Medical Specialties Commons^™

Radiomics In Abdominopelvic Solid-Organ Oncologic Imaging: Current Status, Xiaoyang Liu, Mohamed G Elbanan, Antonio Luna, Masoom A Haider, Andrew D Smith, Carl F Sabottke, Bradley M Spieler, Baris Turkbey, David Fuentes, Ahmed Moawad, Serageldin Kamel, Natally Horvat, Khaled M Elsayes

Faculty, Staff and Student Publications

Radiomics is the process of extraction of high-throughput quantitative imaging features from medical images. These features represent noninvasive quantitative biomarkers that go beyond the traditional imaging features visible to the human eye. This article first reviews the steps of the radiomics pipeline, including image acquisition, ROI selection and image segmentation, image preprocessing, feature extraction, feature selection, and model development and application. Current evidence for the application of radiomics in abdominopelvic solid-organ cancers is then reviewed. Applications including diagnosis, subtype determination, treatment response assessment, and outcome prediction are explored within the context of hepatobiliary and pancreatic cancer, renal cell carcinoma, prostate …

International Pooled Patient-Level Meta-Analysis Of Ketamine Infusion For Depression: In Search Of Clinical Moderators, Rebecca B Price, Nicholas Kissel, Andrew Baumeister, Rebecca Rohac, Mary L Woody, Elizabeth D Ballard, Carlos A Zarate, William Deakin, Chadi G Abdallah, Adriana Feder, Dennis S Charney, Michael F Grunebaum, J John Mann, Sanjay J Mathew, Bronagh Gallagher, Declan M Mcloughlin, James W Murrough, Suresh Muthukumaraswamy, Rebecca Mcmillan, Rachael Sumner, George Papakostas, Maurizio Fava, Rebecca Hock, Jennifer L Phillips, Pierre Blier, Paulo Shiroma, Peter Šóš, Tung-Ping Su, Mu-Hong Chen, Mikael Tiger, Johan Lundberg, Samuel T Wilkinson, Meredith L Wallace

Children’s Nutrition Research Center Staff Publications

Depression is disabling and highly prevalent. Intravenous (IV) ketamine displays rapid-onset antidepressant properties, but little is known regarding which patients are most likely to benefit, limiting personalized prescriptions. We identified randomized controlled trials of IV ketamine that recruited individuals with a relevant psychiatric diagnosis (e.g., unipolar or bipolar depression; post-traumatic stress disorder), included one or more control arms, did not provide any other study-administered treatment in conjunction with ketamine (although clinically prescribed concurrent treatments were allowable), and assessed outcome using either the Montgomery-Åsberg Depression Rating Scale or the Hamilton Rating Scale for Depression (HRSD-17). Individual patient-level data for at least …

Clinical And Molecular Profiling Of Aml Patients With Chromosome 7 Or 7q Deletions In The Context Of Tp53 Alterations And Venetoclax Treatment, Hussein A Abbas, Edward Ayoub, Hanxiao Sun, Rashmi Kanagal-Shamanna, Nicholas J Short, Ghayas Issa, Musa Yilmaz, Sherry Pierce, Daniel Rivera, Brent Cham, Shane Wing, Ziyi Li, Danielle Hammond, Elias Jabbour, Gautam Borthakur, Guillermo Garcia-Manero, Michael Andreeff, Naval Daver, Tapan Kadia, Marina Konopleva, Courtney Dinardo, Farhad Ravandi

Faculty, Staff and Student Publications

Deletions in chromosome 7 (del(7)) or its long arm (del(7q)) constitute the most common adverse cytogenetic events in acute myeloid leukemia (AML). We retrospectively analyzed 243 treatment-naive patients with AML and del(7) (168/243; 69%) or del(7q) (75/243; 31%) who did not receive any myeloid-directed therapy prior to AML diagnosis. This is the largest comprehensive clinical and molecular analysis of AML patients with del(7) and del(7q). Our results show that relapse-free survival was significantly longer for AML patients with del(7q) compared to del(7), but the overall survival and remission duration were similar. TP53 mutations and del5/5q were the most frequent co-occurring …

Inclusion Of Premenopausal Women In Breast Cancer Clinical Trials, Kelsey L Corrigan, Ramez Kouzy, Joseph Abi Jaoude, Roshal R Patel, Rachel M Layman, Sharon H Giordano, Wendy A Woodward, Benjamin D Smith, Simona F Shaitelman, Ethan B Ludmir

Faculty, Staff and Student Publications

BACKGROUND: Patients with premenopausal breast cancer (PMBC) have been historically excluded from some clinical trials because of the limitations of using endocrine therapy (ET) in this population. We analyzed breast cancer randomized clinical trials (RCTs) to determine the rates of and factors associated with inclusion of PMBC patients to provide a benchmark for PMBC inclusion in RCTs moving forward.

