Digital Commons Network^™

The Burden Of Burnout: Understanding Its Prevalence And Organizational Drivers In Medical Physics, Deborah Schofield, C Lynn Chevalier, Laurence Court, William Harmsen, Akiva Turner

Faculty, Staff and Student Publications

Background: Burnout is a work-related syndrome characterized by increased levels of emotional exhaustion (EE) and depersonalization (DP) along with decreased levels of personal achievement. In the healthcare setting, higher burnout levels have been associated with negative impacts on personnel, an increased risk of errors, and a decrease in the quality of delivered care.

Purpose: The purpose of this study was to assess the prevalence of burnout among medical physicists working in the United States. Additionally, the impact of personal and organizational features on burnout risk was examined.

Methods: The anonymous survey was distributed to 1962 full members of the American …

A Plain Language Summary Of Polaris: A Study To Look At Different Doses Of Encorafenib Plus Binimetinib For People With Braf V600-Mutant Melanoma With Brain Metastasis, Alexander M Menzies, Georgina V Long, Amiee Kohn, Hussein Tawbi, Jeffrey Webe, Keith Flaherty, Grant A Mcarthur, Paolo A Ascierto, Yanina Pfluger, Karl Lewis, Katy K Tsai, Omid Hamid, Hans Prenen, Luis Fein, Erjian Wang, Carolin Guenzel, Fan Zhang, Joseph F Kleh, Alessandra Di Pietro, Michael A Davies

Faculty, Staff and Student Publications

What is this summary about?People with a type of melanoma called advanced or metastatic BRAF V600- mutant melanoma, with a change in the BRAF gene, that has spread to the brain have poor outcomes.Current treatments include encorafenib (BRAFTOVI®) and binimetinib (MEKTOVI®). The POLARIS clinical study looked at whether increasing the encorafenib dose would make treatment more effective, with similar side effects, in these patients.The first part of the study, known as the safety lead-in, looked at the side effects of a high dose of encorafenib together with binimetinib. This was followed by a phase 2 part to …

Advancing The Development Of Trip13 Inhibitors: A High-Throughput Screening Approach, Rae M Sammons, Soma Ghosh, Lacin Yapindi, Eun Jeong Cho, Faye M Johnson, Kevin N Dalby

Faculty, Staff and Student Publications

TRIP13, a promising target for cancer therapy, has been identified as a key regulator of the mitotic checkpoint. Overexpression of TRIP13 is associated with poor clinical outcomes in various cancers. Inhibition of TRIP13 has the potential to address therapeutic challenges in cancer, particularly in therapy-resistant and Rb-deficient cancers. Despite the potential therapeutic benefits of TRIP13 inhibition, the development of TRIP13 inhibitors has been hindered by the lack of a robust high-throughput screening (HTS) assay. We developed a luminescence-based biochemical assay for TRIP13 activity to address this challenge using the ADP-Glo detection system. This assay offers high sensitivity, low background signal, …

Cross-Institutional Dental Electronic Health Record Entity Extraction Via Generative Artificial Intelligence And Synthetic Notes, Yao-Shun Chuang, Chun-Teh Lee, Guo-Hao Lin, Ryan Brandon, Xiaoqian Jiang, Muhammad F Walji, Oluwabunmi Tokede

Faculty, Staff and Student Publications

Background: While most health-care providers now use electronic health records (EHRs) to document clinical care, many still treat them as digital versions of paper records. As a result, documentation often remains unstructured, with free-text entries in progress notes. This limits the potential for secondary use and analysis, as machine-learning and data analysis algorithms are more effective with structured data.

Objective: This study aims to use advanced artificial intelligence (AI) and natural language processing (NLP) techniques to improve diagnostic information extraction from clinical notes in a periodontal use case. By automating this process, the study seeks to reduce missing data in …

Implementation Of An Opt-Out And Rapid Point-Of-Care Syphilis Testing Program For Pregnant Patients Presenting To The Emergency Department, Irene Stafford, Carrie Bakunas, Joe Haydamous, Ana Mosqueda, Jeffrey D Klausner, Leandro Mena, Sean C Blackwell

Faculty, Staff and Student Publications

Background: Adult and congenital syphilis rates are rising in the United States. The aim of this pre- and post-implementation study was to determine whether implementation of an opt-out laboratory-based and rapid syphilis point-of-care testing program in the emergency department (ED) improves the detection and treatment of syphilis during pregnancy in a high-prevalence region.

