Medical Specialties Commons^™

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

Faculty, Staff and Student Publications

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

Faculty, Staff and Student Publications

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

Faculty, Staff and Student Publications

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. …

Adaptive Bayesian Information Borrowing Methods For Finding And Optimizing Subgroup-Specific Doses, Jingyi Zhang, Ruitao Lin, Xin Chen, Fangrong Yan

Faculty, Staff and Student Publications

In precision oncology, integrating multiple cancer patient subgroups into a single master protocol allows for the simultaneous assessment of treatment effects in these subgroups and promotes the sharing of information between them, ultimately reducing sample sizes and costs and enhancing scientific validity. However, the safety and efficacy of these therapies may vary across different subgroups, resulting in heterogeneous outcomes. Therefore, identifying subgroup-specific optimal doses in early-phase clinical trials is crucial for the development of future trials. In this article, we review various innovative Bayesian information-borrowing strategies that aim to determine and optimize subgroup-specific doses. Specifically, we discuss Bayesian hierarchical modeling, …

Salpingectomy For Ovarian Cancer Prevention: Video Education For The Surgeon, Emily Macarthur, Kara Long Roche, Joseph Sakran, Sunil H Patel, Peter Najjar, Karen H Lu, Megan Gornet, Anja S Frost, Meghan Walrath, Tom Bauer, Gyyong Oh, Rebecca Stone

Faculty, Staff and Student Publications

Given the unremitting obstacles to effectively screen for and treat ovarian cancer (OC), prevention is a necessary countermeasure. The recent discovery of the fallopian tube as the origin of the most common and deadly type of OC, high grade serous cancer (HGSC), makes prevention through salpingectomy possible (Madsen et al., 2015). Opportunistic salpingectomy (OS) is the practice of removing the post-reproductive fallopian tubes at the time of other intraperitoneal surgery, or for sterilization in lieu of tubal ligation, to decrease OC risk (Falconer et al., 2015). The safety, effectiveness, and reach of OS as a primary prevention strategy depends on …

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 …

Hypofractionated Radiotherapy For Glioblastoma: A Large Institutional Retrospective Assessment Of 2 Approaches, Thomas H Beckham, Michael K Rooney, Mary F Mcaleer, Amol J Ghia, Martin C Tom, Subha Perni, Susan Mcgovern, David Grosshans, Caroline Chung, Chenyang Wang, Brain De, Todd Swanson, Arnold Paulino, Wen Jiang, Sherise Ferguson, Chirag B Patel, Jing Li, Debra N Yeboa

Faculty, Staff and Student Publications

Background: Glioblastoma (GBM) poses therapeutic challenges due to its aggressive nature, particularly for patients with poor functional status and/or advanced disease. Hypofractionated radiotherapy (RT) regimens have demonstrated comparable disease outcomes for this population while allowing treatment to be completed more quickly. Here, we report our institutional outcomes of patients treated with 2 hypofractionated RT regimens: 40 Gy/15fx (3w-RT) and 50 Gy/20fx (4w-RT).

Methods: A single-institution retrospective analysis was conducted of 127 GBM patients who underwent 3w-RT or 4w-RT. Patient characteristics, treatment regimens, and outcomes were analyzed. Univariate and multivariable Cox regression models were used to estimate progression-free survival (PFS) and …

Development Of An Antioxidant-Rich Sugar-Free Plantain Candy And Assessment Of Its Shelf Life In A Flexible Laminate, Poulami Sarkar, Paramita Bhattacharjee, Bidhan Das

Faculty, Staff and Student Publications

RESEARCH BACKGROUND: Candy is a popular confection worldwide, and it would be beneficial to society if it were converted into a source of antioxidant molecules to eliminate its adverse health effects. The amount of antioxidants available even in fruit candies is questionable due to the high thermal processing losses they undergo and the presence of various food additives. Plantains (

EXPERIMENTAL APPROACH: To accomplish the first objective, lyophilized plantain powder, sorbitol and mannitol were used as base materials with minimal additives under minimal processing conditions to reduce processing loss. Sensory, proximate, physicochemical and phytochemical properties, including the antioxidant synergy among …

Trends In Shortages Of Lead Chelators From 2001 To 2022, James D Whitledge, Pelayia Soto, Kieran M Glowacki, Diane P Calello, Erin R Fox, Maryann Mazer-Amirshahi

Faculty, Staff and Student Publications

OBJECTIVE: The study aims to describe drug shortages affecting lead chelators in the United States from 2001 through 2022.

