Medical Specialties Commons^™

Germline Genetic Testing And Survival Outcomes Among Children With Rhabdomyosarcoma: A Report From The Children's Oncology Group, Bailey A Martin-Giacalone, He Li, Michael E Scheurer, Dana L Casey, Shannon Dugan-Perez, Deborah A Marquez-Do, Donna Muzny, Richard A Gibbs, Donald A Barkauskas, David Hall, Douglas R Stewart, Joshua D Schiffman, Matthew T Mcevoy, Javed Khan, David Malkin, Corinne M Linardic, Brian D Crompton, Jack F Shern, Stephen X Skapek, Rajkumar Venkatramani, Douglas S Hawkins, Aniko Sabo, Sharon E Plon, Philip J Lupo

Faculty, Staff and Students Publications

IMPORTANCE: Determining the impact of germline cancer-predisposition variants (CPVs) on outcomes could inform novel approaches to testing and treating children with rhabdomyosarcoma.

OBJECTIVE: To assess whether CPVs are associated with outcome among children with rhabdomyosarcoma.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, data were obtained for individuals, aged 0.01-23.23 years, newly diagnosed with rhabdomyosarcoma who were treated across 171 Children's Oncology Group sites from March 15, 1999, to December 8, 2017. Data analysis was performed from June 16, 2021, to May 15, 2023.

EXPOSURE: The presence of a CPV in 24 rhabdomyosarcoma-associated cancer-predisposition genes (CPGs) or an expanded set …

Congenital Tooth Agenesis And Risk Of Early-Onset Cancer, Saga Elise Eiset, Jeremy Schraw, Gitte Vrelits Sørensen, Pernille Axél Gregersen, Sonja A Rasmussen, Cecilia H Ramlau-Hansen, Philip J Lupo, Henrik Hasle

Faculty, Staff and Students Publications

IMPORTANCE: There is some evidence that tooth agenesis (congenital absence of 1 or more teeth) is associated with cancer risk, especially carcinomas of the colon and ovaries, but results of previous studies are conflicting, and associations have not yet been evaluated in a population-based setting.

OBJECTIVE: To examine the association between tooth agenesis and specific cancer types before 40 years of age.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study used linking data from nationwide registries in Denmark to assess all Danish live-born singletons born from January 1, 1977, to December 31, 2018, and followed up for up to 40 …

Intraoperative Evaluation Of Breast Tissues During Breast Cancer Operations Using The Masspec Pen, Kyana Y Garza, Mary E King, Chandandeep Nagi, Rachel J Dehoog, Jialing Zhang, Marta Sans, Anna Krieger, Clara L Feider, Alena V Bensussan, Michael F Keating, John Q Lin, Min Woo Sun, Robert Tibshirani, Christopher Pirko, Kirtan A Brahmbhatt, Ahmed R Al-Fartosi, Alastair M Thompson, Elizabeth Bonefas, James Suliburk, Stacey A Carter, Livia S Eberlin

Faculty, Staff and Students Publications

IMPORTANCE: Surgery with complete tumor resection remains the main treatment option for patients with breast cancer. Yet, current technologies are limited in providing accurate assessment of breast tissue in vivo, warranting development of new technologies for surgical guidance.

OBJECTIVE: To evaluate the performance of the MasSpec Pen for accurate intraoperative assessment of breast tissues and surgical margins based on metabolic and lipid information.

DESIGN, SETTING, AND PARTICIPANTS: In this diagnostic study conducted between February 23, 2017, and August 19, 2021, the mass spectrometry-based device was used to analyze healthy breast and invasive ductal carcinoma (IDC) banked tissue samples from adult …

A Greb1-Steroid Receptor Feedforward Mechanism Governs Differential Greb1 Action In Endometrial Function And Endometriosis, Sangappa B Chadchan, Pooja Popli, Zian Liao, Eryk Andreas, Michelle Dias, Tianyuan Wang, Stephanie J Gunderson, Patricia T Jimenez, Denise G Lanza, Rainer B Lanz, Charles E Foulds, Diana Monsivais, Francesco J Demayo, Hari Krishna Yalamanchili, Emily S Jungheim, Jason D Heaney, John P Lydon, Kelle H Moley, Bert W O'Malley, Ramakrishna Kommagani

Faculty, Staff and Students Publications

Cellular responses to the steroid hormones, estrogen (E2), and progesterone (P4) are governed by their cognate receptor's transcriptional output. However, the feed-forward mechanisms that shape cell-type-specific transcriptional fulcrums for steroid receptors are unidentified. Herein, we found that a common feed-forward mechanism between GREB1 and steroid receptors regulates the differential effect of GREB1 on steroid hormones in a physiological or pathological context. In physiological (receptive) endometrium, GREB1 controls P4-responses in uterine stroma, affecting endometrial receptivity and decidualization, while not affecting E2-mediated epithelial proliferation. Of mechanism, progesterone-induced GREB1 physically interacts with the progesterone receptor, acting as a cofactor in a positive feedback …

Safety Of Ambulatory Surgery For Obstructive Sleep Apnea: A Retrospective Review, Dylan Gregory Bertoni, Emily Garvey, Neha Garg, Dev Amin, Sruti Tekumalla, Derek Mann, Bita Naimi, Tingting Zhan, Patrick Hunt, Maurits Boon, Colin Huntley

Jefferson Hospital Staff Papers and Presentations

OBJECTIVE: Assess the safety of ambulatory surgery performed for obstructive sleep apnea.