Methods: This pre- and post-implementation study was conducted at the University of Texas Health Science Center, Houston, TX. During the pre-implementation phase (November 1, 2023-February 29, 2024), pregnant patients presenting to the ED underwent laboratory-based syphilis testing using the reverse algorithm only when clinically indicated. In the …

Implementation Mapping To Guide Adoption Of A Semi-Structured Intraoperative Anesthesia Handoff Tool, Aubrey Samost-Williams, Reed Richter, Naveen Vanga, Spandana Mandaloju, Adlai Arandela, Srikanth Sridhar, Eric J Thomas

Faculty, Staff and Student Publications

There frequently exists a gap between known best practices and real-world methods. Closing this gap involves thoughtful implementation, typically involving multiple implementation strategies. Implementation mapping is a technique that links the innovation being implemented with potential barriers to implementation and connects these barriers to the strategies that form the implementation plan. This study demonstrates the application of implementation mapping to guide the adoption of the Epic Health Systems Intraoperative Anesthesia Handoff Report. The objective is to create a comprehensive implementation plan tailored to the anticipated challenges of the local environment. There are five steps in implementation mapping: (1) performing a …

Is There An Association Between Inflammatory Biomarkers And Organ Space Surgical Site Infection After Emergency Laparotomy In Massively Transfused Trauma Patients?, Stephanie Martinez Ugarte, Mokunfayo O Fajemisin, Chelsea J Guy-Frank, James M Klugh, Xu Zhang, Erin E Fox, Charles E Wade, Kimberly A Mankiewicz, Lillian S Kao

Faculty, Staff and Student Publications

Background: The relationship between inflammatory biomarkers (IB) and organ space surgical site infections (OS-SSIs) after emergency laparotomy (EL) is poorly understood.

Methods: Retrospective, single-center analysis of patients in the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial who underwent EL and survived 48 h after admission was performed. IB levels of IL-6, IL-8, G-CSF, MCP-1, neutrophil to lymphocyte ratio, and platelet to lymphocyte ratio were analyzed. IB and OS-SSIs association was evaluated using the Wilcoxon rank sum test.

Results: Of 74 eligible patients, 80 % were male, 69 % sustained blunt trauma, the injury severity score was 31 (24-41), …

The Macrophage Sterol Transport Protein Orp2 Promotes Cholesterol Efflux And Prevents Foam Cell Formation And Atherosclerosis, Xiaowei Wang, Kenan Peng, Yudi Zhao, Liwen Qiu, Chenxi Liang, Yaqian Dou, Qianqian Dong, Xiaoting Ma, Jinye Tang, Yidan Ma, Lin Liu, Mingqi Zheng, Hongyuan Yang, Mingming Gao

Faculty, Staff and Student Publications

Cholesterol-loaded macrophage foam cells are a key feature of atherosclerotic plaques. Oxysterol-binding protein-related protein 2 (ORP2) facilitates the transport of cholesterol from lysosomes to the plasma membrane in cultured cell lines. However, the role of ORP2 in macrophages and its involvement in atherosclerosis remain unclear. In this study, we found ORP2 expression was reduced in atherosclerotic vessels and in macrophages exposed to oxidized LDL (ox-LDL). Myeloid-specific human ORP2 overexpression (hORP2MOE) mice were generated and crossed with atherosclerotic-prone ApoE−/− mice and then fed a high-fat diet (HFD) to induce atherosclerosis. Our results showed that myeloid-specific hORP2 overexpression significantly reduced the atherosclerotic …

Time To Weight Plateau With Tirzepatide Treatment In The Surmount-1 And Surmount-4 Clinical Trials, Deborah B Horn, Scott Kahan, Rachel L Batterham, Dachuang Cao, Clare J Lee, Madhumita Murphy, Sylvia Gonsahn-Bollie, Farai Chigutsa, Adam Stefanski, Julia P Dunn

