Medicine and Health Sciences Commons^™

Survival Analysis Of Clear Cell Renal Cell Carcinoma Based On Radiomics And Deep Learning Features From Ct Images, Zhennan Lu, Sijia Wu, Dan Ni, Meng Zhou, Tao Wang, Xiaobo Zhou, Liyu Huang, Yu Yan

Faculty, Staff and Student Publications

Purpose: To create a nomogram for accurate prognosis of patients with clear cell renal cell carcinoma (ccRCC) based on computed tomography images.

Methods: Eight hundred twenty-two ccRCC patients with contrast-enhanced computed tomography images involved in this study were collected. A rectangular region of interest surrounding the tumor was used to extract quantitative radiomics and deep-learning features, which were filtered by Cox proportional hazard regression model and least absolute shrinkage and selection operator. Then the selected features formed a fusion signature, which was assessed by Cox proportional hazard regression model method, Kaplan-Meier analysis, receiver operating characteristic curves, and concordance index (C-index) …

Retrospective Derivation Of A Causal Pathway For Diabetic Ketoacidosis In Adult Patients With Type 2 Diabetes Mellitus, Jeffrey A Kline, Nicholas A Wesner, Amina T Sharif, Richard T Griffey, Phillip D Levy, Robert D Welch, George Grunberger

2020-Current year OA Pubs

BACKGROUND: Type 2 ketone-prone diabetes mellitus (T2KPDM) is thought to occur in men of African descent, with obesity who experienced prolonged hyperglycemia; the role of medication non-adherence as a contributing cause remains unstudied.

RESEARCH DESIGN AND METHODS: This was a retrospective study of unique adults (>18 years) who sought emergency care one of four hospitals in the greater Detroit area. Patients were identified on the basis of a laboratory order for a ß-hydroxybutyrate concentration. Two research coordinators abstracted 119 data fields. Patients were divided into four phenotypes: (1) no prior DM, (2) type 2 DM without prior ketosis, (3) …

Assessing Tolerability With The Functional Assessment Of Cancer Therapy Item Gp5: Psychometric Evidence From Libretto-531, A Phase 3 Trial Of Selpercatinib In Medullary Thyroid Cancer, Antoine Regnault, Laurine Bunod, Angely Loubert, Marcia S. Brose, Lisa M. Hess, Patricia Maeda, Yan Lin, Rebecca M. Speck, Adrienne M. Gilligan, Nalin Payakachat

Department of Medical Oncology Faculty Papers

BACKGROUND: This psychometric analysis generated evidence to support the use of the Functional Assessment of Cancer Therapy item GP5 (GP5) as a measure of tolerability and confirms the appropriateness of categorizing "high side-effect burden" using a rating of 3 or 4 (score ranges 0-4) in patients with advanced/metastatic RET-mutant medullary thyroid cancer (MTC).

METHODOLOGY: Blinded, pooled interim data from the safety population (n=290) enrolled in the phase 3 LIBRETTO-531 trial (NCT04211337) were used. Intraclass correlation coefficients (ICC) were calculated for test-retest reliability using data from cycles 1-2 post-baseline. Construct validity was evaluated by examining the correlations of GP5 ratings with …

Deuterated Water Labeling In Ibrutinib-Treated Patients With Cll: Leukemia Cell Kinetics Correlate With Ighv, Zap-70, And Mrd, Ekaterina Kim, Shih-Shih Chen, Mariela Sivina, Hyunsoo Hwang, Xuelin Huang, Alessandra Ferrajoli, Nitin Jain, William G Wierda, Dominik Wodarz, Nicholas Chiorazzi, Jan A Burger

Faculty, Staff and Student Publications

Deuterated (“heavy”) water labeling in patients with chronic lymphocytic leukemia (CLL) demonstrates that IGHV unmutated and ZAP-70+ patients have higher blood and tissue CLL death rates on ibrutinib therapy, resulting in lower measurable residual disease levels with long-term ibrutinib treatment. This trial was registered at www.clinicaltrials.gov as #NCT01752426.

