Medical Specialties Commons^™

Wide Range Of Phenotypic Severity In Individuals With Late Truncations Unique To The Predominant Cdkl5 Transcript In The Brain, Laura Keehan, Isabel Haviland, Yoel Gofin, Lindsay C Swanson, Christelle Moufawad El Achkar, John Schreiber, Grace E Vannoy, Emily O'Heir, Anne O'Donnell-Luria, Richard Alan Lewis, Pilar Magoulas, Alyssa Tran, Mahshid S Azamian, Hsiao-Tuan Chao, Lisa Pham, Rodney C Samaco, Sarah Elsea, Erin Thorpe, Akanchha Kesari, Denise Perry, Brendan Lee, Seema R Lalani, Jill A Rosenfeld, Heather E Olson, Lindsay C Burrage

Faculty, Staff and Students Publications

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is caused by heterozygous or hemizygous variants in CDKL5 and is characterized by refractory epilepsy, cognitive and motor impairments, and cerebral visual impairment. CDKL5 has multiple transcripts, of which the longest transcripts, NM_003159 and NM_001037343, have been used historically in clinical laboratory testing. However, the transcript NM_001323289 is the most highly expressed in brain and contains 170 nucleotides at the 3' end of its last exon that are noncoding in other transcripts. Two truncating variants in this region have been reported in association with a CDD phenotype. To clarify the significance and range …

Baseline Microperimetry And Oct In The Rush2a Study: Structure-Function Association And Correlation With Disease Severity, Eleonora M Lad, Jacque L Duncan, Wendi Liang, Maureen G Maguire, Allison R Ayala, Isabelle Audo, David G Birch, Joseph Carroll, Janet K Cheetham, Todd A Durham, Abigail T Fahim, Jessica Loo, Zengtian Deng, Dibyendu Mukherjee, Elise Heon, Robert B Hufnagel, Bin Guan, Alessandro Iannaccone, Glenn J Jaffe, Christine N Kay, Michel Michaelides, Mark E Pennesi, Ajoy Vincent, Christina Y Weng, Sina Farsiu

Faculty, Staff and Students Publications

PURPOSE: To investigate baseline mesopic microperimetry (MP) and spectral domain optical coherence tomography (OCT) in the Rate of Progression in USH2A-related Retinal Degeneration (RUSH2A) study.

DESIGN: Natural history study METHODS: Setting: 16 clinical sites in Europe and North AmericaStudy Population: Participants with Usher syndrome type 2 (USH2) (N = 80) or autosomal recessive nonsyndromic RP (ARRP) (N = 47) associated with biallelic disease-causing sequence variants in USH2AObservation Procedures: General linear models were used to assess characteristics including disease duration, MP mean sensitivity and OCT intact ellipsoid zone (EZ) area. The associations between mean sensitivity and EZ area with other measures, …

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 …

Autologous Humanized Mouse Models To Study Combination And Single-Agent Immunotherapy For Colorectal Cancer Patient-Derived Xenografts, Preeti Kanikarla Marie, Alexey V Sorokin, Lea A Bitner, Rebecca Aden, Michael Lam, Ganiraju Manyam, Melanie N Woods, Amanda Anderson, Anna Capasso, Natalie Fowlkes, Michael J Overman, David G Menter, Scott Kopetz

Faculty, Staff and Student Publications

Designing studies of immunotherapy is limited due to a lack of pre-clinical models that reliably predict effective immunotherapy responses. To address this gap, we developed humanized mouse models of colorectal cancer (CRC) incorporating patient-derived xenografts (PDX) with human peripheral blood mononuclear cells (PBMC). Humanized mice with CRC PDXs were generated via engraftment of autologous (isolated from the same patients as the PDXs) or allogeneic (isolated from healthy donors) PBMCs. Human T cells were detected in mouse blood, tissues, and infiltrated the implanted PDXs. The inclusion of anti-PD-1 therapy revealed that tumor responses in autologous but not allogeneic models were more …

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.