METHODS: Drug shortage data were retrieved from the University of Utah Drug Information Service from January 1, 2001, through December 31, 2022. Shortages of first- and second-line lead chelators were analyzed. Drug class, formulation, administration route, shortage reason, shortage duration, generic status, single-source status, and presence of temporally overlapping shortages were examined. Total shortage months, percentages of study period on shortage, and median shortage durations were calculated.

RESULTS: Thirteen lead chelator shortages were reported during the study period. Median duration was …

Preventative Treatment Of Tuberous Sclerosis Complex With Sirolimus: Phase I Safety And Efficacy Results, Jamie K Capal, David M Ritter, David Neal Franz, Molly Griffith, Kristn Currans, Bridget Kent, E Martina Bebin, Hope Northrup, Mary Kay Koenig, Tomoyuki Mizuno, Alexander A Vinks, Stephanie L Galandi, Wujuan Zhang, Kenneth D R Setchell, Kelly M Kremer, Carlos M Prada, Hansel M Greiner, Katherine Holland-Bouley, Paul S Horn, Darcy A Krueger

Faculty, Staff and Student Publications

Objective: Tuberous sclerosis complex (TSC) results from overactivity of the mechanistic target of rapamycin (mTOR). Sirolimus and everolimus are mTOR inhibitors that treat most facets of TSC but are understudied in infants. We sought to understand the safety and potential efficacy of preventative sirolimus in infants with TSC.

Methods: We conducted a phase 1 clinical trial of sirolimus, treating five patients until 12 months of age. Enrolled infants had to be younger than 6 months of age with no history of seizures and no clinical indication for sirolimus treatment. Adverse events (AEs), tolerability, and blood concentrations of sirolimus measured by …

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 …

Open Tibial Shaft Fracture Fixation Strategies: Intramedullary Nailing, External Fixation, And Plating, Michelle Shen, Nirmal Tejwani

Faculty, Staff and Student Publications

Tibial shaft fractures are one of the most common orthopaedic injuries. Open tibial shaft fractures are relatively common because of the paucity of soft tissue surrounding the bone. Despite the prevalence of these injuries, the optimal fixation strategy is still a topic of debate. The purpose of this article was to review the current literature on open tibial shaft fracture fixation strategies including intramedullary nailing, external fixation, and plating.

Insurance Coverage During Transitions: Evidence From Medicaid Automatic Enrollment For Children Receiving Supplemental Security Income, Stephanie Rennane, Danielle Sobol, Bradley D Stein, Andrew Dick

Faculty, Staff and Student Publications

OBJECTIVES: To analyze relationships between Medicaid automatic enrollment for child Supplemental Security Income (SSI) recipients and health insurance coverage during transitions.

DATA SOURCES AND STUDY SETTING: Medical Expenditure Panel Study, 2000-2020 and National Survey for Children with Special Health Care Needs, 2001-2010.

STUDY DESIGN: Leveraging variation in SSI-Medicaid automatic enrollment status across regions and over time, we estimate a regression model to quantify associations between automatic enrollment and insurance coverage. We validate our findings in the NS-CSHCN.

DATA COLLECTION: Our sample includes children receiving SSI for a disability. We also analyze a subsample of children newly enrolled in SSI.