The Effect Of A Low-Carbohydrate Diet On Evoked Pain And Quality Of Life In Non-Hispanic Black Women With Knee Osteoarthritis: A Pilot Study, Asia M Wiggins, Larissa J Strath, Gray E Mcpherson, Barbara A Gower, Amy M Goss, Burel R Goodin, Robert E Sorge

2020-Current year OA Pubs

BACKGROUND: Knee osteoarthritis (KOA) is a prevalent chronic pain condition that can significantly impact quality of life and contribute to recognized chronic pain racial disparities. We have shown that a low-carbohydrate diet (LCD) can reduce KOA-related pain. Our previous work suggested that the LCD was more beneficial for women and non-Hispanic Black (NHB) adults, but our sample was not sufficiently diverse. Thus, we sought to determine whether the LCD may be beneficial for NHB women with KOA on measures of self-reported and evoked pain.

METHODS: Fourteen NHB women (M = 55.93, S.D. = 7.79 years of age) with KOA were …

Transforming Growth Factor-Beta Is Increased In Sputum From Individuals With Rheumatoid Arthritis-Associated Pulmonary Fibrosis, Timothy M. Wilson, Matthew Bolt, Andrew Stahly, Joyce S. Lee, Tami J. Bang, Peter B. Sachs, Kevin D. Deane, Stephen M. Humphries, Joshua J. Solomon, M. Kristen Demoruelle

Division of Rheumatology Faculty Papers

BACKGROUND: Interstitial lung disease (ILD) develops in 5-10% of patients with RA and contributes significantly to morbidity and mortality, particularly in those with a fibrotic phenotype. Yet, biomarkers to reliably identify RA patients with underlying pulmonary fibrosis are inadequate. Herein, we used sputum to identify lung-based biomarkers that distinguish RA patients with underlying pulmonary fibrosis and may better inform underlying pathogenesis in RA-ILD.

METHODS: We included 37 RA patients with pulmonary fibrosis (RA-PF) and 30 RA patients without ILD (RA-no-ILD). Induced sputum and serum were tested for TGF-β levels by immunoassay. DNA was extracted to determine presence of the MUC5B …

Centering Autonomy And Choice To Support Oral Prep Utilization Among People Who Inject Drugs: Qualitative Lessons From Hptn 094 Integra, Amaya Perez-Brumer, Rose Schmidt, Rebecca Kennedy, Jordan E Lake, Yolanda R Villarreal, Sydney Bornstein, Irene Kuo, Omar Nieto, Julie Franks, Cecile Denis, Nabila El-Bassel, Steve Shoptaw, Peter Davidson, Laramie R Smith

Faculty, Staff and Student Publications

Background: Oral Pre-exposure prophylaxis (PrEP) is effective in preventing HIV transmission. However, despite high rates of HIV risk behaviors among people who inject drugs (PWID), this population remains underserved by current HIV prevention efforts in the United States. To address this challenge, we conducted an in-depth exploration of perspectives on using oral PrEP among PWID engaged in the HIV Prevention Trials Network (HPTN) 094 INTEGRA Study.

Methods: Guided by the Practical, Robust, Implementation, and Sustainability Model (PRISM), our qualitative study drew on semi-structured interviews conducted as part of the embedded implementation science evaluation of HPTN 094 INTEGRA. Seventy-seven PWID participants …

Transcriptomic Clustering Of Chronic Lymphocytic Leukemia: Molecular Subtypes Based On Bruton’S Tyrosine Kinase Expression Levels, Gorkem Kismali, Ganiraju Manyam, Nitin Jain, Cristina Ivan, Betty Lamothe, Mary L Ayres, Lakesla R Iles, William G Wierda, Varsha Gandhi

Faculty, Staff and Student Publications

Historically, CLL prognostication relied on disease burden, reflected in clinical stage. Later, chromosome abnormalities and genomics suggested several CLL subtypes which were aligned with response to therapy. Gene expression profiling data identified pathways associated with CLL progression. We hypothesized that transcriptome and proteome may identify functional omics associated with CLL nosology. As a test cohort, we utilized publicly available treatment-naïve CLL transcriptomics data (n = 130) and did consensus clustering that identified BTK-expression-based clusters. The BTK-High and BTK-Low clusters were validated in public and our in-house databases (n = >550 CLL patients). To associate with functional relevance, we took samples …