METHODS: Using ClinicalTrials.Gov, we identified breast cancer phase III RCTs and extracted inclusion criteria and patient enrollment information. Multiple binary logistic regression modeling was used to assess trial-related factors that were associated with PMBC patient inclusion.

RESULTS: Of 170 breast …

Obstetric And Neonatal Outcomes 1 Or More Years After A Diagnosis Of Breast Cancer, Kirsten Jorgensen, Roni Nitecki, Hazel B Nichols, Shuangshuang Fu, Chi-Fang Wu, Alexander Melamed, Paula Brady, Mariana Chavez Mac Gregor, Mark A Clapp, Sharon Giordano, J Alejandro Rauh-Hain

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate obstetric and neonatal outcomes of the first live birth conceived 1 or more years after breast cancer diagnosis.

METHODS: We performed a population-based study to compare live births between women with a history of breast cancer (case group) and matched women with no cancer history (control group). Individuals in the case and control groups were identified using linked data from the California Cancer Registry and California Office of Statewide Health Planning and Development data sets. Individuals in the case group were diagnosed with stage I-III breast cancer at age 18-45 years between January 1, 2000, and December …

An Optimized Cell-Based Assay To Assess Influenza Virus Replication By Measuring Neuraminidase Activity And Its Applications For Virological Surveillance, Mira C Patel, Daniel Flanigan, Chenchen Feng, Anton Chesnokov, Ha T Nguyen, Anwar Abd Elal, John Steel, Rebecca J Kondor, David E Wentworth, Larisa V Gubareva, Vasiliy P Mishin

Faculty, Staff and Student Publications

Year-round virological characterization of circulating epidemic influenza viruses is conducted worldwide to detect the emergence of viruses that may escape pre-existing immunity or acquire resistance to antivirals. High throughput phenotypic assays are needed to complement the sequence-based analysis of circulating viruses and improve pandemic preparedness. The recent entry of a polymerase inhibitor, baloxavir, into the global market further highlighted this need. Here, we optimized a cell-based assay that considerably streamlines antiviral and antigenic testing by replacing lengthy immunostaining and imaging procedures used in current assay with measuring the enzymatic activity of nascent neuraminidase (NA) molecules expressed on the surface of …

Association Of Patient Belief About Success Of Antibiotics For Appendicitis And Outcomes: A Secondary Analysis Of The Coda Randomized Clinical Trial, Writing Group For The Coda Collaborative, Irene Y Zhang, Emily C Voldal, Giana H Davidson, Joshua M Liao, Callie M Thompson, Wesley H Self, Lillian S Kao, Jill Cherry-Bukowiec, Krishnan Raghavendran, Amy H Kaji, Daniel A Deugarte, Eva Gonzalez, Katherine A Mandell, Kristen Ohe, Nicole Siparsky, Thea P Price, David C Evans, Jesse Victory, William Chiang, Alan Jones, Matthew E Kutcher, Hailie Ciomperlik, Mike K Liang, Heather L Evans, Brett A Faine, Miriam Neufeld, Sabrina E Sanchez, Anusha Krishnadasan, Bryan A Comstock, Patrick J Heagerty, Sarah O Lawrence, Sarah E Monsell, Erin E C Fannon, Larry G Kessler, David A Talan, David R Flum

Faculty, Staff and Student Publications

IMPORTANCE: A patient's belief in the likely success of a treatment may influence outcomes, but this has been understudied in surgical trials.

OBJECTIVE: To examine the association between patients' baseline beliefs about the likelihood of treatment success with outcomes of antibiotics for appendicitis in the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial.