PRINCIPAL …

The Unusual Substrate Specificity Of Escherichia Coli Cardiolipin Synthase C Does Not Require The Product Of The Transcriptionally Engaged Ymdb Gene, Katsuhiro Sawasato, Mikhail Bogdanov

Faculty, Staff and Student Publications

Polycistronic transcription and translation of ymdB-clsC have been thought to be required for full activity of ClsC. The authentic initiation codon of the clsC gene is present within the open reading frame of the upstream located ymdB gene. ClsC translated from authentic initiation codon drives cardiolipin (CL) synthesis without transcriptionally paired YmdB. YmdB is not necessary for the substrate specificity of ClsC utilizing phosphatidylethanolamine (PE) as a co-substrate.

Common Epilepsy Variants From The General Population Are Not Associated With Epilepsy Among Individuals With Tuberous Sclerosis Complex, Melissa A Richard, Philip J Lupo, Erik A Ehli, Mustafa Sahin, Darcy A Krueger, Joyce Y Wu, Elizabeth M Bebin, Kit Sing Au, Hope Northrup, Laura S Farach

Faculty, Staff and Student Publications

Common genetic variants identified in the general population have been found to increase phenotypic risks among individuals with certain genetic conditions. Up to 90% of individuals with tuberous sclerosis complex (TSC) are affected by some type of epilepsy, yet the common variants contributing to epilepsy risk in the general population have not been evaluated in the context of TSC-associated epilepsy. Such knowledge is important to help uncover the underlying pathogenesis of epilepsy in TSC which is not fully understood, and critical as uncontrolled epilepsy is a major problem in this population. To evaluate common genetic modifiers of epilepsy, our study …

Incidence And Factors In Delayed Neurological Deficits After Subarachnoid Hemorrhage In Mice, William Wroe, Ari Dienel, Sungha Hong, Kanako Matsumura, Jose Guzman, Kiara Torres, Angelica Bernal, Hussein A Zeineddine, Peeyush Thankamani Pandit, Spiros L Blackburn, Devin W Mcbride

Faculty, Staff and Student Publications

Background: Delayed cerebral ischemia (DCI) is one of the most feared complications in aneurysmal subarachnoid hemorrhage (SAH). Animal models are crucial to studying the disease mechanisms and potential treatments. DCI in rodents was thought to not exist; herein we examine literature and our experience with DCI in rodents.

Methods: Daily behavioral performance was assessed every day from day 1 to up to 7 days post-SAH on mice from 5 different studies that used the endovascular perforation model. Performance was graded using an 8-test sensorimotor neuroscore previously described. The daily neuroscore was then used to identify the incidence and timing of …

Management Of Aortoesophageal Fistula Primarily Using Esophageal Preservation, Alexander Mills, Akiko Tanaka, Ashley Dawson, Robert Hetz, Holly Smith, Michael Lopez, Hazim Safi, Anthony Estrera

Faculty, Staff and Student Publications

Objective: Aortoesophageal fistula is a rare, life-threatening condition. There is no consensus regarding the surgical management of the esophagus in this condition.

Methods: We retrospectively evaluated 13 patients diagnosed with aortoesophageal fistulas at a single institution from 2003 to 2021. Descriptive statistics were used to analyze patient characteristics, operative characteristics, and patient outcomes. Kaplan-Meier survival analysis was performed.

Results: Patients' mean age was 63.5 years, and 6 (46.2%) were female. The most common presenting symptoms were hemoptysis/hematemesis (69.2%), chest/back pain (46.2%), and fever (38.5%). Twelve patients (92.3%) had a history of aortic procedures. The median time between the index operation …

Adverse Pregnancy Outcomes And Long-Term Mortality In Women, Casey Crump, Jan Sundquist, Kristina Sundquist

Faculty, Staff and Student Publications

Importance: Women with adverse pregnancy outcomes, such as preterm delivery or preeclampsia, have higher future risks of cardiometabolic disorders; however, little is known about their long-term mortality risks. A better understanding of such risks is needed to facilitate early identification of high-risk women and preventive actions.

Objective: To determine long-term mortality risks associated with 5 major adverse pregnancy outcomes in a large population-based cohort of women.

