory distress syndrome (ARDS). Proteomic analysis of WWOX-silenced endothelial cells (ECs) was done using tandem mass tag mass spectrometry (TMT-MS). WWOX-silenced ECs as well as those isolated from endothelial cell Wwox knockout (EC Wwox KO) mice were subjected to cyclic stretch (18% elongation, 0.5 Hz, 4 h). Cellular lysates and media supernatant were harvested for assays of cellular signaling, protein expression, and cytokine release. These were repeated with dual silencing of WWOX and zyxin. Control and …

Venetoclax And Cobimetinib In Relapsed/Refractory Aml: A Phase 1b Trial, Marina Y Konopleva, Monique Dail, Naval G Daver, Jacqueline S Garcia, Brian A Jonas, Karen W L Yee, Kevin R Kelly, Norbert Vey, Sarit Assouline, Gail J Roboz, Stefania Paolini, Daniel A Pollyea, Agostino Tafuri, Joseph M Brandwein, Arnaud Pigneux, Bayard L Powell, Pierre Fenaux, Rebecca L Olin, Giuseppe Visani, Giovanni Martinelli, Maika Onishi, Jue Wang, Weize Huang, Diana R Dunshee, Habib Hamidi, Marion G Ott, Wan-Jen Hong, Michael Andreeff

Faculty, Staff and Student Publications

Background: Therapies for relapsed/refractory acute myeloid leukemia remain limited and outcomes poor, especially amongst patients who are ineligible for cytotoxic chemotherapy or targeted therapies.

Patients and methods: This phase 1b trial evaluated venetoclax, a B-cell lymphoma-2 (BCL-2) inhibitor, plus cobimetinib, a MEK1/2 inhibitor, in patients with relapsed/refractory acute myeloid leukemia, ineligible for cytotoxic chemotherapy. Two-dimensional dose-escalation was performed for venetoclax dosed daily, and for cobimetinib dosed on days 1-21 of each 28-day cycle.

Results: Thirty patients (median [range] age: 71.5 years [60-84]) received venetoclax-cobimetinib. The most common adverse events (AEs; in ≥40.0% of patients) were diarrhea (80.0%), nausea (60.0%), vomiting …

Covid-19 Vaccine Confidence, Concerns, And Uptake In Children Aged 5 And Older In Calgary, Alberta: A Longitudinal Cohort Study, Emily J Doucette, Leah Ricketson, Tarannum Tarannum, Isabella Alatorre, Joslyn Gray, Cora Constantinescu, Susan Kuhn, Jessica K E Dunn, James D Kellner

Faculty, Staff and Student Publications

OBJECTIVES: Beginning early in the pandemic, there was a worldwide effort to develop effective vaccines against the SARS-CoV-2 virus. Before and after the approval and implementation of vaccines, there were concerns about their need as well as their safety and rapid development. We explored child demographic characteristics and parental concerns to identify factors associated with the decision to vaccinate.

METHODS: A cohort of 1035 children from Calgary was assembled in 2020 to participate in 5 visits every 6 months for survey completion and blood sampling for SARS-CoV-2 antibodies. Visits 1 to 2 occurred before approval of vaccines for children; Visits …

Network Meta-Analysis Of Car T-Cell Therapy For The Treatment Of 3l+ R/R Lbcl After Using Published Comparative Studies, Olalekan O Oluwole, Sattva S Neelapu, Markqayne D Ray, Eve H Limbrick-Oldfield, Sally W Wade, Steve Kanters, Anik R Patel, Frederick L Locke

Faculty, Staff and Student Publications

Introduction: Studies have compared chimeric antigen receptor (CAR) T-cell therapies and salvage chemotherapy in relapsed/refractory large B-cell lymphoma (LBCL) patients, but further evidence of their relative effectiveness is warranted.