STUDY DESIGN: Retrospective chart review.

SETTING: Tertiary care hospital.

METHODS: Demographic data including age, gender, race, body mass index, insurance status, socioeconomic status, and distance traveled for surgery was collected, as well as comorbidities, and apnea-hypopnea index (AHI). Outcome variables included continuous positive airway pressure reinitiation, planned/unplanned postoperative admission, emergency department (ED) presentation, or readmission within 7 and 14 days of surgery.

RESULTS: A total of 601 patients were included, who underwent sleep surgery between 2017 and 2022. The median age was 55 years [interquartile range: 19]. A …

Incidental Ring-Hyperenhancing Liver Micronodules At Ct Hepatic Arteriography-Guided Percutaneous Thermal Ablation Of Colorectal Liver Metastases, Jessica Albuquerque, Yuan-Mao Lin, Iwan Paolucci, Caleb S O'Connor, Ching-Wei Tzeng, Jean-Nicolas Vauthey, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

CT during hepatic arteriography (CTHA) is a highly sensitive imaging method for detecting colorectal liver metastases (CLMs), which supports its use during percutaneous thermal liver ablation. In contrast to its high sensitivity, its specificity for incidental small CLMs not detected at preablation cross-sectional imaging is believed to be low given the absence of specific imaging signatures and the common presence of pseudolesions. In this retrospective study of 22 patients (mean age, 55 years ± 10.6 [SD]; 63.6% male, 36.4% female) with CLMs undergoing CTHA-guided microwave percutaneous thermal ablation between November 2017 and October 2022, the authors provided a definition of …

The Lymphoma Epidemiology Of Outcomes Cohort Study: Design, Baseline Characteristics, And Early Outcomes, James R Cerhan, Matthew J Maurer, Brian K Link, Andrew L Feldman, Thomas M Habermann, David L Jaye, W Richard Burack, Timothy J Mcdonnell, Francisco Vega, Jennifer R Chapman, Sergei Syrbu, Kiran R Vij, Giorgio Inghirami, John P Leonard, Leon Bernal-Mizrachi, Umar Farooq, Thomas E Witzig, George J Weiner, Yucai Wang, Juan P Alderuccio, Susan L Slager, Melissa C Larson, Shaun M Riska, Brianna J Gysbers, Julianne J Lunde, Tanner W Reicks, Amy A Ayers, Colin B O'Leary, Kathleen J Yost, Hongfang Liu, Grzegorz S Nowakowski, Jia Ruan, Dai Chihara, Jean L Koff, Carla Casulo, Carrie A Thompson, Jonathon B Cohen, Brad S Kahl, Loretta J Nastoupil, Izidore S Lossos, Jonathan W Friedberg, Peter Martin, Christopher R Flowers

Faculty, Staff and Student Publications

To address the current and long-term unmet health needs of the growing population of non-Hodgkin lymphoma (NHL) patients, we established the Lymphoma Epidemiology of Outcomes (LEO) cohort study (NCT02736357; https://leocohort.org/). A total of 7735 newly diagnosed patients aged 18 years and older with NHL were prospectively enrolled from 7/1/2015 to 5/31/2020 at 8 academic centers in the United States. The median age at diagnosis was 62 years (range, 18-99). Participants came from 49 US states and included 538 Black/African-Americans (AA), 822 Hispanics (regardless of race), 3386 women, 716 age <40 >years, and 1513 rural residents. At study baseline, we abstracted clinical, …

Normative Modelling Of Brain Morphometry Across The Lifespan With Centilebrain: Algorithm Benchmarking And Model Optimisation, Ruiyang Ge, Yuetong Yu, Yi Xuan Qi, Yu-Nan Fan, Shiyu Chen, Chuntong Gao, Shalaila S Haas, Faye New, Dorret I Boomsma, Henry Brodaty, Rachel M Brouwer, Randy Buckner, Xavier Caseras, Fabrice Crivello, Eveline A Crone, Susanne Erk, Simon E Fisher, Barbara Franke, David C Glahn, Udo Dannlowski, Dominik Grotegerd, Oliver Gruber, Hilleke E Hulshoff Pol, Gunter Schumann, Christian K Tamnes, Henrik Walter, Lara M Wierenga, Neda Jahanshad, Paul M Thompson, Sophia Frangou, Enigma Lifespan Working Group