Mathematical Modeling Of Cancer Immunotherapy For Personalized Clinical Translation, Joseph D Butner, Prashant Dogra, Caroline Chung, Renata Pasqualini, Wadih Arap, John Lowengrub, Vittorio Cristini, Zhihui Wang

Faculty, Staff and Student Publications

Encouraging advances are being made in cancer immunotherapy modeling, especially in the key areas of developing personalized treatment strategies based on individual patient parameters, predicting treatment outcomes and optimizing immunotherapy synergy when used in combination with other treatment approaches. Here we present a focused review of the most recent mathematical modeling work on cancer immunotherapy with a focus on clinical translatability. It can be seen that this field is transitioning from pure basic science to applications that can make impactful differences in patients' lives. We discuss how researchers are integrating experimental and clinical data to fully inform models so that …

Which Children Are Frequently Victimized In Us Elementary Schools? Population-Based Estimates, Paul L Morgan, Adrienne D Woods, Yangyang Wang, George Farkas, Yoonkyung Oh, Marianne M Hillemeier, Cynthia Mitchell

Faculty, Staff and Student Publications

We analyzed a population-based cohort of 11,780 U.S. kindergarten children to identify risk and protective factors predictive of frequent verbal, social, reputational, and/or physical bullying victimization during the upper elementary grades. We also stratified the analyses by biological sex. Both girls and boys displaying kindergarten externalizing problem behaviors were at consistently higher risk of frequent victimization during 3rd-5th grade (for the combined sample of boys and girls, verbal odds ratio [OR] = 1.82, social OR = 1.60, reputational OR = 1.85, physical OR = 1.67, total OR = 1.93). Hispanic children relative to non-Hispanic White children and those from higher …

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 …

Remodeling Of The Plasma Membrane By Surface-Bound Protein Monomers And Oligomers: The Critical Role Of Intrinsically Disordered Regions, Mussie K Araya, Yong Zhou, Alemayehu A Gorfe

Faculty, Staff and Student Publications

The plasma membrane (PM) of cells is a dynamic structure whose morphology and composition is in constant flux. PM morphologic changes are particularly relevant for the assembly and disassembly of signaling platforms involving surface-bound signaling proteins, as well as for many other mechanochemical processes that occur at the PM surface. Surface-bound membrane proteins (SBMP) require efficient association with the PM for their function, which is often achieved by the coordinated interactions of intrinsically disordered regions (IDRs) and globular domains with membrane lipids. This review focuses on the role of IDR-containing SBMPs in remodeling the composition and curvature of the PM. …

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 …

Inpatient Teleneurology Follow-Up Has Comparable Outcomes To In-Person Neurology Follow-Up, Alicia M Zha, Alyssa D Trevino, Christy M Ankrom, Kristie M Chu, Michele M Joseph, Tushar Patni, Tiffany D Cossey, Sean I Savitz, Tzu-Ching Wu, Amanda Jagolino-Cole

Faculty, Staff and Student Publications

Background and Objectives

Community emergency departments often transfer patients for lack of neurology coverage, potentially burdening patients and accepting facilities. Telestroke improves access to acute stroke care, but there is a lack of data on inpatient teleneurology and telestroke care.

Methods

From our prospective telestroke registry, we retrospectively reviewed 3702 consecutive patients who were seen via telestroke between September 2015 and December 2018. Patients who required transfer after initial telestroke evaluation or who were kept at hospitals without consistent neurology coverage were excluded from analysis. We compared baseline demographics, clinical characteristics, and hospital outcomes in patients who were subsequently followed …

Predictors For Outcomes Of Noninvasive, Individualized Transcranial Magnetic Neuromodulation In Multiple Sclerosis Women With Neurogenic Voiding Dysfunction, Yongchang Jang, Khue Tran, Zhaoyue Shi, Karmonik Christof, Darshil Choksi, Betsy H Salazar, John A Lincoln, Rose Khavari

Faculty, Staff and Student Publications

Purpose:

Multiple sclerosis (MS) is a multifocal demyelinating disease that affects the central nervous system (CNS) and commonly leads to neurogenic lower urinary tract dysfunction (NLUTD). Proper storage and release of urine relies on synchronized activity of the LUT, which is meticulously regulated by supraspinal circuits, making it vulnerable to diseases such as MS. NLUTD, characterized by voiding dysfunction (VD), storage issues, or a combination of both is a common occurrence in MS. Unfortunately, there are limited treatment options for NLUTD, making the search for alternative treatments such as transcranial rotating permanent magnet stimulation (TRPMS) of utmost importance. To assess …