Design, setting, and participants: This national cohort study in Sweden used the Swedish Medical Birth Register, containing prenatal and birth information for nearly all deliveries in Sweden since 1973, to identify women who had …

Sociodemographic And Patient Reported Outcomes By Racial And Ethnicity Status Among Participants In A Randomized Controlled Trial For Methamphetamine Use Disorder, Chukwuemeka N Okafor, Thomas Carmody, Angela L Stotts, Gavin Bart, Taryn L Mayes, Tara Karns-Wright, Madhukar Trivedi, Steve Shoptaw, Jennifer S Potter

Faculty, Staff and Student Publications

Background: There has been a significant increase in methamphetamine use and methamphetamine use disorder (Meth UD) in the United States, with evolving racial and ethnic differences.

Objectives: This secondary analysis explored racial and ethnic differences in baseline sociodemographic and clinical characteristics as well as treatment effects on a measure of substance use recovery, depression symptoms, and methamphetamine craving among participants in a pharmacotherapy trial for Meth UD.

Methods: The ADAPT-2 trial (ClinicalTrials.gov number, NCT03078075; N=403; 69% male) was a multisite, 12-week randomized, double-blind, trial that employed a two-stage sequential parallel design to evaluate the efficacy of combination naltrexone (NTX) …

A Prospective Observational Study Of Disease Severity And Mortality In Hispanic American Patients With Systemic Sclerosis, Bochra Jandali, Marka Lyons, Julio Charles, Meng Zhang, Samuel Theodore, Claudia Pedroza, Maureen D Mayes, Shervin Assassi

Faculty, Staff and Student Publications

Objective: To characterize disease manifestations in Hispanic American patients with systemic sclerosis (SSc) in comparison with non-Hispanic White and Black patients.

Methods: Longitudinal clinical characteristics were collected prospectively in the Genetics versus Environment in Scleroderma Outcome Study cohort. All patients fulfilled the classification criteria for SSc and had a disease duration less than five years at enrollment.

Results: A cohort of 427 patients, consisting of 124 Hispanic, 220 non-Hispanic White, and 83 non-Hispanic Black participants were examined. At enrollment, Hispanic patients were significantly younger but had longer disease duration, higher frequency of U1-RNP positivity as well as concurrent systemic lupus …

Incidence And Clinical Outcomes Of Perforations During Mechanical Thrombectomy For Medium Vessel Occlusion In Acute Ischemic Stroke: A Retrospective, Multicenter, And Multinational Study, Adam A Dmytriw, Basel Musmar, Hamza Salim, Sherief Ghozy, James E Siegler, Hassan Kobeissi, Hamza Shaikh, Jane Khalife, Mohamad Abdalkader, Piers Klein, Thanh N Nguyen, Jeremy J Heit, Robert W Regenhardt, Nicole M Cancelliere, Joshua D Bernstock, Kareem El Naamani, Abdelaziz Amllay, Lukas Meyer, Anne Dusart, Flavio Bellante, Géraud Forestier, Aymeric Rouchaud, Suzana Saleme, Charbel Mounayer, Jens Fiehler, Anna Luisa Kühn, Ajit S Puri, Christian Dyzmann, Peter T Kan, Marco Colasurdo, Gaultier Marnat, Jérôme Berge, Xavier Barreau, Igor Sibon, Simona Nedelcu, Nils Henninger, Thomas R Marotta, Christopher J Stapleton, James D Rabinov, Takahiro Ota, Shogo Dofuku, Leonard Ll Yeo, Benjamin Yq Tan, Anil Gopinathan, Juan Carlos Martinez-Gutierrez, Sergio Salazar-Marioni, Sunil Sheth, Leonardo Renieri, Carolina Capirossi, Ashkan Mowla, Lina Chervak, Achala Vagal, Nimer Adeeb, Hugo H Cuellar-Saenz, Stavropoula I Tjoumakaris, Pascal Jabbour, Priyank Khandelwal, Arundhati Biswas, Frédéric Clarençon, Mahmoud Elhorany, Kevin Premat, Iacopo Valente, Alessandro Pedicelli, João Pedro Filipe, Ricardo Varela, Miguel Quintero-Consuegra, Nestor R Gonzalez, Markus A Möhlenbruch, Jessica Jesser, Vincent Costalat, Adrien Ter Schiphorst, Vivek Yedavalli, Pablo Harker, Yasmin Aziz, Benjamin Gory, Christian Paul Stracke, Constantin Hecker, Ramanathan Kadirvel, Monika Killer-Oberpfalzer, Christoph J Griessenauer, Ajith J Thomas, Cheng-Yang Hsieh, David S Liebeskind, Răzvan Alexandru Radu, Andrea M Alexandre, Illario Tancredi, Tobias D Faizy, Robert Fahed, Charlotte Weyland, Boris Lubicz, Aman B Patel, Vitor Mendes Pereira, Adrien Guenego, Mad-Mt Consortium