Faculty, Staff and Student Publications

The rate of weight reduction during obesity treatment declines over time and eventually reaches a weight plateau. We investigated factors associated with time to weight plateau (TTWP) in tirzepatide-treated participants with obesity or overweight in a post-hoc analysis of SURMOUNT-1 and SURMOUNT-4 trials. Participants adherent to tirzepatide treatment and achieving ≥5% weight loss by primary endpoint (week 72 SURMOUNT-1; week 88 SURMOUNT-4) were included. Weight plateau was defined as a weight change < 5% over a 12-week interval and all subsequent 12-week intervals. TTWP was time from randomization to the start of the first 12-week interval. Association between baseline characteristics and TTWP was assessed. Overall, 1438 participants in SURMOUNT-1 and 259 in SURMOUNT-4 were included. Across BMI categories (overweight, class I, II, and III), median TTWP in SURMOUNT-1 was 24.3, 26.0, 36.1, and 36.1 weeks, respectively (p < .05, class II and III vs. overweight). By week 72, 90.2%, 88.9%, 87.6%, and 87.8% of participants in SURMOUNT-1 had reached a weight plateau across respective BMI categories [Correction added on 22 January 2025, after first online publication: The "72%" has been changed to "72" in this version.]. Higher doses of tirzepatide (10/15 mg), younger age, and female sex were more likely to reach a weight plateau later. Results in SURMOUNT-4 were similar. In this post-hoc analysis, most participants reached a weight plateau by week 72. Higher doses of tirzepatide, younger age, and female sex were associated with a longer TTWP. Further research into modifiers of weight reduction phases with tirzepatide may inform treatment decisions for its use in chronic weight management. Clinical Trial Registration: ClinicalTrials.gov, identifiers NCT04184622 (SURMOUNT-1) and NCT04660643 (SURMOUNT-4), available at http://www.clinicaltrials.gov/.

Enhancing Seizure Control In Ultra-Refractory Postencephalitic Epilepsies Using Multinodal Network Neuromodulation, Subhiksha Srinivasan, Surya Suresh, Ganne Chaitanya, Manoj Saranathan, Nitin Tandon, Sandipan Pati

Faculty, Staff and Student Publications

This case series reports the formidable challenge posed by postencephalitic epilepsies, characterized by frequent drug-resistant seizures and neuropsychiatric and cognitive comorbidities. Polypharmacy is frequently required, and surgical resection may not be feasible due to multifocality. Neuromodulation therapies, including Deep Brain Stimulation (DBS) and Responsive Neurostimulation (RNS), offer a potential lifeline. In this case series, we shed light on the intricate landscape of seizure management and neuropsychiatric comorbidities in five individuals with frequent seizures (often weekly) and ultra-refractory epilepsy (defined as resistance to more than six different antiseizure medications, including failed epilepsy surgery) following catastrophic encephalitis. Four out of five patients …

Expanding The Clinical Spectrum Of Porokeratosis Ptychotropica, Brooke R Bartley, Dylan R Maldonado, Steven Mays, Ronald P Rapini

Faculty, Staff and Student Publications

Porokeratosis ptychotropica (PP) is a rare variant of porokeratosis, typically presenting as pink to brown hyperkeratotic plaques in the gluteal cleft and buttocks, defined histologically by multiple cornoid lamellae. Diagnosis of PP is challenging due to its clinical overlap with other dermatologic conditions and inconsistent terminology in the literature. This case report describes a 47-year-old woman exhibiting clinical and pathological features of PP but with a more diffuse presentation than previously documented. The case emphasizes the diagnostic complexities of PP, particularly in atypical presentations, and highlights the critical role of histological examination in distinguishing it from other porokeratoses.

Ao Spine Clinical Practice Recommendations For Diagnosis And Management Of Degenerative Cervical Myelopathy: Evidence Based Decision Making - A Review Of Cutting Edge Recent Literature Related To Degenerative Cervical Myelopathy, Michael G Fehlings, Nathan Evaniew, Paula Valerie Ter Wengel, Aditya Vedantam, Daipayan Guha, Konstantinos Margetis, Aria Nouri, Aminul I Ahmed, Chris J Neal, Benjamin M Davies, Mario Ganau, Jefferson R Wilson, Allan R Martin, Lukas Grassner, Lindsay Tetreault, Vafa Rahimi-Movaghar, Rex Marco, James Harrop, James Guest, Mohammed Ali Alvi, Karlo M Pedro, Brian K Kwon, Charles G Fisher, Shekar N Kurpad

Faculty, Staff and Student Publications

Study Design

Literature review of key topics related to degenerative cervical myelopathy (DCM) with critical appraisal and clinical recommendations.