Faculty, Staff and Student Publications

The value of normative models in research and clinical practice relies on their robustness and a systematic comparison of different modelling algorithms and parameters; however, this has not been done to date. We aimed to identify the optimal approach for normative modelling of brain morphometric data through systematic empirical benchmarking, by quantifying the accuracy of different algorithms and identifying parameters that optimised model performance. We developed this framework with regional morphometric data from 37 407 healthy individuals (53% female and 47% male; aged 3-90 years) from 87 datasets from Europe, Australia, the USA, South Africa, and east Asia following a …

Analysis Of East Asia Subgroup In Study 309/Keynote-775: Lenvatinib Plus Pembrolizumab Versus Treatment Of Physician's Choice Chemotherapy In Patients With Previously Treated Advanced Or Recurrent Endometrial Cancer, Kan Yonemori, Keiichi Fujiwara, Kosei Hasegawa, Mayu Yunokawa, Kimio Ushijima, Shiro Suzuki, Ayumi Shikama, Shinichiro Minobe, Tomoka Usami, Jae-Weon Kim, Byoung-Gie Kim, Peng-Hui Wang, Ting-Chang Chang, Keiko Yamamoto, Shirong Han, Jodi Mckenzie, Robert J Orlowski, Takuma Miura, Vicky Makker, Yong Man Kim

Faculty, Staff and Student Publications

OBJECTIVE: In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician's choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis.

METHODS: Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once …

The Hyphal-Specific Toxin Candidalysin Promotes Fungal Gut Commensalism, Shen-Huan Liang, Shabnam Sircaik, Joseph Dainis, Pallavi Kakade, Swathi Penumutchu, Liam D Mcdonough, Ying-Han Chen, Corey Frazer, Tim B Schille, Stefanie Allert, Osama Elshafee, Maria Hänel, Selene Mogavero, Shipra Vaishnava, Ken Cadwell, Peter Belenky, J Christian Perez, Bernhard Hube, Iuliana V Ene, Richard J Bennett

Faculty, Staff and Student Publications

The fungus Candida albicans frequently colonizes the human gastrointestinal tract, from which it can disseminate to cause systemic disease. This polymorphic species can transition between growing as single-celled yeast and as multicellular hyphae to adapt to its environment. The current dogma of C. albicans commensalism is that the yeast form is optimal for gut colonization, whereas hyphal cells are detrimental to colonization but critical for virulence

Artificial Intelligence-Based Radiotherapy Contouring And Planning To Improve Global Access To Cancer Care, Laurence E Court, Ajay Aggarwal, Anuja Jhingran, Komeela Naidoo, Tucker Netherton, Adenike Olanrewaju, Christine Peterson, Jeannette Parkes, Hannah Simonds, Christoph Trauernicht, Lifei Zhang, Beth M Beadle, Radiation Planning Assistant Consortium Collaborators, Affiliations Expand

Faculty, Staff and Student Publications

PURPOSE: Increased automation has been identified as one approach to improving global cancer care. The Radiation Planning Assistant (RPA) is a web-based tool offering automated radiotherapy (RT) contouring and planning to low-resource clinics. In this study, the RPA workflow and clinical acceptability were assessed by physicians around the world.

METHODS: The RPA output for 75 cases was reviewed by at least three physicians; 31 radiation oncologists at 16 institutions in six countries on five continents reviewed RPA contours and plans for clinical acceptability using a 5-point Likert scale.

RESULTS: For cervical cancer, RPA plans using bony landmarks were scored as …

Autoantibodies, Antigen-Autoantibody Complexes And Antigens Complement Ca125 For Early Detection Of Ovarian Cancer, Chae Young Han, Jacob S Bedia, Wei-Lei Yang, Sarah J Hawley, Lindsay Bergan, Marika Hopper, Joseph Celestino, Jing Guo, Terrie G Gornet, Antoninus Soosaipillai, Hailing Yang, Samantha D Doskocil, Anna E Lokshin, Beverly C Handy, Eleftherios P Diamandis, Richard G Moore, Karen H Lu, Zhen Lu, Karen S Anderson, Charles W Drescher, Steven J Skates, Robert C Bast

Faculty, Staff and Student Publications

BACKGROUND: Multiple antigens, autoantibodies (AAb), and antigen-autoantibody (Ag-AAb) complexes were compared for their ability to complement CA125 for early detection of ovarian cancer.

METHODS: Twenty six biomarkers were measured in a single panel of sera from women with early stage (I-II) ovarian cancers (n = 64), late stage (III-IV) ovarian cancers (186), benign pelvic masses (200) and from healthy controls (502), and then split randomly (50:50) into a training set to identify the most promising classifier and a validation set to compare its performance to CA125 alone.