Faculty, Staff and Student Publications

Background: Mechanical thrombectomy (MT) has revolutionized the treatment of acute ischemic stroke (AIS) due to large vessel occlusion (LVO), but its efficacy and safety in medium vessel occlusion (MeVO) remain less explored. This multicenter, retrospective study aims to investigate the incidence and clinical outcomes of vessel perforations (confirmed by extravasation during an angiographic series) during MT for AIS caused by MeVO.

Methods: Data were collected from 37 academic centers across North America, Asia, and Europe between September 2017 and July 2021. A total of 1373 AIS patients with MeVO underwent MT. Baseline characteristics, procedural details, and clinical outcomes were analyzed. …

Endovascular Treatment Of Acute Ischemic Stroke Patients With Tandem Lesions: Antegrade Versus Retrograde Approach, Milagros Galecio-Castillo, Michael Abraham, Mudassir Farooqui, Ameer E Hassan, Afshin A Divani, Mouhammad A Jumaa, Marc Ribo, Nils Petersen, Johanna Fifi, Waldo R Guerrero, Amer M Malik, James E Siegler, Thanh N Nguyen, Sunil A Sheth, Albert J Yoo, Guillermo Linares, Nazli Janjua, Darko Quispe-Orozco, Abid Qureshi, Wondwossen G Tekle, Asad Ikram, Syed F Zaidi, Cynthia B Zevallos, Belen Taborda, Alex Devarajan, Linda Zhang, Mohamad Abdalkader, Sergio Salazar-Marioni, Jazba Soomro, Weston Gordon, Aaron Rodriguez-Calienes, Juan Vivanco-Suarez, Katrina Woolfolk, Maxim Mokin, Dileep R Yavagal, Santiago Ortega-Gutierrez

Faculty, Staff and Student Publications

Objective: The optimal technique for treating tandem lesions (TLs) with endovascular therapy is debatable. The authors evaluated the functional, safety, and procedural outcomes of different approaches in a multicenter study.

Methods: Anterior circulation TL patients treated from January 2015 to December 2020 were divided on the basis of antegrade versus retrograde approach and included. The evaluated outcomes were favorable modified Rankin Scale (mRS) score (mRS score 0-2) at 3 months, ordinal shift in mRS score, successful recanalization, excellent recanalization, first-pass effect (FPE), time from groin puncture to successful recanalization, symptomatic intracranial hemorrhage (sICH), and 90-day mortality.

Results: Among 691 patients …

Low-Dose Immune Tolerance Induction For Severe Hemophilia A Inhibitor Patients: Immunosuppressants Are Generally Not Necessary For Inhibitor-Titer Below 200 Bu/Ml, Zhengping Li, Jie Sun, Zekun Li, Zhenping Chen, Guoqing Liu, Wanru Yao, Xiaoling Cheng, Gang Li, Yingzi Zhen, Di Ai, Yaohan Zhou, Qianqian Mao, Man-Chiu Poon, Runhui Wu

Faculty, Staff and Student Publications

Importance

It remained unclear that the efficacy comparison between low‐dose immune tolerance induction (LD‐ITI) incorporating immunosuppressants (IS) when severe hemophilia A (SHA) patients had inhibitor‐titer ≥200 Bethesda Units (BU)/mL (LD‐ITI‐IS200 regimen) and LD‐ITI combining with IS when SHA patients had inhibitor‐titer ≥40 BU/mL (LD‐ITI‐IS40 regimen).