DESIGN, SETTING, AND PARTICIPANTS: This was a secondary analysis of the CODA randomized clinical trial. Participants from 25 US medical centers were enrolled between May 3, 2016, and February 5, 2020. Included in the analysis were participants with appendicitis who were randomly assigned to receive …

Continued Treatment With Nintedanib In Patients With Systemic Sclerosis-Associated Interstitial Lung Disease: Data From Senscis-On, Yannick Allanore, Madelon C Vonk, Oliver Distler, Arata Azuma, Maureen D Mayes, Martina Gahlemann, Alexandra James, Veronika Kohlbrenner, Margarida Alves, Dinesh Khanna, Kristin B Highland, Senscis-On Trial Investigators

Faculty, Staff and Student Publications

Objectives: In the SENSCIS trial in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD), nintedanib reduced the rate of decline in forced vital capacity (FVC) versus placebo, with adverse events that were manageable for most patients. An open-label extension trial, SENSCIS-ON, is assessing safety and FVC decline during longer term nintedanib treatment.

Methods: Patients who completed the SENSCIS trial or a drug-drug interaction (DDI) study of nintedanib and oral contraceptive on treatment were eligible to enter SENSCIS-ON. Adverse events and changes in FVC over 52 weeks of SENSCIS-ON were assessed in patients who received nintedanib in SENSCIS and continued nintedanib …

Non-Traumatic Open Globe Injuries: Presenting Characteristics And Visual Outcomes, Andrew W Gross, James Z Fan, Margaret L Pfeiffer, Alice Z Chuang, Karina Richani, Eric L Crowell

Faculty, Staff and Student Publications

Purpose: To describe clinical characteristics and visual outcomes of non-traumatic open globe injuries.

Setting: A level 1 trauma centre in a large urban medical centre.

Design: Retrospective study.

Methods: Charts of non-traumatic open globe patients admitted to MHH-TMC from 1/2010 to 3/2015 were reviewed for demographics, cause, clinical characteristics, visual acuity (VA) and enucleation.

Results: Thirty eyes were included: 15 (50%) were males with a mean age of 47 (±28) years. All presented with zone 1 injury. Twenty-five (83%) had a perforated corneal ulcer. Presenting VA was count fingers (n = 3, 10%) to NLP (n = 6, 20%). Twenty-four …

Evaluation Of Murine Host Sex As A Biological Variable In Transplanted Human Intestinal Organoid Development, Eoin P Mcneill, Vikas S Gupta, David J Sequeira, Noah F Shroyer, Allison L Speer

Faculty, Staff and Student Publications

Background: Human intestinal organoids (HIOs), when transplanted into immunocompromised mice (tHIOs), demonstrate significant growth and maturation. While both male and female mice are reported to be viable hosts for these experiments, a direct comparison of sex-related differences in tHIO structure and development has not been performed.

Aims: We sought to identify host sex-related differences in tHIO engraftment, morphology, and epithelial and mesenchymal development.

Methods: HIOs were generated in vitro and transplanted beneath the kidney capsule of NSG male and female mice. tHIOs were harvested at 8-9 weeks. Anthropometric measurements were captured. tHIOs were divided in half and histology or RT-qPCR …

Effects Of Gabapentin And Pregabalin On Calcium Homeostasis: Implications For Physical Rehabilitation Of Musculoskeletal Tissues, Perla C Reyes Fernandez, Christian S Wright, Stuart J Warden, Julia Hum, Mary C Farach-Carson, William R Thompson

Faculty, Staff and Student Publications

Purpose of review: In this review, we discuss the mechanism of action of gabapentinoids and the potential consequences of long-term treatment with these drugs on the musculoskeletal system.

Recent findings: Gabapentinoids, such as gabapentin (GBP) and pregabalin (PGB) were designed as antiepileptic reagents and are now commonly used as first-line treatment for neuropathic pain and increasingly prescribed off-label for other pain disorders such as migraines and back pain. GBP and PGB exert their analgesic actions by selectively binding the α2δ1 auxiliary subunit of voltage-sensitive calcium channels, thereby inhibiting channel function. Numerous tissues express the α2δ1 subunit where GBP and PGB …

Reproducing Statistics Performed In Published Randomized Controlled Trials, Naila H Dhanani, Oscar A Olavarria, Cynthia S Bell, Julie L Holihan, Mike K Liang

Faculty, Staff and Student Publications

INTRODUCTION: Randomized controlled trials (RCT) represent evidence at the lowest potential risk for bias. Clinicians in all specialties depend upon RCTs to guide patient care. Issues such as statistical discordance, or reporting statistical results that cannot be reproduced, should be uncommon. Our aim was to confirm the statistical reproducibility of published RCTs.