RESULTS: Eight biomarkers detected ≥ 8% of early stage cases at 98% specificity. …

Plasma Ferritin Levels, Incident Heart Failure, And Cardiac Structure And Function: The Aric Study, Iman A F Aboelsaad, Brian L Claggett, Victoria Arthur, Pranav Dorbala, Kunihiro Matsushita, Brandon W Lennep, Bing Yu, Pamela L Lutsey, Chiadi E Ndumele, Youssef M K Farag, Amil M Shah, Leo F Buckley

Faculty, Staff and Student Publications

BACKGROUND: Whether iron deficiency contributes to incident heart failure (HF) and cardiac dysfunction has important implications given the prevalence of iron deficiency and the availability of several therapeutics for iron repletion.

OBJECTIVES: The aim of this study was to estimate the associations of plasma ferritin level with incident HF overall, HF phenotypes, and cardiac structure and function measures in older adults.

METHODS: Participants in the ongoing, longitudinal ARIC (Atherosclerosis Risk In Communities) study who were free of prevalent HF and anemia were studied. The associations of plasma ferritin levels with incident HF overall and heart failure with preserved ejection fraction …

Risk Of Alzheimer's Disease And Related Dementias In Persons With Glaucoma: A National Cohort Study, Casey Crump, Jan Sundquist, Weiva Sieh, Kristina Sundquist

Faculty, Staff and Student Publications

PURPOSE: Glaucoma is a heterogeneous group of optic neuropathies that potentially may be associated with other cerebral neurodegenerative processes leading to dementia. However, prior studies have been inconsistent. We examined dementia risks after glaucoma diagnosis in a large population-based cohort.

DESIGN: National matched cohort study.

PARTICIPANTS: A total of 324 730 persons diagnosed with glaucoma during 1995-2017 in Sweden and 3 247 300 age- and sex-matched population-based controls without prior dementia.

METHODS: Cox regression was used to compute hazard ratios (HRs) for Alzheimer's disease (AD), vascular dementia (VaD), and all-cause dementia in persons with glaucoma compared with controls, adjusting for …

Patients With Advanced Cancer And Their Spouses Parenting Minor Children: The Role Of The Relationship Context In Parenting Concerns, Kathrin Milbury, Sujin Ann-Yi, Morgan Jones, Yisheng Li, Meagan Whisenant, Sania Yousuf, Victoria Necroto, Mariana Chavez Mac Gregor, Eduardo Bruera

Faculty, Staff and Student Publications

Objective: Patients with advanced cancer who parent minor children report parenting concerns and increased psychological distress. This cross-sectional study seeks to understand parenting-related issues in patients and spousal caregivers from a relationship perspective.

Methods: Patients with a metastatic solid malignancy and their spouses independently completed cross-sectional assessments of psychological distress (Hospital Anxiety and Depression Scale), parenting concerns (Parenting Concern Questionnaire) and efficacy (Cancer-Related Parenting Self-Efficacy Scale), and relationship measures (DAS-7, Couples' Illness Communication Scale, and Family Relationship Index).

Results: Of the 51 patients (57% female, 49% NHW, mean age 42 years) and spouses (43% female, 43% NHW, mean age of …

Breastfeeding Initiation, Duration, And Associated Factors Among People With Hepatitis C Virus Infection, Jennifer L Grasch, Jessica A De Voest, George R Saade, Brenna L Hughes, Uma M Reddy, Maged M Costantine, Edward K Chien, Alan T N Tita, John M Thorp, Torri D Metz, Ronald J Wapner, Vishakha Sabharwal, Hyagriv N Simhan, Geeta K Swamy, Kent D Heyborne, Baha M Sibai, William A Grobman, Yasser Y El-Sayed, Brian M Casey, Samuel Parry, Eunice Kennedy Shriver National Institute Of Child Health And Human Development (Nichd) Maternal-Fetal Medicine Units (Mfmu) Network

Faculty, Staff and Student Publications

OBJECTIVE: To characterize breastfeeding behaviors and identify factors associated with breastfeeding initiation among people with hepatitis C virus (HCV) infection.

METHODS: We conducted a secondary analysis of a multicenter observational cohort of pregnant people with singleton gestations and HCV seropositivity. This analysis includes individuals with data on breastfeeding initiation and excludes those with human immunodeficiency virus (HIV) co-infection. The primary outcome was self-reported initiation of breastfeeding or provision of expressed breast milk. Secondary outcomes included duration of breastfeeding. Demographic and obstetric characteristics were compared between those who initiated breastfeeding and those who did not to identify associated factors. Univariable and …

Desirability Of Outcome Ranking For Obstetrical Trials: Illustration And Application To The Arrive Trial, Grecio J Sandoval, William A Grobman, Scott R Evans, Madeline M Rice, Rebecca G Clifton, Suneet P Chauhan, Maged M Costantine, Kelly S Gibson, Monica Longo, Torri D Metz, Emily S Miller, Samuel Parry, Uma M Reddy, Dwight J Rouse, Hyagriv N Simhan, John M Thorp, Alan T N Tita, George R Saade

Faculty, Staff and Student Publications

BACKGROUND: In randomized trials, 1 primary outcome is typically chosen to evaluate the consequences of an intervention, whereas other important outcomes are relegated to secondary outcomes. This issue is amplified for many obstetrical trials in which an intervention may have consequences for both the pregnant person and the child. In contrast, desirability of outcome ranking, a paradigm shift for the design and analysis of clinical trials based on patient-centric evaluation, allows multiple outcomes-including from >1 individual-to be considered concurrently.