Utility Of Colposcopy For The Screening And Management Of Cervical Cancer In Africa: A Cross-Sectional Analysis Of Providers’ Training And Practices, Joël Fokom Domgue, Issimouha Dille, Freddy Gnangnon, Sharon Kapambwe, Celine Bouchard, Nomonde Mbatani, Elodie Gauroy, Nathalie Ledaga Ambounda, Robert Yu, Fatoumata Sidibe, Joseph Kamgno, Bangaly Traore, Pierre-Marie Tebeu, Gregory Halle-Ekane, Mohenou Isidore Diomande, Jean-Marie Dangou, Fabrice Lecuru, Isaac Adewole, Marie Plante, Partha Basu, Sanjay Shete

Faculty, Staff and Student Publications

Introduction: Cervical cancer is a public health issue in Africa with devastating socioeconomic consequences due to the lack of organized screening programs. The success of screening programs depends on the appropriate investigation and management of women who test positive for screening. Colposcopic assessment following positive screening results is a noteworthy issue in Africa. This study aimed to assess the utilization of colposcopy by providers in the region.

Methods: A cross-sectional study was conducted in 2021-2022 among healthcare providers involved in cervical cancer prevention activities in Africa. They were invited to report prior colposcopy training, whether they performed colposcopy and the …

Primary Anorectal Mammary-Like Adenocarcinoma: A Potential Diagnostic Pitfall With Conventional Colorectal Adenocarcinoma, Margaret L Axelrod, Xiuli Liu, Pooja Navale

2020-Current year OA Pubs

Anogenital mammary-like glands (AGMLGs) are present in the anogenital region that bear striking morphologic and protein-expression similarities to mammary glands in the breast. AGMLGs can give rise to both benign and malignant lesions which mimic primary breast lesions. Herein, we report two mammary-type adenocarcinomas arising from AGMLGs, including one in the previously unreported site of the rectum. Recognition of mammary-type adenocarcinoma in the rectal and anogenital regions is crucial as clinical management options may differ compared to conventional colorectal adenocarcinomas.

Pathways From Socioeconomic Factors To Major Cardiovascular Events Among Postmenopausal Veteran And Nonveteran Women: Findings From The Women's Health Initiative, Hind A Beydoun, May A Beydoun, Rebecca L Kinney, Simin Liu, Rona Yu, Matthew Allison, Robert B Wallace, Qian Xiao, Longjian Liu, Philippe Gradidge, Su Yon Jung, Hilary A Tindle, Shawna Follis, Robert Brunner, Jack Tsai

Faculty, Staff and Student Publications

BACKGROUND: Cardiovascular disease (CVD) remains a leading cause of death for women in the United States, with veterans being at potentially higher risk than their nonveteran counterparts due to accelerated aging and distinct biopsychosocial mechanisms. We examined pathways between selected indicators of socioeconomic status (SES) such as education, occupation, household income, and neighborhood SES and major CVD events through lifestyle and health characteristics among veteran and nonveteran postmenopausal women.

METHODS AND RESULTS: A total of 121 286 study-eligible WHI (Women's Health Initiative) participants (3091 veterans and 118 195 nonveterans) were prospectively followed for an average of 17 years, during which …

Clover (Clostridium Difficile Vaccine Efficacy Trial) Study: A Phase 3, Randomized Trial Investigating The Efficacy And Safety Of A Detoxified Toxin A/B Vaccine In Adults 50 Years And Older At Increased Risk Of Clostridioides Difficile Infection, Curtis J Donskey, Erik R Dubberke, Et Al.

2020-Current year OA Pubs

BACKGROUND: Clostridioides difficile infection (CDI) causes substantial mortality and healthcare burden. We assessed the detoxified toxin-A/B PF-06425090 vaccine for primary CDI prevention.

METHODS: This phase 3 observer-blinded study randomized (1:1) ≥50-year-olds at increased CDI risk (N = 17 535) to receive 3 PF-06425090 or placebo doses (0, 1, and 6 months). Primary end points were first CDI episode (≥3 unformed stools within 24 hours; central laboratory-confirmed toxin A/B positive) ≥14 days post-dose 3 (PD3; first primary) and post-dose 2 (PD2; second primary). CDI duration, need for CDI-related medical attention (secondary end points), and antibiotic use (post hoc analysis) PD3 were …

Correlation Of Genogroup I, Genotype 1 (Gi.1) Norovirus Neutralizing Antibody Levels With Gi.1 Histo-Blood Group Antigen-Blocking Antibody Levels, Robert L Atmar, Khalil Ettayebi, Frederick H Neill, Ralph P Braun, James Sherwood, Sasirekha Ramani, Mary K Estes

Faculty, Staff and Students Publications

Background: The in vitro cultivation of human noroviruses allows a comparison of antibody levels measured in neutralization and histo-blood group antigen (HBGA)-blocking assays.