METHODS: PubMed was searched using "randomized controlled trial." Studies were selected using a random number generator. Studies were included if the primary outcome could be reproduced using the data and statistical test reported in the manuscript. The reproduced p-value from our analysis and the published p-value were compared. …

Etiology And Pathophysiology Of Hypoparathyroidism: A Narrative Review, Janice L Pasieka, Kelly Wentworth, Caitlin T Yeo, Serge Cremers, David Dempster, Seiji Fukumoto, Ravinder Goswami, Pascal Houillier, Michael A Levine, Jesse D Pasternak, Nancy D Perrier, Antonio Sitges-Serra, Dolores M Shoback

Faculty, Staff and Student Publications

The approach utilized a systematic review of the medical literature executed with specifically designed criteria that focused on the etiologies and pathogenesis of hypoparathyroidism. Enhanced attention by endocrine surgeons to new knowledge about parathyroid gland viability are reviewed along with the role of intraoperative parathyroid hormone (ioPTH) monitoring during and after neck surgery. Nonsurgical etiologies account for a significant proportion of cases of hypoparathyroidism (~25%), and among them, genetic etiologies are key. Given the pervasive nature of PTH deficiency across multiple organ systems, a detailed review of the skeletal, renal, neuromuscular, and ocular complications is provided. The burden of illness …

Clinically Significant Metachronous Colorectal Pathology Detected Among Young-Onset Colorectal Cancer Survivors: Implications For Post-Resection Surveillance Guidelines, Oliver Peacock, Eduardo Vilar, Montserrat Guraieb-Trueba, Selvi Thirumurthi, George J Chang, Y Nancy You

Faculty, Staff and Student Publications

No abstract provided.

Delayed-Interval Delivery In Multiple Gestation Pregnancies: Neonatal Mortality, Morbidity, And Development, Nicolas J Bouey, Shampa Saha, Deanne E Wilson-Costello, Matthew A Rysavy, Michele Walsh, Myra H Wyckoff, Anna Maria Hibbs

Faculty, Staff and Student Publications

OBJECTIVE: Delayed-interval delivery (DID) is the delivery of the first fetus in a multiple gestation pregnancy without prompt delivery of the remaining fetus(es). We aimed to assess infant outcomes of DID.

STUDY DESIGN: We performed a retrospective cohort study of infants born 22-28 weeks' gestation or weighing 401-1500 g. DID was defined as a passage of >24 h between the birth of firstborn and retained infants. Rates of mortality, morbidity, and developmental outcomes were compared within DID multiples, to other multiples not born by DID, and all infants in the Generic Database and follow-up datasets (excluding DID-born).

RESULTS: DID-born multiples …

Utility Of Measurable Residual Disease For Predicting Treatment Outcomes With Bcr- And Bcl2-Targeted Therapies In Patients With Cll, William G Wierda, Thomas J Kipps, Othman Al-Sawaf, Brenda Chyla, Juliana M L Biondo, Yong Mun, Yanwen Jiang, John F Seymour

Faculty, Staff and Student Publications

Inhibitors targeting B-cell receptor (BCR) signaling pathway proteins and B-cell lymphoma-2 (BCL2) in chronic lymphocytic leukemia (CLL) are recommended in the first-line and relapsed/refractory disease settings. Measurable residual disease (MRD) is an important prognostic tool in patients treated with the BCL2-targeted agent, venetoclax. We explored the relationship between MRD status and progression-free (PFS)/overall survival (OS) in patients with CLL, following treatment with novel BCR- and BCL2-targeted agents. Compared with chemoimmunotherapy, higher rates of undetectable (u)MRD were achieved with BCL2-targeted therapies; achieving uMRD status was associated with longer PFS and OS than MRD-positivity. Continuous treatment with BCR-targeted agents did not achieve …

Association Of Initial Sars-Cov-2 Test Positivity With Patient-Reported Well-Being 3 Months After A Symptomatic Illness, Lauren E Wisk, Michael A Gottlieb, Erica S Spatz, Huihui Yu, Ralph C Wang, Benjamin H Slovis, Sharon Saydah, Ian D Plumb, Kelli N O'Laughlin, Juan Carlos C Montoy, Samuel A Mcdonald, Zhenqiu Lin, Jin-Mann S Lin, Katherine Koo, Ahamed H Idris, Ryan M Huebinger, Mandy J Hill, Nicole L Gentile, Anna Marie Chang, Jill Anderson, Bala Hota, Arjun K Venkatesh, Robert A Weinstein, Joann G Elmore, Graham Nichol, Inspire Group

Faculty, Staff and Student Publications

IMPORTANCE: Long-term sequelae after symptomatic SARS-CoV-2 infection may impact well-being, yet existing data primarily focus on discrete symptoms and/or health care use.