Objective

This article summarizes several key current topics related to the management of DCM.

Methods

Recent literature related to the management of DCM was reviewed. Four articles were selected and critically appraised. Recommendations were graded as Strong or Conditional.

Results

Article 1: The Relationship Between pre-operative MRI Signal Intensity and outcomes. Conditional recommendation to use diffusion-weighted imaging MR signal changes in the cervical cord to evaluate prognosis following surgical intervention for DCM. Article 2: Efficacy and Safety of Surgery for Mild …

Fracture Patterns In Craniofacial Gunshot Wounds: A Seven-Year Experience, Gabriela G Cruz, Sameer H Siddiqui, David Z Allen, Kunal R Shetty, Sean P Mckee, Brady J Anderson, Mark Knackstedt, W Katherine Kao, Tang Ho

Faculty, Staff and Student Publications

Objective: To characterize facial fracture patterns and understand predictors of surgical repair and LOS with the objective of assisting providers in managing and understanding these complex injuries.

Study design: This is a retrospective cohort chart review study.

Methods: A retrospective review was conducted for patients admitted with gunshot wounds (GSWs) to the head, neck, or face between January 2013 and March 2020 at a level one trauma tertiary care hospital. Univariate and multivariate analysis were performed to identify associations with surgical repair and LOS.

Results: Of the 578 patients with head, neck, or facial GSWs, 204 survived and sustained facial …

New Frontiers: The Intern Experience In A Newly Established Integrated Plastic Surgery Program, Hendrik Lintel, Imran Rizvi, Michael Haydon, Erik S Marques, Matthew R Greives, Mohin A Bhadkamkar

Faculty, Staff and Student Publications

The plastic surgery residency pathway has undergone many changes since its inception. The advent of integrated training has largely taken over as the predominant residency model with the addition of a few new programs every year. There is currently a paucity of literature describing the experiences of first-year interns in a new integrated residency program transitioning from the independent model. In this article, we seek to elucidate some of the advantages and difficulties encountered by the initial residents of a newly established integrated program and the steps taken to pave the way for future matched integrated trainees.

Assessment Of Contextualized Reinforcement Pathology In A Community Sample Of Young Adult Substance Users, Ángel García-Pérez, Alba González-Roz, Roberto Secades-Villa, Gema Aonso-Diego, Sara Weidberg, Jin H Yoon

Faculty, Staff and Student Publications

Background: Alcohol, tobacco, and cannabis are the most commonly used substances among young populations, often leading to polysubstance use, which correlates with problematic consumption and adverse health outcomes. The contextualized reinforcer pathology (CRP) model explains addictive behaviors through several constructs, including the following: drug demand, delay discounting (DD), and substance-free and substance-related reinforcement. Most previous studies have focused on a single CRP construct and the couse of only two substances. This study aimed to characterize three subgroups of young adults reporting past month use of alcohol only, alcohol + tobacco or cannabis, and alcohol + tobacco + cannabis, in terms …

Pharmacogenetics Of Plasma Dolutegravir Exposure During 1-Month Rifapentine/Isoniazid Treatment Of Latent Tuberculosis, Nia Covington, Anne F Luetkemeyer, Marjorie Z Imperial, Rodney Dawson, Yoninah Cramer, Sue Rosenkranz, Susan Swindells, Irina Gelmanova, Anchalee Avihingsanon, Roberto C Arduino, Wadzanai Samaneka, Kelly E Dooley, Rada Savic, Anthony T Podany, David W Haas

Faculty, Staff and Student Publications

In Advancing Clinical Therapeutics Globally protocol A5372, a pharmacokinetic study of dolutegravir with 1-month of daily rifapentine/isoniazid, twice-daily dolutegravir offset the induction effects of rifapentine on plasma dolutegravir trough concentrations (C trough ). Here, we characterize the impact on dolutegravir C trough of UGT1A1 , AADAC , and NAT2 polymorphisms that affect dolutegravir, rifapentine, and isoniazid, respectively. People with HIV receiving dolutegravir-based antiretroviral therapy with an indication to treat latent tuberculosis underwent pharmacokinetic sampling during dolutegravir 50 mg once daily alone, and on day 28 of dolutegravir 50 mg twice daily with rifapentine/isoniazid. Multivariable linear regression models characterized genetic associations …