Methods: Serum samples collected during the evaluation of an investigational norovirus vaccine (HIL-214 [formerly TAK-214]) were assayed for neutralizing antibody levels against the vaccine's prototype Norwalk virus/genogroup I, genotype 1 (GI.1) (P1) virus strain. Results were compared with those previously determined using HBGA-blocking assays.

Results: Neutralizing antibody seroresponses were observed in 83% of 24 vaccinated adults, and antibody levels were highly correlated (r = 0.81; P < .001) with those measured by HBGA blocking.

Conclusions: Genogroup I, genotype 1 (GI.1)-specific HBGA-blocking antibodies are a surrogate …

First-In-Human Dose-Escalation Study Of Fianlimab, An Antilymphocyte Activation Gene-3 Antibody, With Cemiplimab In Patients With Advanced Malignancies, Nehal J Lakhani, Haeseong Park, Et Al.

2020-Current year OA Pubs

PURPOSE: Preclinical data indicate that fianlimab (antilymphocyte activation gene-3) plus cemiplimab (anti-PD-1) enhances antitumor activity. Here, we report prespecified final analyses of the dose-escalation part of a first-in-human, phase 1 study (NCT03005782) of fianlimab as monotherapy and in combination with cemiplimab in patients with advanced malignancies.

PATIENTS AND METHODS: Adult patients received 1 to 40 mg/kg of fianlimab plus 350 mg of cemiplimab every 3 weeks (Q3W) across various dose-escalation schedules. Primary objectives were the rate of dose-limiting toxicities, adverse events (including immune mediated), deaths, laboratory abnormalities, and pharmacokinetics. Secondary outcomes were objective response rate, best overall response, duration of …

Development, Progression, And Mortality Of Suspected Interstitial Lung Disease In Copdgene, Jonathan A Rose, Ann-Marcia C Tukpah, Claire Cutting, Noriaki Wada, Mizuki Nishino, Matthew Moll, Sean Kalra, Bina Choi, David A Lynch, Benjamin A Raby, Ivan O Rosas, Raúl San José Estépar, George R Washko, Edwin K Silverman, Michael H Cho, Hiroto Hatabu, Rachel K Putman, Gary M Hunninghake

Faculty, Staff and Students Publications

Rationale: Some with interstitial lung abnormalities (ILA) are suspected to have interstitial lung disease (ILD), a subgroup with adverse outcomes. Rates of development and progression of suspected ILD and their effect on mortality are unknown. Objectives: To determine rates of development, progression, and mortality in those with suspected ILD and assess effects of individual ILD and progression criteria.

Methods: Participants from COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) with ILA characterization and FVC at enrollment and 5-year follow-up were included. ILD was defined as ILA and fibrosis and/or FVC < 80% predicted. Prevalent ILD was assessed at enrollment and incident ILD and progression were assessed at 5-year follow-up. Computed tomography (CT) progression was assessed visually and FVC decline as relative change. Multivariable Cox regression tested associations between mortality and prevalent ILD, incident ILD, and progression groups.

Measurements and Main Results: Of 9,588 participants at enrollment, 268 …

Global Impact Of Aging On The Hemodynamic Response Function In The Gray Matter Of Human Cerebral Cortex, Nooshin J Fesharaki, Amanda Taylor, Keisjon Mosby, Ruosha Li, Jung Hwan Kim, David Ress

Faculty, Staff and Students Publications

In functional magnetic resonance imaging, the hemodynamic response function (HRF) is a stereotypical response to local changes in cerebral hemodynamics and oxygen metabolism due to briefly (< 4 s) evoked neural activity. Accordingly, the HRF is often used as an impulse response with the assumption of linearity in data analysis. In cognitive aging studies, it has been very common to interpret differences in brain activation as age-related changes in neural activity. Contrary to this assumption, however, evidence has accrued that normal aging may also significantly affect the vasculature, thereby affecting cerebral hemodynamics and metabolism, confounding interpretation of fMRI cognitive aging studies. In this study, use was made of a multisensory task to evoke the HRF in ~87% of cerebral cortex in cognitively intact adults with ages ranging from 22 to 75 years. This widespread activation enabled us to investigate age trends in the spatial distributions of HRF characteristics within the majority of cortical gray matter, which we termed as global age trends. The task evoked both positive and negative HRFs, which were characterized using model-free parameters in native-space coordinates. We found significant global age trends in the distributions of HRF parameters in terms of both amplitudes (e.g., peak amplitude and contrast-to-noise ratio) and temporal dynamics (e.g., full-width-at-half-maximum). Our findings offer insight into how age-dependent changes affect neurovascular coupling and show promise for use of HRF parameters as non-invasive indicators for age-related pathology.