OBJECTIVE: To compare patient-reported outcomes of physical, mental, and social well-being among adults with symptomatic illness who received a positive vs negative test result for SARS-CoV-2 infection.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was a planned interim analysis of an ongoing multicenter prospective longitudinal registry study (the Innovative Support for Patients With SARS-CoV-2 Infections Registry [INSPIRE]). Participants were enrolled from December 11, 2020, to September 10, 2021, and comprised adults (aged ≥18 years) with acute symptoms suggestive …

Freedom As Prevention: Mechanisms Of Autonomy Support For Promoting Hiv Pre-Exposure Prophylaxis Use And Condom Use Among Black Msm In 3 Us Cities—Hptn 073, Laron E Nelson, Donte T Boyd, Geetha Beauchamp, Lynda Emel, Leo Wilton, Darren Whitfield, S Raquel Ramos, Wale Ajiboye, Mandy J Hill, Donaldson F Conserve, Portia Thomas, Lisa Hightow-Weidman, Steve Shoptaw, Manya Magnus, Kenneth H Mayer, Estelle Piwowar-Manning, Sheldon D Fields, Darrell P Wheeler, Hptn 073 Study Team

Faculty, Staff and Student Publications

Healthcare providers who use controlling or coercive strategies may compel short-term enactment of HIV and sexually transmitted infection prevention behaviors but may inadvertently undermine their client's motivation to maintain those behaviors in the absence of external pressure. Autonomous motivation refers to the self-emanating and self-determined drive for engaging in health behaviors. It is associated with long-term maintenance of health behaviors. We used structural equation modeling to investigate whether autonomy support was associated with increased odds of therapeutic serum levels of pre-exposure prophylaxis, through a pathway that satisfies basic psychological needs for autonomous self-regulation and competence regarding pre-exposure prophylaxis use. We …

Chemoradiation Therapy Alters The Pd-L1 Score In Locoregional Recurrent Squamous Cell Carcinomas Of The Head And Neck, Brian J Park, Austin K Mattox, Daniel Clayburgh, Mihir Patel, R Bryan Bell, Bevan Yueh, Rom Leidner, Hong Xiao, Marcus Couey, Shiting Li, Tingting Qin, Maureen A Sartor, Belinda Cairns, Tracy Macdonough, Kyle Halliwill, Daniel Deschler, Derrick T Lin, William C Faquin, Peter M Sadow, Sara I Pai

Faculty, Staff and Student Publications

PD-L1 testing guides therapeutic decision-making for head and neck squamous cell carcinoma (HNSCC). We sought to understand whether chemoradiation therapy (CRT) influences the PD-L1 combined positive score (CPS) and other biomarkers of response to immunotherapy. PD-L1 expression was assessed using immunohistochemistry, and bulk RNA sequencing was performed on 146 HNSCC patients (65 primary sites, 50 paired local recurrences, and 31 paired regional recurrences). PD-L1 was scored using the CPS of ≥1, ≥20, and ≥50. Overall, 98 %, 54 %, and 17 % of HNSCCs had a CPS ≥1, ≥20, and ≥50, respectively. When using a cut-off of ≥1, CRT did …