OBJECTIVE: This study aimed to describe desirability of outcome ranking methodology tailored to obstetrical trials and to apply the methodology to …

Polygenic Risk Scores, Radiation Treatment Exposures And Subsequent Cancer Risk In Childhood Cancer Survivors, Todd M Gibson, Danielle M Karyadi, Stephen W Hartley, Michael A Arnold, Amy Berrington De Gonzalez, Miriam R Conces, Rebecca M Howell, Vidushi Kapoor, Wendy M Leisenring, Joseph P Neglia, Joshua N Sampson, Lucie M Turcotte, Stephen J Chanock, Gregory T Armstrong, Lindsay M Morton

Faculty, Staff and Student Publications

Survivors of childhood cancer are at increased risk for subsequent cancers attributable to the late effects of radiotherapy and other treatment exposures; thus, further understanding of the impact of genetic predisposition on risk is needed. Combining genotype data for 11,220 5-year survivors from the Childhood Cancer Survivor Study and the St Jude Lifetime Cohort, we found that cancer-specific polygenic risk scores (PRSs) derived from general population, genome-wide association study, cancer loci identified survivors of European ancestry at increased risk of subsequent basal cell carcinoma (odds ratio per s.d. of the PRS: OR = 1.37, 95% confidence interval (CI) = 1.29-1.46), …

The Efficacy-Associated Biomarkers For Immune Checkpoint Inhibitors In Gastrointestinal Cancer: A Literature Review, Jessie Lee, Yifei Shan, Angelique Wong, Elizabeth A Brown, Mitchell Callahan, Robert A Hernandez, Michael J Mienaltowski

Faculty, Staff and Student Publications

White striping (WS) is a common myopathy seen in fast-growing broilers. Studies have demonstrated that chitosan is effective as an antioxidant and has antiobesity and fat-absorption reduction properties. We hypothesized that the dietary supplementation of chitosan would have similar effects when fed to fast-growing broilers and would thus lower WS incidence and improve meat quality. One hundred twenty-six broilers were fed corn-soy diets. The grower and finisher diets contained either 0, 0.2, or 0.4% chitosan. After a 6 wk growth period, birds were euthanized, and then WS and gross pathology scores were assessed. Pectoralis major tissues were collected to evaluate …

Polygenic Risk Scores, Radiation Treatment Exposures And Subsequent Cancer Risk In Childhood Cancer Survivors, Todd M Gibson, Danielle M Karyadi, Stephen W Hartley, Michael A Arnold, Amy Berrington De Gonzalez, Miriam R Conces, Rebecca M Howell, Vidushi Kapoor, Wendy M Leisenring, Joseph P Neglia, Joshua N Sampson, Lucie M Turcotte, Stephen J Chanock, Gregory T Armstrong, Lindsay M Morton

Faculty, Staff and Student Publications

Survivors of childhood cancer are at increased risk for subsequent cancers attributable to the late effects of radiotherapy and other treatment exposures; thus, further understanding of the impact of genetic predisposition on risk is needed. Combining genotype data for 11,220 5-year survivors from the Childhood Cancer Survivor Study and the St Jude Lifetime Cohort, we found that cancer-specific polygenic risk scores (PRSs) derived from general population, genome-wide association study, cancer loci identified survivors of European ancestry at increased risk of subsequent basal cell carcinoma (odds ratio per s.d. of the PRS: OR = 1.37, 95% confidence interval (CI) = 1.29-1.46), …

Surrogate Endpoints In Clinical Trials Of P16-Positive Squamous Cell Carcinoma Of The Oropharynx: An Individual Patient Data Meta-Analysis, Laila A Gharzai, Emily Morris, Krithika Suresh, Phuc Felix Nguyen-Tân, David I Rosenthal, Maura L Gillison, Paul M Harari, Adam S Garden, Shlomo Koyfman, Jimmy J Caudell, Christopher U Jones, Darrion L Mitchell, Greg Krempl, John A Ridge, Michael F Gensheimer, James A Bonner, Edith Filion, Neal E Dunlap, William A Stokes, Quynh-Thu Le, Pedro Torres-Saavedra, Michelle Mierzwa, Matthew J Schipper

Faculty, Staff and Student Publications

Background: The increased incidence of human papillomavirus (HPV)-related cancers has motivated efforts to optimise treatment for these patients with excellent prognosis. Validation of surrogates for overall survival could expedite the investigation of new therapies. We sought to evaluate candidate intermediate clinical endpoints in trials assessing definitive treatment of p16-positive oropharyngeal cancer with chemotherapy or radiotherapy.