Parent And Primary Care Clinician Perceptions About Pediatric Hypertension, Abbas H. Zaidi, Erica Sood, Sarah De Ferranti, Samuel Gidding, Varsha Zadokar, Jonathan Miller, Anne Kazak

Department of Pediatrics Faculty Papers

IMPORTANCE: Despite published guidelines and a prevalence of pediatric hypertension of approximately 3%, less than 25% of affected children are identified, with 60% not receiving any intervention despite detection. Understanding the knowledge and perceptions of parents or caregivers and health care teams is crucial to identify factors that may contribute to these unacceptably low detection rates.

OBJECTIVE: To examine the knowledge and perceptions of parents and health care teams regarding pediatric hypertension to identify common themes contributing to low hypertension detection.

DESIGN, SETTING, AND PARTICIPANTS: This qualitative study, interviewed parents of children diagnosed with hypertension who did not follow up …

Estimation Of Prevalence Of Autoimmune Diseases In The United States Using Electronic Health Record Data, Aaron H. Abend, Albert M. Lai, Et Al.

2020-Current year OA Pubs

BACKGROUNDPrevious epidemiologic studies of autoimmune diseases in the US have included a limited number of diseases or used metaanalyses that rely on different data collection methods and analyses for each disease.METHODSTo estimate the prevalence of autoimmune diseases in the US, we used electronic health record data from 6 large medical systems in the US. We developed a software program using common methodology to compute the estimated prevalence of autoimmune diseases alone and in aggregate that can be readily used by other investigators to replicate or modify the analysis over time.RESULTSOur findings indicate that over 15 million people, or 4.6% of …

Mexican Health And Aging Study Biomarker And Genetic Data Profile, Rafael Samper-Ternent, Jesús Daniel Zazueta-Borboa, Alejandra Michaels-Obregon, Dolly Reyes-Dumeyer, Sandra Barral, Giuseppe Tosto, Rebeca Wong

Faculty, Staff and Student Publications

The Mexican Health and Aging Study (MHAS) is one of the largest ongoing longitudinal studies of aging in Latin America, with six waves over 20 years. MHAS includes sociodemographic, economic, and health data from a nationally representative sample of adults 50 years and older in urban and rural Mexico. MHAS is designed to study the impact of diseases on adults' health, function, and mortality. As Mexico is experiencing rapid population aging, providing adequate information to study this phenomenon is vital for designing and implementing public policies. The availability of biomarker and genetic data and longitudinal survey data elevates opportunities for …

Diversity And Characteristics Of The Oral Microbiome Associated With Self-Reported Ancestral/Ethnic Groups, Qingguo Wang, Bing-Yan Wang, She'neka Williams, Hua Xie

Faculty, Staff and Student Publications

Periodontitis disproportionately affects genetic ancestral/ethnic groups. To characterize the oral microbiome from different genetic ancestral/ethnic groups, we collected 161 dental plaque samples from self-identified African Americans (AAs), Caucasian Americans (CAs), and Hispanic Americans (HAs) with clinical gingival health or biofilm-induced gingivitis on an intact periodontium. DNA was extracted from these samples, and then DNA libraries were prepared and sequenced using an Illumina NovaSeq high-throughput sequencer. We found significant differences in the diversity and abundance of microbial taxa among dental plaque samples of the AA, CA, and HA groups. We also identified unique microbial species in a self-reported ancestral/ethnic group. Moreover, …

Guideline-Directed Medical Therapy After Hospitalization For Acute Heart Failure: Insights From The Connect-Hf, Satoshi Shoji, Lisa Kaltenbach, Bradi B. Granger, Gregg C. Fonarow, Hussein R. Al-Khalidi, Nancy M. Albert, Javed Butler, Larry A. Allen, David E. Lanfear, Jennifer T. Thibodeau, Brittany M. Chapman, Sandra M. Oliver-Mcneil, G. Michael Felker, Ileana L. Piña, Christopher B. Granger, Adrian F. Hernandez, Adam D. Devore

Division of Cardiology Faculty Papers

BACKGROUND: Significant gap remains in the implementation of guideline-directed medical therapy (GDMT) in patients with heart failure after a hospitalization. We aimed to evaluate the use and titration of GDMT at discharge and over a 12-month period after hospital discharge and to identify factors associated with GDMT use and titration.