Objective

To compare the efficacy of the LD‐ITI‐IS200 regimen with that of the LD‐ITI‐IS40 regimen for SHA patients with high‐titer inhibitors.

Methods

A prospective cohort study on patients receiving LD‐ITI‐IS200 compared to those receiving LD‐ITI‐IS40 from January 2021 to December 2023. Both received LD‐ITI [FVIII 50 IU/kg every other day]. IS (rituximab + prednisone) was …

Loss Of Ovol2 In Triple-Negative Breast Cancer Promotes Fatty Acid Oxidation Fueling Stemness Characteristics, Ruipeng Lu, Jingjing Hong, Tong Fu, Yu Zhu, Ruiqi Tong, Di Ai, Shuai Wang, Qingsong Huang, Ceshi Chen, Zhiming Zhang, Rui Zhang, Huiling Guo, Boan Li

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, has a poor prognosis and lacks effective treatment strategies. Here, the study discovered that TNBC shows a decreased expression of epithelial transcription factor ovo-like 2 (OVOL2). The loss of OVOL2 promotes fatty acid oxidation (FAO), providing additional energy and NADPH to sustain stemness characteristics, including sphere-forming capacity and tumor initiation. Mechanistically, OVOL2 not only suppressed STAT3 phosphorylation by directly inhibiting JAK transcription but also recruited histone deacetylase 1 (HDAC1) to STAT3, thereby reducing the transcriptional activation of downstream genes carnitine palmitoyltransferase1 (CPT1A and CPT1B). PyVT-Ovol2 knockout mice develop a …

Comparative Analysis Of Brain Language Templates With Primary Language Areas Detected From Presurgical Fmri Of Brain Tumor Patients, Jina Lee, Vinodh A Kumar, Jian Ming Teo, Rami W Eldaya, Ping Hou, Kyle R Noll, Sherise D Ferguson, Sujit S Prabhu, Ho-Ling Liu

Faculty, Staff and Student Publications

INTRODUCTION: Functional brain templates are often used in the analysis of clinical functional MRI (fMRI) studies. However, these templates are mostly built based on anatomy or fMRI of healthy subjects, which have not been fully vetted in clinical cohorts. Our aim was to evaluate language templates by comparing with primary language areas (PLAs) detected from presurgical fMRI of brain tumor patients.

METHODS: Four language templates (A-D) based on anatomy, task-based fMRI, resting-state fMRI, and meta-analysis, respectively, were compared with PLAs detected by fMRI with word generation and sentence completion paradigms. For each template, the fraction of PLA activations enclosed by …

Stat5b Mutations In Myeloid Neoplasms Differ By Disease Subtypes But Characterize A Subset Of Chronic Myeloid Neoplasms With Eosinophilia And/Or Basophilia, C Cameron Yin, Wayne Tam, Serena M Walker, Amandeep Kaur, Madhu M Ouseph, Wei Xie, Olga K Weinberg, Peng Li, Zhuang Zuo, Mark J Routbort, Simon Chen, L Jeffrey Medeiros, Tracy I George, Attilio Orazi, Daniel A Arber, Adam Bagg, Robert P Hasserjian, Sa A Wang