Liver Injury After Sars‐Cov‐2 Vaccination: Features Of Immune-Mediated Hepatitis, Role Of Corticosteroid Therapy And Outcome, Cumali Efe, Anand V Kulkarni, Benedetta Terziroli Beretta-Piccoli, Bianca Magro, Albert Stättermayer, Mustafa Cengiz, Daniel Clayton-Chubb, Craig Lammert, Christine Bernsmeier, Özlem Gül, Fatima Higuera-De La Tijera, Margarita Anders, Ellina Lytvyak, Mete Akın, Tugrul Purnak, Rodrigo Liberal, Mirta Peralta, Berat Ebik, Serkan Duman, Nurhan Demir, Yasemin Balaban, Álvaro Urzua, Fernando Contreras, Maria Grazia Venturelli, Yılmaz Bilgiç, Adriana Medina, Marcos Girala, Fulya Günşar, Maria-Carlota Londoño, Theodoros Androutsakos, Ayelen Kisch, Alper Yurci, Fatih Güzelbulut, Yasir Furkan Çağın, Enver Avcı, Murat Akyıldız, Emine Kübra Dindar-Demiray, Murat Harputluoğlu, Rahul Kumar, Sanjaya K Satapathy, Manuel Mendizabal, Marcelo Silva, Stefano Fagiuoli, Stuart K Roberts, Neşe Karadağ Soylu, Ramazan Idilman, Eric M Yoshida, Aldo J Montano-Loza, George N Dalekos, Ezequiel Ridruejo, Thomas D Schiano, Staffan Wahlin

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: A few case reports of autoimmune hepatitis-like liver injury have been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. We evaluated clinical features, treatment response and outcomes of liver injury following SARS-CoV-2 vaccination in a large case series.

APPROACH AND RESULTS: We collected data from cases in 18 countries. The type of liver injury was assessed with the R-value. The study population was categorized according to features of immune-mediated hepatitis (positive autoantibodies and elevated immunoglobulin G levels) and corticosteroid therapy for the liver injury. We identified 87 patients (63%, female), median age 48 (range: 18-79) …

Implications Of Ras Mutational Status In Subsets Of Patients With Newly Diagnosed Acute Myeloid Leukemia Across Therapy Subtypes, Daniel Rivera, Kunhwa Kim, Rashmi Kanagal-Shamanna, Gautam Borthakur, Guillermo Montalban-Bravo, Naval Daver, Courtney Dinardo, Nicholas J Short, Musa Yilmaz, Naveen Pemmaraju, Koichi Takahashi, Elias J Jabbour, Sherry Pierce, Marina Konopleva, Kapil Bhalla, Guillermo Garcia-Manero, Farhad Ravandi, Hagop Kantarjian, Tapan M Kadia

Faculty, Staff and Student Publications

Activating mutations in RAS have been reported in about 10-15% of patients with AML; previous studies have not identified a prognostic significance. However, RAS mutations have emerged as a potential resistance mechanism to treatment with inhibitors of FLT3, IDH, and BCL2. We aimed to determine the characteristics and outcomes of patients with RAS-mutated (RAS-mut) AML across therapy subsets of 1410 patients newly diagnosed (ND AML). RAS-mut was observed in 273 (20%) patients. Overall, patients with RAS-mut AML had an estimated 3-year survival rate of 38% vs. 28% in those with RAS wild type (RAS-wt), p = .01. Among patients with …

Pet/Mr Imaging Of A Lung Metastasis Model Of Clear Cell Renal Cell Carcinoma With (2s,4r)-4-[18f]Fluoroglutamine, Alyssa C Pollard, Vincenzo Paolillo, Bhasker Radaram, Sarah Qureshy, Li Li, Tapati Maity, Lei Wang, Md Nasir Uddin, Christopher G Wood, Jose A Karam, Mark D Pagel, David Piwnica-Worms, Steven W Millward, Natalie Wall Fowlkes, William Norton, Brian J Engel, Federica Pisaneschi, Niki M Zacharias

Faculty, Staff and Student Publications

Purpose: Metabolic reprogramming plays an important role in the tumorigenesis of clear cell renal cell carcinoma (ccRCC). Currently, positron emission tomography (PET) reporters are not used clinically to visualize altered glutamine metabolism in ccRCC, which greatly hinders detection, staging, and real-time therapeutic assessment. We sought to determine if (2S,4R)-4-[18F]fluoroglutamine ([18F]FGln) could be used to interrogate altered glutamine metabolism in ccRCC lesions in the lung.

Procedures: We generated a novel ccRCC lung lesion model using the ccRCC cell line UMRC3 stably transfected with GFP and luciferase constructs. This cell line was used for characterization of [18F]FGln uptake and retention by transport …

Genetic Landscape Of Indolent And Aggressive Kaposi Sarcomas, G G Malouf, X Lu, R Mouawad, J-P Spano, P Grange, F Yan, S Aractingi, X Su, N Dupin

Faculty, Staff and Student Publications

Background: Kaposi sarcoma (KS) is a rare skin tumour caused by herpesvirus 8 infection and characterized by either indolence or an aggressive course necessitating systemic therapies. The genetic basis of this difference remains unknown.