METHODS AND RESULTS: The CONNECT-HF (Care Optimization Through Patient and Hospital Engagement Clinical Trial for Heart Failure) trial evaluated the effect of a hospital and postdischarge quality improvement intervention in participants with heart failure with reduced ejection fraction. In this secondary analysis, we examined use and titration to at least …

Clinical Use Of Bedside Portable Ultra-Low-Field Brain Magnetic Resonance Imaging In Patients On Extracorporeal Membrane Oxygenation: Results From The Multicenter Safe Mri Ecmo Study, Sung-Min Cho, Shivalika Khanduja, Christopher Wilcox, Kha Dinh, Jiah Kim, Jin Kook Kang, Ifeanyi David Chinedozi, Zachary Darby, Matthew Acton, Hannah Rando, Jessica Briscoe, Errol L Bush, Haris I Sair, John Pitts, Lori R Arlinghaus, Audrey-Carelle N Wandji, Elena Moreno, Glenda Torres, Bindu Akkanti, Jose Gavito-Higuera, Steven Keller, Huimahn A Choi, Bo Soo Kim, Aaron Gusdon, Glenn J Whitman

Faculty, Staff and Student Publications

Background: Early detection of acute brain injury (ABI) at the bedside is critical in improving survival for patients with extracorporeal membrane oxygenation (ECMO) support. We aimed to examine the safety of ultra-low-field (ULF; 0.064-T) portable magnetic resonance imaging (pMRI) in patients undergoing ECMO and to investigate the ABI frequency and types with ULF-pMRI.

Methods: This was a multicenter prospective observational study (SAFE MRI ECMO study [Assessing the Safety and Feasibility of Bedside Portable Low-Field Brain Magnetic Resonance Imaging in Patients on ECMO]; NCT05469139) from 2 tertiary centers (Johns Hopkins, Baltimore, MD and University of Texas-Houston) with specially trained intensive …

Impact Of Prior Inotuzumab Ozogamicin Treatment On Brexucabtagene Autoleucel Outcomes In Adults With B-Cell All, Ibrahim Aldoss, Gregory W Roloff, Rawan Faramand, Noam E Kopmar, Chenyu Lin, Anjali S Advani, Simone E Dekker, Vishal K Gupta, Timothy E O'Connor, Nikeshan Jeyakumar, Ibrahim N Muhsen, Yannis Valtis, Amy Zhang, Katharine Miller, Katherine Sutherland, Kaitlyn C Dykes, Mohamed Ahmed, Evan Chen, Hector Zambrano, Danielle Bradshaw, Santiago Mercadal, Marc Schwartz, Sean Tracy, Bhagirathbhai Dholaria, Michal Kubiak, Akash Mukherjee, Navneet Majhail, Minoo Battiwalla, Luke Mountjoy, Shahbaz A Malik, John Mathews, Paul Shaughnessy, Aaron C Logan, Abdullah Ladha, Maryann Stefan, Caitlin Guzowski, Rasmus T Hoeg, Talal Hilal, Jozal Moore, Matthew Connor, Kristen M O'Dwyer, Laquisa C Hill, Stephanie B Tsai, Joshua Sasine, Melhem M Solh, Catherine J Lee, Vamsi K Kota, Divya Koura, Muthu Veeraputhiran, Betsy Blunk, Caspian Oliai, Jessica T Leonard, Noelle V Frey, Jae H Park, Marlise R Luskin, Veronika Bachanova, Ahmed Galal, Michael R Bishop, Wendy Stock, Ryan D Cassaday, Vinod Pullarkat, Bijal D Shah, Lori S Muffly