Methods: Our systematic review identified studies comparing efficacy and safety outcomes of axicabtagene ciloleucel (axi-cel), lisocabtagene maraleucel (liso-cel) and tisagenlecleucel (tisa-cel) trials to salvage chemotherapy cohorts in LBCL patients with ≥2 prior lines of treatment; and an extended evidence network included indirect comparisons comparing CAR T-cell therapies. We conducted network meta-analyzes using Bayesian hierarchical modeling.

Results: Three studies comparing ZUMA-1 (axi-cel), TRANSCEND (liso-cel) and JULIET (tisa-cel) trials to salvage chemotherapy within …

Glucagon-Like Peptide-1 Receptor Agonist Use And Residual Gastric Content Before Anesthesia, Sudipta Sen, Paul P Potnuru, Nadia Hernandez, Christina Goehl, Caroline Praestholm, Srikanth Sridhar, Omonele O Nwokolo

Faculty, Staff and Student Publications

Importance: Glucagon-like peptide-1 receptor agonist (GLP-1 RA) use is rapidly increasing in the US, driven by its expanded approval for weight management in addition to hyperglycemia management in patients with type 2 diabetes. The perioperative safety of these medications, particularly with aspiration risk under anesthesia, is uncertain.

Objective: To assess the association between GLP-1 RA use and prevalence of increased residual gastric content (RGC), a major risk factor for aspiration under anesthesia, using gastric ultrasonography.

Design, setting, and participants: This cross-sectional study prospectively enrolled patients from a large, tertiary, university-affiliated hospital from June 6 through July 12, 2023. Participants followed …

Immune Checkpoint Blockade Resistance In Lung Cancer: Emerging Mechanisms And Therapeutic Opportunities, Jessica M Konen, Haoyi Wu, Don L Gibbons

Faculty, Staff and Student Publications

Immune checkpoint blockade (ICB) therapy works by inhibiting suppressive checkpoints that become upregulated after T cell activation, like PD-1/PD-L1 and CTLA-4. While the initial FDA approvals of ICB have revolutionized cancer therapies and fueled a burgeoning immuno-oncology field, more recent clinical development of new agents has been slow. Here, focusing on lung cancer, we review the latest research uncovering tumor cell intrinsic and extrinsic ICB resistance mechanisms as major hurdles to treatment efficacy and clinical progress. These include genomic and non-genomic tumor cell alterations, along with host and microenvironmental factors like the microbiome, metabolite accumulation, and hypoxia. Together, these factors …

Prostein Expression On Circulating Tumor Cells As A Prognostic Marker In Metastatic Castration-Resistant Prostate Cancer, Zhenchao Zhang, Rui Luo, William K Kelly, Joshua Chen, Shane Donahue, Kevan Ip, Nathan R Handley, William J Tester, Miranda L Tsang, Felix J Kim, Ronald Myers, Grace Lu-Yao, Jian Gu, Jianqing Lin, Bingshan Li, Chun Wang, Hushan Yang

Faculty, Staff and Student Publications

Background: Identification of emerging molecular biomarkers on circulating tumor cells (CTCs) represents an attractive feature of liquid biopsy that facilitates precision and tailored medicine in the management of metastatic castration-resistant prostate cancer (mCRPC). Prostein is an androgen-regulated transmembrane protein with high prostate specificity. Prostein-positive circulating tumor cell (CTC) was recently suggested to have diagnostic potential; however, no study has been conducted to evaluate its prognostic value in mCRPC.

Methods: CTCs from mCRPC patients were enumerated using the CellSearch System. Prostein-positive CTCs were identified by immunostaining results. The relationships between prostein expression on CTCs and PSA response rate, PSA progression-free survival …

Cardiovascular Disease In Childhood, Adolescent, And Young Adult Cancer Survivors: The Impact Of Family History Of Premature Heart Disease, Amy M Berkman, Clark R Andersen, Andrew P Landstrom, Michelle A T Hildebrandt, Susan C Gilchrist, Michael E Roth

Faculty, Staff and Student Publications

No abstract provided.