Three-Dimensional Printed Models To Accelerate Resident Surgical Learning Curve For Standard Endoscopic Sinus Surgery Techniques, Jumah G Ahmad, Alexander J Citardi, Amber U Luong, William C Yao

Faculty, Staff and Student Publications

Background: Endoscopic sinus surgery presents significant visuospatial challenges to surgical trainees. We tested the utility of novel 3D printed models to simulate sinus surgery tasks to improve endoscopic skillsets in resident trainees.

Methods: This was a prospective quality improvement study of 10 ENT residents (PGY1-5). Participants rotated through 4 stations with different 3D simulation training modules designed to enhance endoscopic skillsets in the axial, sagittal and coronal planes (e.g., straight forceps to grasp a bead from a ledge, angled instruments to cannulate openings). Participants completed a self-assessment survey on the subjective sinus surgical skills using a visual analog …

Placenta Accreta Spectrum, Present And Future: The Eunice Kennedy Shriver National Institute Of Child Health And Human Development Workshop Summary, Christina M Duzyj, Brett D Einerson, Yalda Afshar, Karin A Fox, Antonio F Saad, Daniela A Carusi, Christina L Herrera, Deirdre J Lyell, Alfred Z Abuhamad, Michaela K Farber, Anne C Roberts, Sebastian R Hobson, Loic Sentilhes, Baha M Sibai, Koji Matsuo, Kristen Terlizzi, Scott A Shainker, Robert M Silver, Helena C Bartels, Thomas D Shipp, Marilyn Huang, Alison G Cahill, Jason D Wright, George R Saade, Monica Longo

Faculty, Staff and Student Publications

Placenta accreta spectrum (PAS) disorder poses significant risks to maternal health, given the complexities of screening, diagnosis, and management. To address these challenges, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) hosted a workshop on June 10-11, 2024, bringing together expert health care professionals, researchers, stakeholders, and patient advocates to identify knowledge gaps, with an overarching goal of informing future research and best practices for PAS. Key discussions revolved around the resources and infrastructure needed to advance screening, diagnosis, and clinical management of PAS, alongside ways to enhance collaboration across disciplines. Participants considered strategies to …

Psychometrics Of Inflammatory Back Pain Criteria In The Us Population, Mark C Hwang, Seokhun Kim, Shervin Assassi, Alexis Ogdie, Michael H Weisman, John Reveille, Charles Green

Faculty, Staff and Student Publications

Objectives: Evaluation of axial spondyloarthritis relies on capturing various inflammatory back pain (IBP) features represented in different criteria. These criteria are likely to be interpreted differently across demographic subpopulations. We examined IBP criteria dimensionality and differential item functioning (DIF) among different age, gender, and race groups using a nationally representative sample.

Methods: We utilised the National Health and Nutrition Examination Survey (NHANES) 2009-2010 dataset, a US nationally representative data collection with demographic weighting. The Arthritis Questionnaire (ARQ) within NHANES included questions from published Calin, European Spondyloarthropathy Study Group, and Berlin criteria (8a and 7b). Confirmatory factor analysis (CFA) was performed …

Design Of Conquest, A Novel, Randomized, Placebo-Controlled, Phase 2b Platform Clinical Trial To Investigate New Treatments For Patients With Early Active Systemic Sclerosis With Interstitial Lung Disease, Dinesh Khanna, Luke B Evnin, Shervin Assassi, Wade W Benton, Gregory Gordon, Karina Maslova, Juergen Steffgen, Toby M Maher

Faculty, Staff and Student Publications

Objective: Safe, effective therapies are urgently needed for patients with systemic sclerosis. However, clinical trial recruitment is challenging given the limited number of people with systemic sclerosis and further restrictions imposed by eligibility criteria. Innovative approaches are needed to accelerate development of new therapies. This article describes the rationale and trial design for CONQUEST (NCT06195072), a novel platform clinical trial sponsored by the Scleroderma Research Foundation, a not-for-profit organization.