Faculty, Staff and Students Publications

The effect of prior inotuzumab ozogamicin (InO) treatment on brexucabtagene autoleucel (brexu-cel) outcomes remains unclear in adults with acute lymphoblastic leukemia (ALL). We conducted a retrospective multicenter analysis of 189 patients with relapsed/refractory ALL treated with brexu-cel. Over half of the patients received InO before brexu-cel (InO exposed). InO-exposed patients were more heavily pretreated (P = .02) and frequently had active marrow disease before apheresis (P = .03). Response rate and toxicity profile after brexu-cel were comparable for InO-exposed and InO-naïve patients; however, consolidation therapy after brexu-cel response was used at a higher rate in InO-naïve patients (P = .005). …

Imlunestrant, An Oral Selective Estrogen Receptor Degrader, As Monotherapy And In Combination With Targeted Therapy In Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Phase Ia/Ib Ember Study, Komal L Jhaveri, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

PURPOSE: Imlunestrant is a next-generation oral selective estrogen receptor (ER) degrader designed to deliver continuous ER target inhibition, including in

METHODS: An i3+3 dose-escalation design was used, followed by dose expansions of imlunestrant as monotherapy or in combination with abemaciclib with or without aromatase inhibitor (AI), everolimus, or alpelisib. Imlunestrant was administered orally once daily and with the combination partner per label.

RESULTS: Overall, 262 patients with ER+/HER2- ABC were treated (phase Ia, n = 74; phase Ib, n = 188). Among patients who received imlunestrant monotherapy (n = 114), no dose-limiting toxicities or discontinuations occurred. At the RP2D (400 …

Wearable Surface Electromyography System To Predict Freeze Of Gait In Parkinson's Disease Patients., Anna Moore, Jinxing Li, Christopher H Contag, Luke J Currano, Connor O Pyles, David A Hinkle, Vivek Shinde Patil

Neuroscience Articles

Freezing of gait (FOG) is a disabling yet poorly understood paroxysmal gait disorder affecting the vast majority of patients with Parkinson's disease (PD) as they reach advanced stages of the disorder. Falling is one of the most disabling consequences of a FOG episode; it often results in injury and a future fear of falling, leading to diminished social engagement, a reduction in general fitness, loss of independence, and degradation of overall quality of life. Currently, there is no robust or reliable treatment against FOG in PD. In the absence of reliable and effective treatment for Parkinson's disease, alleviating the consequences …

Factors Associated With Receipt Of Tobacco Treatment Integrated With Nurse Navigation In A Centralized Lung Cancer Screening Program At An Urban Academic Medical Center, Christine S. Shusted, Sarah Mukhtar, James Lee, Brooke Ruane, Emily Muse, Lawrence Emeigh-Mcbride, Eboni Gatson-Anderson, Gregory C. Kane, Kuang-Yi Wen, Hee-Soon Juon, Julie A. Barta

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

PURPOSE: Optimal approaches for tobacco treatment counseling among individuals who currently smoke and are undergoing shared decision-making (SDM) and lung cancer screening (LCS) are unknown. The objective of this cross-sectional study was to determine the rate of reported interest in tobacco treatment counseling and pharmacotherapy among individuals who currently smoke and are receiving integrated nurse navigation for LCS and tobacco treatment in a centralized LCS Program.

METHODS: We identified individuals undergoing SDM through our centralized LCS Program between March 2021 and March 2022. The LCS Program tobacco treatment protocol includes counseling both in-person and via telephone during SDM, LCS results …

Automated Segmentation Of Mri White Matter Hyperintensities In 8421 Patients With Acute Ischemic Stroke, Hosung Kim, Wi-Sun Ryu, Dawid Schellingerhout, Jonghyeok Park, Jinyong Chung, Sang-Wuk Jeong, Dong-Seok Gwak, Beom Joon Kim, Joon-Tae Kim, Keun-Sik Hong, Kyung Bok Lee, Tai Hwan Park, Jong-Moo Park, Kyusik Kang, Yong-Jin Cho, Byung-Chul Lee, Kyung-Ho Yu, Mi Sun Oh, Soo Joo Lee, Jae-Kwan Cha, Dae-Hyun Kim, Jun Lee, Man Seok Park, Hee-Joon Bae, Dong-Eog Kim

Faculty, Staff and Student Publications

Background and purpose: To date, only a few small studies have attempted deep learning-based automatic segmentation of white matter hyperintensity (WMH) lesions in patients with cerebral infarction; this issue is complicated because stroke-related lesions can obscure WMH borders. We developed and validated deep learning algorithms to segment WMH lesions accurately in patients with cerebral infarction using multisite data sets involving 8421 patients with acute ischemic stroke.