Methods: We did a retrospective review of five multicentre, randomised trials (NRG/RTOG 9003, 0129, 0234, 0522, and 1016) that tested radiotherapy with or without chemotherapy in patients (aged ≥18 years) with p16-positive localised head or neck squamous-cell carcinomas. Eight intermediate clinical endpoints were considered as …

Image-Based Multiplex Immune Profiling Of Cancer Tissues: Translational Implications A Report Of The International Immuno-Oncology Biomarker Working Group On Breast Cancer, Chowdhury Arif Jahangir, David B Page, Glenn Broeckx, Claudia A Gonzalez, Caoimbhe Burke, Clodagh Murphy, Jorge S Reis-Filho, Amy Ly, Paul W Harms, Rajarsi R Gupta, Michael Vieth, Akira I Hida, Mohamed Kahila, Zuzana Kos, Paul J Van Diest, Sara Verbandt, Jeppe Thagaard, Reena Khiroya, Khalid Abduljabbar, Gabriela Acosta Haab, Balazs Acs, Sylvia Adams, Jonas S Almeida, Isabel Alvarado-Cabrero, Farid Azmoudeh-Ardalan, Sunil Badve, Nurkhairul Bariyah Baharun, Enrique R Bellolio, Vydehi Bheemaraju, Kim Rm Blenman, Luciana Botinelly Mendonça Fujimoto, Octavio Burgues, Alexandros Chardas, Maggie Chon U Cheang, Francesco Ciompi, Lee Ad Cooper, An Coosemans, Germán Corredor, Flavio Luis Dantas Portela, Frederik Deman, Sandra Demaria, Sarah N Dudgeon, Mahmoud Elghazawy, Claudio Fernandez-Martín, Susan Fineberg, Stephen B Fox, Jennifer M Giltnane, Sacha Gnjatic, Paula I Gonzalez-Ericsson, Anita Grigoriadis, Niels Halama, Matthew G Hanna, Aparna Harbhajanka, Steven N Hart, Johan Hartman, Stephen Hewitt, Hugo M Horlings, Zaheed Husain, Sheeba Irshad, Emiel Am Janssen, Tatsuki R Kataoka, Kosuke Kawaguchi, Andrey I Khramtsov, Umay Kiraz, Pawan Kirtani, Liudmila L Kodach, Konstanty Korski, Guray Akturk, Ely Scott, Anikó Kovács, Anne-Vibeke Laenkholm, Corinna Lang-Schwarz, Denis Larsimont, Jochen K Lennerz, Marvin Lerousseau, Xiaoxian Li, Anant Madabhushi, Sai K Maley, Vidya Manur Narasimhamurthy, Douglas K Marks, Elizabeth S Mcdonald, Ravi Mehrotra, Stefan Michiels, Durga Kharidehal, Fayyaz Ul Amir Afsar Minhas, Shachi Mittal, David A Moore, Shamim Mushtaq, Hussain Nighat, Thomas Papathomas, Frederique Penault-Llorca, Rashindrie D Perera, Christopher J Pinard, Juan Carlos Pinto-Cardenas, Giancarlo Pruneri, Lajos Pusztai, Nasir Mahmood Rajpoot, Bernardo Leon Rapoport, Tilman T Rau, Joana M Ribeiro, David Rimm, Anne Vincent-Salomon, Joel Saltz, Shahin Sayed, Evangelos Hytopoulos, Sarah Mahon, Kalliopi P Siziopikou, Christos Sotiriou, Albrecht Stenzinger, Maher A Sughayer, Daniel Sur, Fraser Symmans, Sunao Tanaka, Timothy Taxter, Sabine Tejpar, Jonas Teuwen, E Aubrey Thompson, Trine Tramm, William T Tran, Jeroen Van Der Laak, Gregory E Verghese, Giuseppe Viale, Noorul Wahab, Thomas Walter, Yannick Waumans, Hannah Y Wen, Wentao Yang, Yinyin Yuan, John Bartlett, Sibylle Loibl, Carsten Denkert, Peter Savas, Sherene Loi, Elisabeth Specht Stovgaard, Roberto Salgado, William M Gallagher, Arman Rahman

Faculty, Staff and Student Publications

Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing the phenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinically relevant biomarkers with high-throughput multiplex immunophenotyping of tumour …