Extensive Accumulation Of Misfolded Protein Aggregates During Natural Aging And Senescence, Karina Cuanalo-Contreras, Jonathan Schulz, Abhisek Mukherjee, Kyung-Won Park, Enrique Armijo, Claudio Soto

Faculty, Staff and Student Publications

Accumulation of misfolded protein aggregates is a hallmark event in many age-related protein misfolding disorders, including some of the most prevalent and insidious neurodegenerative diseases. Misfolded protein aggregates produce progressive cell damage, organ dysfunction, and clinical changes, which are common also in natural aging. Thus, we hypothesized that aging is associated to the widespread and progressive misfolding and aggregation of many proteins in various tissues. In this study, we analyzed whether proteins misfold, aggregate, and accumulate during normal aging in three different biological systems, namely senescent cells,

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 …

Fast Does Not Imply Flawed: Analyzing Emergency Physician Productivity And Medical Errors, Nathan R Hoot, Timothy J Barbosa, Hei Kit Chan, Jonathan G Rogg

Faculty, Staff and Student Publications

OBJECTIVE: To determine whether emergency physician productivity is associated with the risk of medical errors.

METHODS: We retrospectively analyzed quality assurance (QA) and billing data over 3 years at 2 urban emergency departments. Faculty physicians working 400 hours or more at either site were included. We measured physician years of experience, age, gender, patients seen per hour (PPH), and relative value units billed per hour (RVU/h). From an established QA process, we obtained adjudicated medical errors to calculate rates of medical errors per 1000 patients seen as the outcome. We discretized numeric variables and used Kruskal-Wallis testing to examine relationships …

Endovascular Repair Of Intercostal Patch Aneurysms In A Patient With Loyes-Dietz Syndrome, Guilherme B Lima, Laura Ocasio, Marina Dias-Neto, Emanuel R Tenorio, Thanila A Macedo, Gustavo S Oderich

Faculty, Staff and Student Publications

No abstract provided.

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 …

Synergic Effect Of Cai And Lii On Ionic Conductivity Of Solution-Based Synthesized Li7p3s11 Solid Electrolyte, Binoy Yohannan, Allen C Omo-Ogboi, Varaha S Tammisetti, Adan Rios

Faculty, Staff and Student Publications

Autoimmune hepatitis (AIH) is a rare immune-mediated disease predominantly seen in women and triggered by various environmental factors. Rarely, AIH can be triggered by an underlying malignancy. We report a woman in her 60s who presented with markedly abnormal liver biochemical tests. Serology was positive for anti-smooth muscle antibodies and a liver biopsy confirmed AIH. During the hospital course, she developed sepsis and acute renal failure requiring dialysis support. Serum protein electrophoresis (SPEP) showed a monoclonal IgG kappa protein of 1.92 g/dL and a bone marrow biopsy revealed 7% clonal plasma cells. She had lytic lesions on skeletal survey confirming …

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) …

Luspatercept In Low-Risk Myelodysplastic Syndrome: A Real-World Single Institution Case Series, Shamis Khan, Sara Taveras Alam, Rosa Torres Ramos, John Etumbani Mbue, Effrosyni Apostolidou, Gustavo A Rivero, Sarvari Venkata Yellapragada

Faculty, Staff and Student Publications

No abstract provided.

Heterogeneous Nuclear Ribonucleoprotein K Is Overexpressed In Acute Myeloid Leukemia And Causes Myeloproliferation In Mice Via Altered, Marisa J L Aitken, Prerna Malaney, Xiaorui Zhang, Shelley M Herbrich, Lauren Chan, Oscar Benitez, Ashley G Rodriguez, Huaxian Ma, Rodrigo Jacamo, Ruizhi Duan, Todd M Link, Steven M Kornblau, Rashmi Kanagal-Shamanna, Carlos E Bueso-Ramos, Sean M Post

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) is driven by numerous molecular events that contribute to disease progression. Herein, we identify hnRNP K overexpression as a recurrent abnormality in AML that negatively correlates with patient survival. Overexpression of hnRNP K in murine fetal liver cells results in altered self-renewal and differentiation potential. Further, murine transplantation models reveal that hnRNP K overexpression results in myeloproliferation in vivo. Mechanistic studies expose a direct functional relationship between hnRNP K and RUNX1—a master transcriptional regulator of hematopoiesis often dysregulated in leukemia. Molecular analyses show that overexpression of hnRNP K results in an enrichment of an …

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: …