Faculty, Staff and Student Publications

STAT5B has been reported as a recurrent mutation in myeloid neoplasms with eosinophilia, but its overall frequency and importance across a spectrum of myeloid neoplasms are largely unknown. We conducted a multicenter study on a series of 82 myeloid neoplasms with STAT5B mutations detected by next-generation sequencing. The estimated frequency of STAT5B mutations in myeloid neoplasms was low, <0.5%, but mutations were detected in all categories of such neoplasms, including myelodysplastic syndrome (MDS, 28%), acute myeloid leukemia (AML, 26%), myelodysplastic/myeloproliferative neoplasm (MDS/MPN, 18%), Philadelphia chromosome-negative classic MPN (12%), systemic mastocytosis (1%), and, with a notably high frequency, chronic eosinophilic leukemia, not otherwise specified (CEL-NOS, 15%). STAT5B mutations occurred preferentially in the SH2 domain (95%), involved 12 different codons, with the N642H hotspot being the most common (78%). Co-mutations were present in all cases and clonal hierarchy analysis showed that STAT5B mutations tended to be subclonal in AML, MPN, and MDS, but frequently dominant/co-dominant in CEL-NOS (83%), followed by MDS/MPN (40%). Across the group, eosinophilia and/or basophilia were common (41%), frequently observed in cases in which STAT5B mutations were detected at initial diagnosis (P<0.0001), with a high variant allele frequency (median 42.5%, P=0.0001), as a dominant/ co-dominant clone (P<0.0001), involving the canonical N642H (P=0.0607), and associated with fewer co-mutations (P=0.0009). Our data show that the characteristics and importance of a STAT5B mutation differ among myeloid neoplasms, but if present as a dominant mutation and detected at initial diagnosis, it appears to be a driver mutation in a subgroup of chronic myeloid neoplasms, preferentially promoting a proliferation of eosinophils and basophils.

Statistical And Practical Considerations In Planning And Conduct Of Dose-Optimization Trials, Ying Yuan, Heng Zhou, Suyu Liu

Faculty, Staff and Student Publications

The U.S. Food and Drug Administration launched Project Optimus with the aim of shifting the paradigm of dose-finding and selection toward identifying the optimal biological dose that offers the best balance between benefit and risk, rather than the maximum tolerated dose. However, achieving dose optimization is a challenging task that involves a variety of factors and is considerably more complicated than identifying the maximum tolerated dose, both in terms of design and implementation. This article provides a comprehensive review of various design strategies for dose-optimization trials, including phase 1/2 and 2/3 designs, and highlights their respective advantages and disadvantages. In …

Excess Risk Of Chronic Health Conditions In Hispanic Survivors Of Adolescent And Young Adult Cancers, Amy M Berkman, Eunju Choi, John M Salsman, Susan K Peterson, Christabel K Cheung, Clark R Andersen, Qian Lu, J A Livingston, Michelle A T Hildebrandt, Susan K Parsons, Michael E Roth

Faculty, Staff and Student Publications

Purpose: There is a growing population of survivors of adolescent and young adult (AYA) cancers (age 15-39 years at diagnosis). Studies in AYA cancer survivors have identified racial and ethnic disparities in long-term outcomes. To understand the extent to which a cancer diagnosis exacerbates pre-existent health disparities within a minoritized population, comparisons should be made to those of the same race or ethnicity without a cancer history.

Methods: Self-reported data from the National Health Interview Survey (2009-2018) were used to identify Hispanic AYA cancer survivors and Hispanic age- and sex-matched controls. SES factors (marital status, income, education, insurance) and prevalence …

The Association Of Nursing Homes' Organizational Context With Care Aide Empowerment: A Cross-Sectional Study, Alba Iaconi, Matthias Hoben, Whitney Berta Phd, Yinfei Duan, Peter G Norton, Yuting Song, Stephanie A Chamberlain, Anna Beeber, Ruth A Anderson, Holly J Lanham, Janelle Perez, Jing Wang, Katharina Choroschun, Shovana Shrestha, Greta Cummings, Carole A Estabrooks

Faculty, Staff and Student Publications

Background and objectives: Organizational context is thought to influence whether care aides feel empowered, but we lack empirical evidence in the nursing home sector. Our objective was to examine the association of features of nursing homes' unit organizational context with care aides' psychological empowerment.

Research design and methods: This cross-sectional study analyzed survey data from 3765 care aides in 91 Western Canadian nursing homes. Random-intercept mixed-effects regressions were used to examine the associations between nursing home unit organizational context and care aides' psychological empowerment, controlling for care aide, care unit, and nursing home covariates.

Results: Organizational (IVs) culture, social capital, …