Methods: CONQUEST is a multicentre, double-blind, randomized, placebo-controlled, Phase 2b platform trial evaluating the efficacy, safety and pharmacodynamics of multiple investigational products to treat early active systemic sclerosis with …

Perceptions Of The Intensity Of Heart Failure Medications Among Hospitalized Older Adults: A Pilot Qualitative Study, Nuzha A Amjad, Saeed Shoar, Catherine Bryant, Meghan Hunt, Min Ji Kwak

Faculty, Staff and Student Publications

Background: Guidelines for heart failure (HF) management recommend high target doses for medications. These targets are based on standardized dosing regimens that rarely consider the complex challenges faced by older patients. However, little is known about such challenges perceived by older adults. We assessed older adults' perceived challenges with HF medication utilization, which may guide a more patient-centered definition of the target intensity for HF medications.

Methods: We conducted a pilot qualitative study using one-on-one, semi-structured interviews with older adults. We included patients over the age of 65 years admitted to the acute cardiac care units (cardiac intensive care unit …

One Cutoff Is Not Enough: Assessing Different Area Deprivation Index Cutoffs For Insurance Types On Surgical Desirability Of Outcome Ranking (Door), Susanne Schmidt, Michael A Jacobs, Daniel E Hall, Karyn B Stitzenberg, Lillian S Kao, Bradley B Brimhall, Chen-Pin Wang, Laura S Manuel, Hoah-Der Su, Jonathan C Silverstein, Paula K Shireman

Faculty, Staff and Student Publications

Background: Social Determinants of Health impact health outcomes. Area Deprivation Index (ADI) is used to risk-adjust for neighborhood affluence/deprivation but guidance on choosing deprivation cutoffs is lacking. We hypothesize that different ADI cutoffs are required for different insurance types.

Methods: National Surgical Quality Improvement Program data 2013-2019 merged with electronic health records from three academic healthcare systems. Desirability of Outcome Ranking (DOOR) assessed the association of ADI cutoffs for different insurance types, adjusted for operative stress, frailty, and case status (elective, urgent, emergent). Secondary analyses assessed the association of ADI with case status.

Results: Patients with Private insurance living in …

A Virtual Wellness Program To Enhance Well-Being For Pediatric Oncology Staff During The Covid-19 Pandemic, Karen M Moody, Maria Chang Swartz, Zachary Gresham, Martha Askins, Laura Cahalan, Christine Geistkemper, Amy Heaton, Ruitao Lin, Melissa Melo, Alakh Rajan, Madeline Smith, Priti Tewari, Keyana Williams, Cheng-Han Yang, Rhonda Robert

Faculty, Staff and Student Publications

In response to the COVID-19 global health crisis and mandated social isolation, Pediatric leadership at MD Anderson Children's Cancer Hospital was concerned for the psychological impact on its workforce and encouraged wellness programming. A grassroots wellness taskforce was assembled for the Division of Pediatrics. The task force's primary mission was to promote the well-being of clinicians and non-clinical staff members through a broadly accessible, sustainable, and effective virtual wellness program. Guided by the Stanford Model for Professional Fulfillment, a virtual program entitled, "Weekly Wellness Webex" for Pediatrics staff was launched. Weekly Wellness Webex is a 1-hour live-streamed program with varied …