Impact Of Knockout Of Dual-Specificity Protein Phosphatase 5 On Structural And Mechanical Properties Of Rat Middle Cerebral Arteries: Implications For Vascular Aging, Chengyun Tang, Huawei Zhang, Jane J Border, Yedan Liu, Xing Fang, Joshua R Jefferson, Andrew Gregory, Claire Johnson, Tae Jin Lee, Shan Bai, Ashok Sharma, Seung Min Shin, Hongwei Yu, Richard J Roman, Fan Fan

Faculty, Staff and Student Publications

Vascular aging influences hemodynamics, elevating risks for vascular diseases and dementia. We recently demonstrated that knockout (KO) of Dusp5 enhances cerebral and renal hemodynamics and cognitive function. This improvement correlates with elevated pPKC and pERK1/2 levels in the brain and kidneys. Additionally, we observed that Dusp5 KO modulates the passive mechanical properties of cerebral and renal arterioles, associated with increased myogenic tone at low pressure, enhanced distensibility, greater compliance, and reduced stiffness. The present study evaluates the structural and mechanical properties of the middle cerebral artery (MCA) in Dusp5 KO rats. We found that vascular smooth muscle cell layers and …

Incidence And Mitigation Of Corneal Pseudomicrocysts Induced By Antibody-Drug Conjugates (Adcs), Ethan S Lindgren, Rongshan Yan, Onur Cil, Alan S Verkman, Matilda F Chan, Gerami D Seitzman, Asim V Farooq, Laura A Huppert, Hope S Rugo, Paula R Pohlmann, Janice Lu, Laura J Esserman, Neel D Pasricha

Faculty, Staff and Student Publications

Purpose of review: This study is to highlight the incidence of corneal pseudomicrocysts in FDA-approved antibody-drug conjugates (ADCs), and success of preventive therapies for pseudomicrocysts and related ocular surface adverse events (AEs).

Recent findings: ADCs are an emerging class of selective cancer therapies that consist of a potent cytotoxin connected to a monoclonal antibody (mAb) that targets antigens expressed on malignant cells. Currently, there are 11 FDA-approved ADCs with over 164 in clinical trials. Various AEs have been attributed to ADCs, including ocular surface AEs (keratitis/keratopathy, dry eye, conjunctivitis, blurred vision, corneal pseudomicrocysts). While the severity and prevalence of ADC-induced …

Cascade Genetic Testing: An Underutilized Pathway To Equitable Cancer Care?, Roni Nitecki Wilke, Erica M Bednar, Sara Pirzadeh-Miller, Sayoni Lahiri, Isabel C Scarinci, Charles A Leath Iii, Melissa K Frey, Karen H Lu, J Alejandro Rauh-Hain

Faculty, Staff and Student Publications

The Precision Medicine Initiative was launched upon the potential of genomic information to tailor medical care. Cascade genetic testing represents a powerful application of precision medicine and involves the process of familial diffusion or the "cascade" of genomic risk information. When an individual (proband) is found to carry a cancer-associated germline pathogenic mutation, the information should be cascaded or shared with at-risk relatives. First degree relatives have a 50% likelihood of carrying the same cancer-associated mutation. This process of cascade testing offers at-risk relatives the opportunity for genetic testing and, for those who also carry the cancer-associated mutation, genetically targeted …

Association Of Tea And Coffee Consumption And Biliary Tract Cancer Risk: The Biliary Tract Cancers Pooling Project, Yu-Han Huang, Erikka Loftfield, Ilona Argirion, Hans-Olov Adami, Demetrius Albanes, Andrew T Chan, Veronika Fedirko, Gary E Fraser, Neal D Freedman, Graham G Giles, Patricia Hartge, Verena Katzke, Synnove F Knutsen, James Lacey, Linda M Liao, Juhua Luo, Roger L Milne, Katie M O'Brien, Ulrike Peters, Jenny N Poynter, Mark P Purdue, Kim Robien, Sven Sandin, Dale P Sandler, Veronica W Setiawan, Jae H Kang, Tracey G Simon, Rashmi Sinha, Trang Vopham, Stephanie J Weinstein, Emily White, Xuehong Zhang, Bin Zhu, Katherine A Mcglynn, Peter T Campbell, Mei-Hsuan Lee, Jill Koshiol

Faculty, Staff and Student Publications

Background and aims: Tea and coffee are widely consumed beverages worldwide. We evaluated their association with biliary tract cancer (BTC) incidence.