Prenatal Vs Postnatal Diagnosis Of 22q112 Deletion Syndrome: Cardiac And Noncardiac Outcomes Through 1 Year Of Age, Lindsay R Freud, Stephanie Galloway, T Blaine Crowley, Julie Moldenhauer, Ann Swillen, Jeroen Breckpot, Antoni Borrell, Neeta L Vora, Bettina Cuneo, Hilary Hoffman, Lisa Gilbert, Beata Nowakowska, Maciej Geremek, Anna Kutkowska-Kaźmierczak, Joris R Vermeesch, Koen Devriendt, Tiffany Busa, Sabine Sigaudy, Trisha Vigneswaran, John M Simpson, Jeffrey Dungan, Nina Gotteiner, Karl-Philipp Gloning, Maria Cristina Digilio, Marta Unolt, Carolina Putotto, Bruno Marino, Gabriela Repetto, Magdalena Fadic, Sixto Garcia-Minaur, Ana Achón Buil, Mary Ann Thomas, Deborah Fruitman, Taylor Beecroft, Pui Wah Hui, Solveig Oskarsdottir, Rachael Bradshaw, Amanda Criebaum, Mary E Norton, Tiffany Lee, Miwa Geiger, Leslie Dunnington, Jacqueline Isaac, Louise Wilkins-Haug, Lindsey Hunter, Claudia Izzi, Marika Toscano, Tullio Ghi, Julie Mcglynn, Francesca Romana Grati, Beverly S Emanuel, Kimberly Gaiser, J William Gaynor, Elizabeth Goldmuntz, Daniel E Mcginn, Erica Schindewolf, Oanh Tran, Elaine H Zackai, Qi Yan, Anne S Bassett, Ronald Wapner, Donna M Mcdonald-Mcginn

Faculty, Staff and Student Publications

Background: The 22q11.2 deletion syndrome is the most common microdeletion syndrome and is frequently associated with congenital heart disease. Prenatal diagnosis of 22q11.2 deletion syndrome is increasingly offered. It is unknown whether there is a clinical benefit to prenatal detection as compared with postnatal diagnosis.

Objective: This study aimed to determine differences in perinatal and infant outcomes between patients with prenatal and postnatal diagnosis of 22q11.2 deletion syndrome.

Study design: This was a retrospective cohort study across multiple international centers (30 sites, 4 continents) from 2006 to 2019. Participants were fetuses, neonates, or infants with a genetic diagnosis of 22q11.2 …

Migraines, Vasomotor Symptoms, And Cardiovascular Disease In The Coronary Artery Risk Development In Young Adults Study, Catherine Kim, Pamela J Schreiner, Zhe Yin, Rachael Whitney, Stephen Sidney, Imo Ebong, Deborah A Levine

Faculty, Staff and Student Publications

Objective: To examine whether vasomotor symptoms (VMS) and migraine headaches, hypothesized to be vasoactive conditions, are associated with greater risk for cardiovascular disease (CVD) events including strokes.

Methods: We performed a secondary data analysis of a subset of women (n = 1,954) in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based cohort, which began data collection at 18 to 30 y of age. We examined whether migraine headaches and VMS trajectories (characterized as minimal, increasing, and persistent) at CARDIA year 15 examination were associated with higher risk of CVD events and stroke (both ischemic and hemorrhagic) …

Diras3 Induces Autophagy And Enhances Sensitivity To Anti-Autophagic Therapy In Kras-Driven Pancreatic And Ovarian Carcinomas, Gamze Bildik, Joshua P Gray, Weiqun Mao, Hailing Yang, Rumeysa Ozyurt, Vivian R Orellana, Olivier De Wever, Mark S Carey, Robert C Bast, Zhen Lu

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) and low-grade ovarian cancer (LGSOC) are characterized by the prevalence of KRAS oncogene mutations. DIRAS3 is the first endogenous non-RAS protein that heterodimerizes with RAS, disrupts RAS clustering, blocks RAS signaling, and inhibits cancer cell growth. Here, we found that DIRAS3-mediated KRAS inhibition induces ROS-mediated apoptosis in PDAC and LGSOC cells with KRAS mutations, but not in cells with wild-type KRAS, by downregulating NFE2L2/Nrf2 transcription, reducing antioxidants, and inducing oxidative stress. DIRAS3 also induces cytoprotective macroautophagy/autophagy that may protect mutant KRAS cancer cells from oxidative stress, by inhibiting mutant KRAS, activating the STK11/LKB1-PRKAA/AMPK pathway, increasing lysosomal …

Real-World Efficacy And Safety Of Amivantamab For Egfr-Mutant Nsclc, Kaiwen Wang, Robyn Du, Nathaniel J Myall, Whitney E Lewis, Natalie Uy, Lingzhi Hong, Ferdinandos Skoulidis, Lauren A Byers, Anne Tsao, Tina Cascone, Jenny Pozadzides, Janet Tu, Marcelo V Negrao, Don L Gibbons, Keunchil Park, Waree Rinsurongkawong, J Jack Lee, David Gandara, Deepti Behl, Catherine A Shu, Jonathan W Riess, Christina Baik, Heather A Wakelee, Ara A Vaporciyan, John V Heymach, Jianjun Zhang, Xiuning Le

Faculty, Staff and Student Publications

Introduction: Amivantamab-vmjw (amivantamab) is a bispecific EGFR/MET antibody approved for patients with advanced NSCLC with EGFR exon 20 insertion mutations, after prior therapy. Nevertheless, the benefits and safety of amivantamab in other EGFR-mutant lung cancer, with or without osimertinib, and with concurrent radiation therapy, are less known.