Objectives: To explore the tumour mutational burden in indolent and aggressive KS.

Methods: We performed whole-exome sequencing on a cohort of 21 KS patients. We compared genetic landscape including tumor mutational burden between the two forms of indolent and agressive KS.

Results: Aggressive KS tumours had a significantly higher TMB and a larger cumulative number of deleterious mutations than indolent KS tumours. In addition, all aggressive …

Using Single Molecule Molecular Inversion Probes As A Cost-Effective, High-Throughput Sequencing Approach To Target All Genes And Loci Associated With Macular Diseases, Rebekkah J Hitti-Malin, Claire-Marie Dhaenens, Daan M Panneman, Zelia Corradi, Mubeen Khan, Anneke I Den Hollander, G Jane Farrar, Christian Gilissen, Alexander Hoischen, Maartje Van De Vorst, Femke Bults, Erica G M Boonen, Patrick Saunders, Susanne Roosing, Frans P M Cremers

Faculty, Staff and Student Publications

Macular degenerations (MDs) are a subgroup of retinal disorders characterized by central vision loss. Knowledge is still lacking on the extent of genetic and nongenetic factors influencing inherited MD (iMD) and age-related MD (AMD) expression. Single molecule Molecular Inversion Probes (smMIPs) have proven effective in sequencing the ABCA4 gene in patients with Stargardt disease to identify associated coding and noncoding variation, however many MD patients still remain genetically unexplained. We hypothesized that the missing heritability of MDs may be revealed by smMIPs-based sequencing of all MD-associated genes and risk factors. Using 17,394 smMIPs, we sequenced the coding regions of 105 …

A Cluster-Randomized Controlled Trial Of Automated Internet Weight-Loss Programs In Primary Care: Role Of Automated Provider Feedback, Deborah F Tate, Jennifer L Kraschnewski, Caitlin Martinez, Molly Diamond, Susan Veldheer, Kevin O Hwang, Erik B Lehman, Chengwu Yang, Christopher N Sciamanna

Faculty, Staff and Student Publications

OBJECTIVE: Despite the high prevalence of obesity and associated health risks in the United States adult population, few primary care providers (PCPs) have time and training to provide weight-management counseling to their patients. This study aims to compare the effect of referral to a comprehensive automated digital weight-loss program, with or without provider email feedback, with usual care on weight loss in patients with overweight or obesity.

METHODS: A total of 550 adults (mean [SD], 51.4 [11.2] years, BMI = 35.1 [5.5] kg/m

RESULTS: Weight changes (mean [SE]) at 12 months were -0.92 (0.46), -3.68 (0.46), and -3.58 (0.48) kg …

Patient Identification Of Diagnostic Safety Blindspots And Participation In “Good Catches” Through Shared Visit Notes, Sigall K Bell, Fabienne Bourgeois, Joe Dong, Alex Gillespie, Long H Ngo, Tom W Reader, Eric J Thomas, Catherine M Desroches

Faculty, Staff and Student Publications

Policy Points Patients and families can identify clinically relevant errors, including "blindspots"-safety hazards that are difficult for clinicians or organizations to see. Health information transparency, including patient access to electronic visit notes, now federally mandated in the US and the subject of policy debate worldwide, creates a new opportunity to engage patients in diagnostic safety. However, not all patients access notes. Patient identification of blindspots in their notes underscores the need to systematically and equitably engage willing patients in safety, promote patient "good catches," and establish routine systems for patient feedback to help avoid preventable diagnostic errors and delays.

CONTEXT: …

Lymphocyte Sparing Normal Tissue Effects In The Clinic (Lymphotec): A Systematic Review Of Dose Constraint Considerations To Mitigate Radiation-Related Lymphopenia In The Era Of Immunotherapy, Bhanuprasad Venkatesulu, Prashanth Giridhar, Lincoln Pujari, Brian Chou, Jae Han Lee, Alec M Block, Rituraj Upadhyay, James S Welsh, Matthew M Harkenrider, Sunil Krishnan, Vivek Verma, Cheng En Hsieh, Satyajit Pradhan, William Small, Abhishek A Solanki

Faculty, Staff and Student Publications

Background: Radiation-related lymphopenia has been associated with suboptimal tumor control rates leading to inferior survival outcomes. To date, no standardized dose constraints are available to limit radiation dose to resident and circulating lymphocyte populations. We undertook this systemic review of the literature to provide a synopsis of the dosimetric predictors of radiation-related lymphopenia in solid malignancies.