Approach and results: We pooled data from 15 studies in the Biliary Tract Cancers Pooling Project to evaluate associations between tea and coffee consumption and biliary tract cancer development. We categorized participants as nondrinkers (0 cup/day), moderate drinkers (>0 and < 3 cups/day), and heavy drinkers (≥3 cups/day). We estimated multivariable HRs and 95% CIs using Cox models. During 29,911,744 person-years of follow-up, 851 gallbladder, 588 intrahepatic bile duct, 753 extrahepatic bile duct, and 458 ampulla of Vater cancer cases were diagnosed. Individuals who drank tea showed a statistically significantly lower incidence rate of gallbladder cancer (GBC) relative to tea nondrinkers (HR=0.77; 95% CI, 0.64-0.91), and intrahepatic bile duct cancer (IHBDC) had an inverse association (HR=0.81; 95% CI, 0.66-1.00). However, no associations were observed for extrahepatic bile duct cancer (EHBDC) or ampulla of Vater cancer (AVC). In contrast, coffee consumption was positively associated with GBC, with a higher incidence rate for individuals consuming more coffee (HR< 3 cups/day =1.29; 95% CI, 1.01-1.66; HR≥3 cups/day =1.49; 95% CI, 1.11-1.99, Ptrend=0.01) relative to coffee nondrinkers. However, there was no association between coffee consumption and GBC when restricted to coffee drinkers. There was little evidence of associations between coffee consumption and other biliary tract cancers.

Conclusions: Tea consumption was associated with a lower incidence of GBC and possibly IHBDC. Further research is warranted to replicate the observed positive association between coffee and GBC.

Development And Standardization Of An Osteoradionecrosis Classification System In Head And Neck Cancer: Implementation Of A Risk-Based Model, Erin E Watson, Katrina Hueniken, Junhyung Lee, Shao Hui Huang, Amr El Maghrabi, Wei Xu, Amy C Moreno, C Jillian Tsai, Ezra Hahn, Andrew J Mcpartlin, Christopher M K L Yao, David P Goldstein, John R De Almeida, John N Waldon, Clifton D Fuller, Andrew J Hope, Salvatore L Ruggiero, Michael Glogauer, Ali A Hosni

Faculty, Staff and Student Publications

Purpose: Osteoradionecrosis of the jaw (ORN) can manifest in varying severity. The aim of this study is to identify ORN risk factors and develop a novel classification to depict the severity of ORN.

Methods: Consecutive patients with head and neck cancer (HNC) treated with curative-intent intensity-modulated radiation therapy (IMRT) (≥45 Gy) from 2011 to 2017 were included. Occurrence of ORN was identified from in-house prospective dental and clinical databases and charts. Multivariable logistic regression model was used to identify risk factors and stratify patients into high-risk and low-risk groups. A novel ORN classification system was developed to depict ORN severity …

Utility Of Whole Slide Imaging For Intraoperative Consultation: Experience Of A Large Academic Center, Ahmed Shehabeldin, Prih Rohra, Linton D Sellen, Jianping Zhao, Doaa Alqaidy, Hermineh Aramin, Nadia Hameed, Ydamis Estrella Perez, Zongshan Lai, Yi Tat Tong, Denái R Milton, Mary E Edgerton, Gregory Fuller, Donna Hansel, Victor G Prieto, Leomar Y Ballester, Phyu P Aung

Faculty, Staff and Student Publications

Context.—: In the United States, review of digital whole slide images (WSIs) using specific systems is approved for primary diagnosis but has not been implemented for intraoperative consultation.