Materials and methods: We included 8421 patients with stroke from 9 centers in Korea. 2D UNet and squeeze-and-excitation (SE)-UNet models were trained using 2408 FLAIR MRIs from 3 hospitals and validated using 6013 FLAIR …

Domain-Specific Representation Of Social Inference By Neurons In The Human Amygdala And Hippocampus, Runnan Cao, Julien Dubois, Adam N Mamelak, Ralph Adolphs, Shuo Wang, Ueli Rutishauser

2020-Current year OA Pubs

Inferring the intentions and emotions of others from behavior is crucial for social cognition. While neuroimaging studies have identified brain regions involved in social inference, it remains unknown whether performing social inference is an abstract computation that generalizes across different stimulus categories or is specific to certain stimulus domain. We recorded single-neuron activity from the medial temporal lobe (MTL) and the medial frontal cortex (MFC) in neurosurgical patients performing different types of inferences from images of faces, hands, and natural scenes. Our findings indicate distinct neuron populations in both regions encoding inference type for social (faces, hands) and nonsocial (scenes) …

Clonal Landscape And Clinical Outcomes Of Telomere Biology Disorders: Somatic Rescue And Cancer Mutations, Fernanda Gutierrez-Rodrigues, Emma M Groarke, Natthakan Thongon, Juan Jose Rodriguez-Sevilla, Luiz Fernando B Catto, Marena R Niewisch, Ruba Shalhoub, Lisa J Mcreynolds, Diego V Clé, Bhavisha A Patel, Xiaoyang Ma, Dalton Hironaka, Flávia S Donaires, Nina Spitofsky, Barbara A Santana, Tsung-Po Lai, Lemlem Alemu, Sachiko Kajigaya, Ivana Darden, Weiyin Zhou, Paul V Browne, Subrata Paul, Justin Lack, David J Young, Courtney D Dinardo, Abraham Aviv, Feiyang Ma, Michel Michels De Oliveira, Ana Paula De Azambuja, Cynthia E Dunbar, Malgorzata Olszewska, Emmanuel Olivier, Eirini P Papapetrou, Neelam Giri, Blanche P Alter, Carmem Bonfim, Colin O Wu, Guillermo Garcia-Manero, Sharon A Savage, Neal S Young, Simona Colla, Rodrigo T Calado

Faculty, Staff and Student Publications

Telomere biology disorders (TBDs), caused by pathogenic germ line variants in telomere-related genes, present with multiorgan disease and a predisposition to cancer. Clonal hematopoiesis (CH) as a marker of cancer development and survival in TBDs is poorly understood. Here, we characterized the clonal landscape of a large cohort of 207 patients with TBD with a broad range of age and phenotype. CH occurred predominantly in symptomatic patients and in signature genes typically associated with cancers: PPM1D, POT1, TERT promoter (TERTp), U2AF1S34, and/or TP53. Chromosome 1q gain (Chr1q+) was the commonest karyotypic abnormality. Clinically, multiorgan involvement and CH in TERTp, TP53, …

Integrative Multi-Omics Analysis Uncovers Tumor-Immune-Gut Axis Influencing Immunotherapy Outcomes In Ovarian Cancer, Spencer R Rosario, Mark D Long, Shanmuga Chilakapati, Eduardo Cortes Gomez, Sebastiano Battaglia, Prashant K Singh, Jianmin Wang, Katy Wang, Kristopher Attwood, Suzanne M Hess, A J Robert Mcgray, Kunle Odunsi, Brahm H Segal, Gyorgy Paragh, Song Liu, Jennifer A Wargo, Emese Zsiros

Faculty, Staff and Student Publications

Recurrent ovarian cancer patients, especially those resistant to platinum, lack effective curative treatments. To address this, we conducted a phase 2 clinical trial (NCT02853318) combining pembrolizumab with bevacizumab, to increase T cell infiltration into the tumor, and oral cyclophosphamide, to reduce the number of regulatory T cells. The trial accrued 40 heavily pretreated recurrent ovarian cancer patients. The primary endpoint, progression free survival, was extended to a median of 10.2 months. The secondary endpoints demonstrated an objective response rate of 47.5%, and disease control in 30% of patients for over a year while maintaining a good quality of life. We …