Methodology: A systematic literature review of PubMed (National Institutes of Health), Cochrane Central (Cochrane collaboration), and Google Scholar was conducted with the following keywords: "radiation", "lymphopenia", "cancer", "dosimetric predictors" with an inclusion deadline of May 31, 2022. Studies that met prespecified inclusion criteria were …

Bcl11b And Atoh8 Coordinate Cellular Plasticity For Reprogramming And Transformation, Mo-Fan Huang, Rachel Shoemaker, Dung-Fang Lee

Faculty, Staff and Student Publications

By dissecting and comparing the transcriptional trajectories and epigenomic traits of reprogramming and transforming cells at the single-cell resolution, Huyghe et al discovered Bcl11b and Atoh8, two key transcription factors controlling cell plasticity during pluripotent reprogramming and oncogenic transformation.

Monitoring Pd-L1 Expression On Circulating Tumor-Associated Cells In Recurrent Metastatic Non-Small-Cell Lung Carcinoma Predicts Response To Immunotherapy With Radiation Therapy, Jillian A Moran, Daniel L Adams, Martin J Edelman, Pablo Lopez, Jianzhong He, Yawei Qiao, Ting Xu, Zhongxing Liao, Kirby P Gardner, Cha-Mei Tang, Steven H Lin

Faculty, Staff and Student Publications

Purpose: Current diagnostic methods to determine programmed death 1 (PD-1) receptor and its ligand (PD-L1)/PD-1 immunotherapy (immune checkpoint inhibitor [ICI]) efficacy in recurrent or metastatic non-small-cell lung carcinoma (rmNSCLC) are imprecise. Although previously shown that patients with high tumor PD-L1 (≥ 50%) demonstrate clinical benefit in the form of disease reduction and improved survival, patients with low PD-L1 (< 50%) sometimes benefit from treatment. Since the PD-L1/PD-1 pathway is dynamic, monitoring PD-L1 levels during treatment may be more accurate than a static baseline tumor biopsy; however, rebiopsying the primary or metastatic disease is rarely feasible. Liquid biopsies that measure the upregulation of PD-L1 on tumor-associated cells (TACs), ie, cancer-associated macrophage-like cells and circulating tumor cells, have been performed, but their predictive value for ICI therapy efficacy is unknown.

Materials and methods: We initiated a single-blind prospective study to evaluate TAC PD-L1 expression changes in rmNSCLC from blood samples before (T0) and after (T1) treatment with ICI (ICI, n = 41) or without ICI (no ICI, n = 41). Anonymized …

Association Of Apremilast With Vascular Inflammation And Cardiometabolic Function In Patients With Psoriasis: The Vip-A Phase 4, Open-Label, Nonrandomized Clinical Trial, Joel M Gelfand, Daniel B Shin, April W Armstrong, Stephen K Tyring, Andrew Blauvelt, Scott Gottlieb, Benjamin N Lockshin, Robert E Kalb, Robert Fitzsimmons, Justin Rodante, Philip Parel, Grigory A Manyak, Laurel Mendelsohn, Megan H Noe, Maryte Papadopoulos, Maha N Syed, Thomas J Werner, Joy Wan, Martin P Playford, Abass Alavi, Nehal N Mehta

Faculty, Staff and Student Publications

IMPORTANCE: Psoriasis is an inflammatory condition associated with metabolic and cardiovascular disease. Apremilast, a phosphodiesterase 4 inhibitor, is commonly used for psoriasis and can cause weight loss.

OBJECTIVE: To determine the association between apremilast and aortic vascular inflammation as assessed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), cardiometabolic markers (primary outcomes at week 16), and abdominal fat composition.

DESIGN, SETTING, AND PARTICIPANTS: A single-arm, open-label, interventional, nonrandomized clinical trial in which the imaging and laboratory outcomes were measured by an investigator who was blinded to time was conducted between April 11, 2017, and August 17, 2021, at 7 dermatology sites …