Objective.—: To evaluate the safety of review of WSIs and compare the efficiency of review of WSIs and glass slides (GSs) for intraoperative consultation.

Design.—: Ninety-one cases previously submitted for frozen section evaluation were randomly selected from 8 different anatomic pathology subspecialties. GSs from these cases were scanned on a Leica Aperio AT2 scanner at ×20 magnification (0.25 μm/pixel). The slides were deidentified, and a short relevant clinical history was provided for …

Dyadic Yoga For Head And Neck Cancer Patients Undergoing Chemoradiation And Their Family Caregivers, Kathrin Milbury, David I Rosenthal, Yisheng Li, An Thuy Ngo-Huang, Smitha Mallaiah, Sania Yousuf, Clifton D Fuller, Carol Lewis, Eduardo Bruera, Lorenzo Cohen

Faculty, Staff and Student Publications

Objectives: Concurrent chemoradiation to treat head and neck cancer (HNC) may result in debilitating toxicities. Targeted exercise such as yoga therapy may buffer against treatment-related sequelae; thus, this pilot RCT examined the feasibility and preliminary efficacy of a yoga intervention. Because family caregivers report low caregiving efficacy and elevated levels of distress, we included them in this trial as active study participants.

Methods: HNC patients and their caregivers were randomized to a 15-session dyadic yoga program or a waitlist control (WLC) group. Prior to randomization, patients completed standard symptom (MDASI-HN) and patients and caregivers completed quality of life (SF-36) assessments. …

Prospective Performance Of The Iwg-2023 Criteria And Ipss-M In A Phase 2 Trial Of Guadecitabine For Higher-Risk Mds Or Cmml, Samuel Urrutia, Prithviraj Bose, Yesid Alvarado, Gautam Borthakur, Farhad Ravandi, Naval Daver, Naveen Pemmaraju, Elias Jabbour, Koichi Takahashi, Tapan Kadia, Courtney Dinardo, Steven Kornblau, Rashmi Kanagal-Shamanna, Xuelin Huang, Kristy Bodden, Hagop Kantarjian, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Guadecitabine (SGI-110) is a dinucleotide form of decitabine that has been studied in myelodysplastic syndrome (MDS) and acute myeloid leukemia. Here, we present the results of a single-center phase 2 trial of this agent for patients with higher-risk MDS or chronic myelomonocytic leukemia (CMML). Guadecitabine was administered at a dose of 60 mg/m2 subcutaneously for 5 days. Of 100 enrolled patients, 82% had MDS. The median age was 69 years, and International Prognostic Scoring System (IPSS) was intermediate-2 in 78% and high in 14%. Thirty-eight percent had complex cytogenetics, and 32% had TP53 mut . By the International Working Group …

Automated Spontaneous Echo Contrast Detection Using A Multisequence Attention Convolutional Neural Network, Ouwen Huang, Zewei Shi, Naveen Garg, Corey Jensen, Mark L Palmeri

Faculty, Staff and Student Publications

OBJECTIVE: Spontaneous echo contrast (SEC) is a vascular ultrasound finding associated with increased thromboembolism risk. However, identification requires expert determination and clinician time to report. We developed a deep learning model that can automatically identify SEC. Our model can be applied retrospectively without deviating from routine clinical practice. The retrospective nature of our model means future works could scan archival data to opportunistically correlate SEC findings with documented clinical outcomes.

METHODS: We curated a data set of 801 archival acquisitions along the femoral vein from 201 patients. We used a multisequence convolutional neural network (CNN) with ResNetv2 backbone and visualized …

Diagnostic And Prognostic Biomarkers Of Chronic Pancreatitis: A Conceptual Framework Based On The Probe Design, Dhiraj Yadav, Darwin L Conwell, Stephen J Pandol, Hanno Steen, Ziding Feng, Liang Li

Faculty, Staff and Student Publications

No abstract provided.