International Expert-Based Consensus Definition, Classification Criteria, And Minimum Data Elements For Osteoradionecrosis Of The Jaw: An Interdisciplinary Modified Delphi Study, Amy C Moreno, Erin E Watson, Laia Humbert-Vidan, Douglas E Peterson, Lisanne V Van Dijk, Teresa Guerrero Urbano, Lisa Van Den Bosch, Andrew J Hope, Matthew S Katz, Frank J P Hoebers, Ruth A Aponte Wesson, James E Bates, Paolo Bossi, Adeyinka F Dayo, Mélanie Doré, Eduardo Rodrigues Fregnani, Thomas J Galloway, Daphna Y Gelblum, Issa A Hanna, Christina E Henson, Sudarat Kiat-Amnuay, Anke Korfage, Nancy Y Lee, Carol M Lewis, Charlotte Duch Lynggaard, Antti A Mäkitie, Marco Magalhaes, Yvonne M Mowery, Carles Muñoz-Montplet, Jeffrey N Myers, Ester Orlandi, Jaymit Patel, Jillian M Rigert, Deborah Saunders, Jonathan D Schoenfeld, Ugur Selek, Efsun Somay, Vinita Takiar, Juliette Thariat, Gerda M Verduijn, Alessandro Villa, Nicholas S West, Max J H Witjes, Alex M Won, Mark E Wong, Christopher M K L Yao, Simon W Young, Kamal Al-Eryani, Carly E A Barbon, Doke J M Buurman, François J Dieleman, Theresa M Hofstede, Abdul Ahad Khan, Adegbenga O Otun, John C Robinson, Lauren Hum, Jorgen Johansen, Rajesh Lalla, Alexander Lin, Vinod Patel, Richard J Shaw, Mark S Chambers, Daniel Ma, Mabi Singh, Noam Yarom, Abdallah Sherif Radwan Mohamed, Katherine A Hutcheson, Stephen Y Lai, Clifton David Fuller

Faculty, Staff and Student Publications

Purpose: Osteoradionecrosis of the jaw (ORNJ) is a severe iatrogenic disease characterized by bone death after radiation therapy to the head and neck. With >9 published definitions and at least 16 classification systems, the true incidence and severity of ORNJ are obscured by lack of a standard for disease definition and severity assessment, leading to inaccurate estimation of incidence, reporting ambiguity, and likely underdiagnosis worldwide. This study aimed to achieve consensus on an explicit definition and phenotype of ORNJ and related precursor states through data standardization to facilitate effective diagnosis, monitoring, and multidisciplinary management of ORNJ.

Methods and materials: The …

Implications Of Omitting Sentinel Lymph Node Biopsy On Adjuvant Decision Making For Patients With Small Breast Cancers, Kerollos Nashat Wanis, Melissa P Mitchell, Sharon H Giordano, Jennifer Keating Litton, Simona F Shaitelman, Nina Tamirisa, Isabelle Bedrosian, Wenli Dong, Yu Shen, Kelly K Hunt, Puneet Singh, Susie X Sun, Abigail S Caudle, Henry M Kuerer, Funda Meric-Bernstam, Rosa F Hwang, Taiwo Adesoye

Faculty, Staff and Student Publications

Background: Selective omission of sentinel lymph node biopsy (SLNB) in patients with early breast cancer limits surgical morbidity. Adoption of this strategy relies on multidisciplinary consensus. Understanding how SLNB omission influences guideline-based adjuvant treatment decisions, and the proportion of patients impacted, can help guide decision-making.

Patients and methods: Data from the National Cancer Database (2018-2020) was used to estimate the proportions of patients with cT1N0 hormone receptor-positive breast cancer for whom adjuvant chemotherapy, CDK4/6 inhibitor therapy, and regional nodal irradiation decisions would be impacted by the absence of lymph node pathology if national treatment guidelines were followed. Because OncotypeDX score …

Therapeutic Hurdles In Acute Myeloid Leukemia: Leukemic Stem Cells, Inflammation And Immune Dysfunction, Bofei Wang, Patrick K Reville, Hussein A Abbas

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) is an aggressive and highly heterogeneous hematological malignancy characterized by clonal expansion and differentiation arrest in myeloid progenitor cells. Despite advancements in chemotherapy, allogeneic hematopoietic stem cell transplantation, and post-remission maintenance therapies, the long-term survival remains unsatisfactory with high rates of relapse and refractory. These therapeutic challenges are mediated by multiple factors, including the complexity of the cellular hierarchies in AML, the interaction of leukemic stem cells (LSCs) with the bone marrow niche, inflammation, and immune evasion mechanisms. Further, the absence of specific surface markers that distinguish LSCs from normal hematopoietic stem cells, together with LSCs' …

Trem2 Depletion In Pancreatic Cancer Elicits Pathogenic Inflammation And Accelerates Tumor Progression Via Enriching Il-1Β+ Macrophages, Daowei Yang, Xinlei Sun, Hua Wang, Ignacio I Wistuba, Huamin Wang, Anirban Maitra, Yang Chen

Faculty, Staff and Student Publications

Background & aims: Pancreatic ductal adenocarcinoma (PDAC) has a complex tumor microenvironment enriched with tumor-associated macrophages. Triggering receptor expressed on myeloid cells 2 (TREM2) is highly expressed by a subset of macrophages in PDAC. However, the functional role of TREM2 in PDAC progression remains elusive.