Methods: We queried the MD Anderson Lung Cancer GEMINI, Fred Hutchinson Cancer Research Center, University of California Davis Comprehensive Cancer Center, and Stanford Cancer Center's database for patients with EGFR-mutant NSCLC treated with amivantamab, not on a clinical trial. The data analyzed included initial response, duration of treatment, and concomitant radiation safety in …

Watching The Fall Of Roe V Wade: Media Exposure Relates To Us Women's Alcohol Use Intentions, Stacy M Post, Mary C Jobe, Arianne N Malekzadeh, Katarina E Aubuchon, Rebecca K Hoffman, Michelle L Stock, Lisa Bowleg

Faculty, Staff and Student Publications

OBJECTIVE: The Supreme Court of the United States’ decision in Dobbs v. Jackson Women’s Health Organization in June 2022 overturned Roe v. Wade and ended federal protection of abortion rights. Given the drastic policy changes as a result of the ruling and high exposure to media related to abortion, women opposed to the decision may have experienced distress, which could trigger maladaptive coping strategies, such as alcohol use. The present research examined how consuming abortion-related media in the weeks following the Dobbs decision impacted alcohol use intentions among women of reproductive age residing in the 13 “trigger law” states that …

Outcomes In 14 Live Births Resulting From Pegvaliase-Treated Pregnancies In Pku-Affected Females, Caide Bier, Kaelin Dickey, Brittan Bibb, Angela Crutcher, Rebecca Sponberg, Richard Chang, Monica Boyer, Laura Davis-Keppen, Cindy Matthes, Michelle Tharp, Danielle Vice, Erin Cooney, Megan Morand, Joseph Ray, Melissa Lah, Markey Mcnutt, Hans C Andersson

Faculty, Staff and Student Publications

Background: Adults with PKU have difficulty maintaining plasma phenylalanine (Phe) in the range that is safe for neurologic function. Elevated plasma Phe is a risk factor for congenital anomalies and developmental delay in offspring resulting from pregnancies with poor Phe control in women with PKU. Enzyme supplementation with pegvaliase allows adults with PKU to eat an unrestricted diet and have plasma Phe levels in a safe range for pregnancy but pegvaliase has not been approved for use in pregnant females with PKU. We report the results of chart review of 14 living offspring of females affected with PKU who were …

A Study Of Dietary Patterns Derived By Cluster Analysis And Their Association With Metabolic Dysfunction-Associated Steatotic Liver Disease Severity Among Hispanic Patients, Xiaotao Zhang, Carrie R Daniel, Valeria Soltero, Ximena Vargas, Shilpa Jain, Fasiha Kanwal, Aaron P Thrift, Maya Balakrishnan

Faculty, Staff and Student Publications

Introduction: Diet is a modifiable metabolic dysfunction-associated steatotic liver disease (MASLD) risk factor, but few studies have been conducted among Hispanic patients, despite the fact that MASLD prevalence and severity are highest among this ethnic subgroup. We aimed to identify prevalent dietary patterns among Hispanic patients using cluster analysis and to investigate associations with MASLD severity.

Methods: This cross-sectional analysis included 421 Harris County MASLD Cohort participants who self-reported Hispanic ethnicity and completed baseline food frequency questionnaires. All included patients had MASLD, diagnosed per standard clinical criteria. K-means analysis was used to identify clusters of patients sharing similar dietary habits. …

Case Sampling For Evaluating Hospital Postoperative Morbidity In Us Surgical Quality Improvement Programs, Vivi W Chen, Tracey Rosen, Yongquan Dong, Peter A Richardson, Jennifer R Kramer, Laura A Petersen, Nader N Massarweh

Center for Medical Ethics and Health Policy Staff Publications

Importance: US surgical quality improvement (QI) programs use data from a systematic sample of surgical cases, rather than universal review of all cases, to assess and compare risk-adjusted hospital postoperative complication rates. Given decreasing postoperative complication rates over time and the types of cases eligible for abstraction, it is unclear whether case sampling is robust for identifying hospitals with higher than expected complications.

Objective: To compare the assessment of hospital 30-day complication rates derived from sampling strategy used by some US surgical QI programs relative to universal review of all cases.

Design, setting, and participants: This US hospital-level analysis took …