Dietary Fiber And Gut Bacteria Shape Infection Susceptibility, Aqsa Mohammed, Robert R Jenq

Faculty, Staff and Student Publications

Gut microbiota composition has been reported to affect pathogen susceptibility but its specific effects, the underlying mechanisms and the potential influence of the diet remain unexplored. In their recent study, Desai and colleagues (Wolter et al, 2024), explore the complex interaction between diet, the gut microbiota and pathogen susceptibility, highlighting a diet-dependent role of the mucin-degrading microbe Akkermansia muciniphila.

Predictive Capacity Of Immune-Related Adverse Events And Cytokine Profiling In Neoadjuvant Immune Checkpoint Inhibitor Trials For Head And Neck Squamous Cell Carcinoma\, Angela E Alnemri, Sruti Tekumalla, Annie E Moroco, Ioannis Vathiotis, Madalina Tuluc, Stacey Gargano, Tingting Zhan, David M Cognetti, Joseph M Curry, Athanassios Argiris, Alban Linnenbach, Andrew P South, Larry A Harshyne, Jennifer M Johnson, Adam J Luginbuhl

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OBJECTIVES: Certain low-level immune-related adverse events (irAEs) have been associated with survival benefits in patients with various solid tumors on immune checkpoint inhibitors (ICIs). We aimed to investigate the association between irAEs and response to neoadjuvant ICIs in patients with head and neck squamous cell carcinoma (HNSCC) and to identify differences in circulating cytokine levels based on irAE status.

METHODS: This was a retrospective cohort study including three neoadjuvant clinical trials from July 2017 to January 2022: NCT03238365 (nivolumab ± tadalafil), NCT03854032 (nivolumab ± BMS986205), NCT03618654 (durvalumab ± metformin). The presence and type of irAEs, pathologic treatment response, and survival …

Stmnd1 Is A Phylogenetically Ancient Stathmin Which Localizes To Motile Cilia And Exhibits Nuclear Translocation That Is Inhibited When Soluble Tubulin Concentration Increases, Xiang Deng, Bryan O Seguinot, Gary Bradshaw, Jong Suk Lee, Shannon Coy, Marian Kalocsay, Sandro Santagata, Timothy Mitchison

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Stathmins are small, unstructured proteins that bind tubulin dimers and are implicated in several human diseases, but whose function remains unknown. We characterized a new stathmin, STMND1 (Stathmin Domain Containing 1) as the human representative of an ancient subfamily. STMND1 features a N-terminal myristoylated and palmitoylated motif which directs it to membranes and a tubulin-binding stathmin-like domain (SLD) that contains an internal nuclear localization signal. Biochemistry and proximity labeling showed that STMND1 binds tubulin, and live imaging showed that tubulin binding inhibits translocation from cellular membranes to the nucleus. STMND1 is highly expressed in multiciliated epithelial cells, where it localizes …

A Bayesian Quasi-Likelihood Design For Identifying The Minimum Effective Dose And Maximum Utility Dose In Dose-Ranging Studies, Feng Tian, Ruitao Lin, Li Wang, Ying Yuan

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Most existing dose-ranging study designs focus on assessing the dose-efficacy relationship and identifying the minimum effective dose. There is an increasing interest in optimizing the dose based on the benefit-risk tradeoff. We propose a Bayesian quasi-likelihood dose-ranging design that jointly considers safety and efficacy to simultaneously identify the minimum effective dose and the maximum utility dose to optimize the benefit-risk tradeoff. The binary toxicity endpoint is modeled using a beta-binomial model. The efficacy endpoint is modeled using the quasi-likelihood approach to accommodate various types of data (e.g. binary, ordinal or continuous) without imposing any parametric assumptions on the dose-response curve. …