Methods: We generated a novel transgenic mouse model (KPPC;Trem2-/-) that enables the genetic depletion of TREM2 in the context of spontaneous PDAC development. Single-cell RNA-sequencing analysis was used to identify changes in the tumor immune microenvironment on TREM2 depletion. We evaluated the impacts of TREM2 depletion on the tumor immune microenvironment to elucidate the functions …

Gut Microbiota In Immuno-Oncology: A Practical Guide For Medical Oncologists With A Focus On Antibiotics Stewardship, Arielle Elkrief, Bertrand Routy, Lisa Derosa, Laura Bolte, Jennifer A Wargo, Jennifer L Mcquade, Laurence Zitvogel

Faculty, Staff and Student Publications

The gut microbiota has emerged as a critical determinant of immune checkpoint inhibitor (ICI) efficacy, resistance, and toxicity. Retrospective and prospective studies profiling the taxonomic composition of intestinal microbes of patients treated with ICI have revealed specific gut microbial signatures associated with response. By contrast, dysbiosis, which can be caused by chronic inflammatory processes (such as cancer) or comedications, is a risk factor of resistance to ICI. Recent large-scale meta-analyses have confirmed that antibiotic (ATB) use before or during ICI therapy alters the microbiota repertoire and significantly shortens overall survival, even after adjusting for prognostic factors. These results underscore the …

A Gut-On-A-Chip Incorporating Human Faecal Samples And Peristalsis Predicts Responses To Immune Checkpoint Inhibitors For Melanoma, Mattia Ballerini, Serena Galiè, Punit Tyagi, Carlotta Catozzi, Hariam Raji, Amir Nabinejad, Angeli D G Macandog, Alessandro Cordiale, Bianca Ionela Slivinschi, Karol K Kugiejko, Martina Freisa, Paola Occhetta, Jennifer A Wargo, Pier F Ferrucci, Emilia Cocorocchio, Nicola Segata, Andrea Vignati, Andrey Morgun, Michela Deleidi, Teresa Manzo, Marco Rasponi, Luigi Nezi

Faculty, Staff and Student Publications

Patient responses to immune checkpoint inhibitors can be influenced by the gastrointestinal microbiome. Mouse models can be used to study microbiome-host crosstalk, yet their utility is constrained by substantial anatomical, functional, immunological and microbial differences between mice and humans. Here we show that a gut-on-a-chip system mimicking the architecture and functionality of the human intestine by including faecal microbiome and peristaltic-like movements recapitulates microbiome-host interactions and predicts responses to immune checkpoint inhibitors in patients with melanoma. The system is composed of a vascular channel seeded with human microvascular endothelial cells and an intestinal channel with intestinal organoids derived from human …

Cll Cell-Derived Exosomes Alter The Immune And Hematopoietic Systems, Ivo Veletic, David M Harris, Uri Rozovski, Maria Teresa S Bertilaccio, George A Calin, Koichi Takahashi, Ping Li, Zhiming Liu, Taghi Manshouri, Rares-Constantin Drula, Ken Furudate, Muharrem Muftuoglu, Anwar Hossain, William G Wierda, Michael J Keating, Zeev Estrov

Faculty, Staff and Student Publications

The origins of immunosuppression, neutropenia, and anemia in patients with chronic lymphocytic leukemia (CLL) are not fully understood. Because in patients with CLL, circulating exosomes, which participate in cell-to-cell interactions, are CLL cell-derived, we examined whether those exosomes contribute to abnormal features of this disease. Our data revealed that CLL cell-derived exosomes engulfed by healthy donors’ monocytes, fibrocytes, and lymphocytes altered target-cell gene and protein expression and suppressed normal hematopoiesis. CLL cell-derived exosomes increased normal monocytes’ CD14 and CD16 expression such that it mimicked the accessory cell profile and upregulated T cells’ checkpoint PD-1 and CD160 protein levels, potentially reducing …