Medicine and Health Sciences Commons^™

Abatacept, Cenicriviroc, Or Infliximab For Treatment Of Adults Hospitalized With Covid-19 Pneumonia: A Randomized Clinical Trial, Jane A O'Halloran, Emily R Ko, Kevin J Anstrom, Eyal Kedar, Matthew W Mccarthy, Reynold A Panettieri, Martin Maillo, Patricia Segura Nunez, Anne M Lachiewicz, Cynthia Gonzalez, P Brian Smith, Sabina Mendivil-Tuchia De Tai, Akram Khan, Alfredo J Mena Lora, Matthias Salathe, Gerardo Capo, Daniel Rodríguez Gonzalez, Thomas F Patterson, Christopher Palma, Horacio Ariza, Maria Patelli Lima, John Blamoun, Esteban C Nannini, Eduardo Sprinz, Analia Mykietiuk, Radica Alicic, Adriana M Rauseo, Cameron R Wolfe, Britta Witting, Jennifer P Wang, Luis Parra-Rodriguez, Tatyana Der, Kate Willsey, Jun Wen, Adam Silverstein, Sean M O'Brien, Hussein R Al-Khalidi, Michael A Maldonado, Richard Melsheimer, William G Ferguson, Steven E Mcnulty, Pearl Zakroysky, Susan Halabi, Daniel K Benjamin, Sandra Butler, Jane C Atkinson, Stacey J Adam, Soju Chang, Lisa Lavange, Michael Proschan, Samuel A Bozzette, William G Powderly, Activ-1 Im Study Group Members

Faculty, Staff and Student Publications

IMPORTANCE: Immune dysregulation contributes to poorer outcomes in COVID-19.

OBJECTIVE: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia.

DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and …

Proteomics Analysis Of Plasma From Middle-Aged Adults Identifies Protein Markers Of Dementia Risk In Later Life, Keenan A Walker, Jingsha Chen, Liu Shi, Yunju Yang, Myriam Fornage, Linda Zhou, Pascal Schlosser, Aditya Surapaneni, Morgan E Grams, Michael R Duggan, Zhongsheng Peng, Gabriela T Gomez, Adrienne Tin, Ron C Hoogeveen, Kevin J Sullivan, Peter Ganz, Joni V Lindbohm, Mika Kivimaki, Alejo J Nevado-Holgado, Noel Buckley, Rebecca F Gottesman, Thomas H Mosley, Eric Boerwinkle, Christie M Ballantyne, Josef Coresh

Faculty, Staff and Student Publications

A diverse set of biological processes have been implicated in the pathophysiology of Alzheimer's disease (AD) and related dementias. However, there is limited understanding of the peripheral biological mechanisms relevant in the earliest phases of the disease. Here, we used a large-scale proteomics platform to examine the association of 4877 plasma proteins with 25-year dementia risk in 10,981 middle-aged adults. We found 32 dementia-associated plasma proteins that were involved in proteostasis, immunity, synaptic function, and extracellular matrix organization. We then replicated the association between 15 of these proteins and clinically relevant neurocognitive outcomes in two independent cohorts. We demonstrated that …

Efficacy And Safety Of Elamipretide In Individuals With Primary Mitochondrial Myopathy: The Mmpower-3 Randomized Clinical Trial, Amel Karaa, Enrico Bertini, Valerio Carelli, Bruce H Cohen, Gregory M Enns, Marni J Falk, Amy Goldstein, Gráinne Siobhan Gorman, Richard Haas, Michio Hirano, Thomas Klopstock, Mary Kay Koenig, Cornelia Kornblum, Costanza Lamperti, Anna Lehman, Nicola Longo, Maria Judit Molnar, Sumit Parikh, Han Phan, Robert D S Pitceathly, Russell Saneto, Fernando Scaglia, Serenella Servidei, Mark Tarnopolsky, Antonio Toscano, Johan L K Van Hove, John Vissing, Jerry Vockley, Jeffrey S Finman, David A Brown, James A Shiffer, Michelango Mancuso, Mmpower-3 Trial Investigators

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Primary mitochondrial myopathies (PMMs) encompass a group of genetic disorders that impair mitochondrial oxidative phosphorylation, adversely affecting physical function, exercise capacity, and quality of life (QoL). Current PMM standards of care address symptoms, with limited clinical impact, constituting a significant therapeutic unmet need. We present data from MMPOWER-3, a pivotal, phase-3, randomized, double-blind, placebo-controlled clinical trial that evaluated the efficacy and safety of elamipretide in participants with genetically confirmed PMM.

METHODS: After screening, eligible participants were randomized 1:1 to receive either 24 weeks of elamipretide at a dose of 40 mg/d or placebo subcutaneously. Primary efficacy endpoints …

Comparison Of Left Bundle Branch Area Pacing And Biventricular Pacing In Candidates For Resynchronization Therapy, Pugazhendhi Vijayaraman, Parikshit S Sharma, Óscar Cano, Shunmuga Sundaram Ponnusamy, Bengt Herweg, Francesco Zanon, Marek Jastrzebski, Jiangang Zou, Mihail G Chelu, Kevin Vernooy, Zachary I Whinnett, Girish M Nair, Manuel Molina-Lerma, Karol Curila, Dipen Zalavadia, Abdul Haseeb, Cicely Dye, Sharath C Vipparthy, Ryan Brunetti, Pawel Moskal, Alexandra Ross, Antonius Van Stipdonk, Jerin George, Yusuf K Qadeer, Mishal Mumtaz, Jeffrey Kolominsky, Syeda A Zahra, Mehrdad Golian, Lina Marcantoni, Faiz A Subzposh, Kenneth A Ellenbogen

Faculty, Staff and Students Publications

Background: Cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) is a well established therapy in patients with reduced left ventricular ejection fraction (LVEF), heart failure, and wide QRS or expected frequent ventricular pacing. Left bundle branch area pacing (LBBAP) has recently been shown to be a safe alternative to BVP.

Objectives: The aim of this study was to compare the clinical outcomes between BVP and LBBAP among patients undergoing CRT.

Methods: This observational study included patients with LVEF ≤35% who underwent BVP or LBBAP for the first time for Class I or II indications for CRT from January 2018 to …

Temporal Trends And Geographic Variations In Mortality Rates From Tobacco And Firearms In The United States, Sarah A Palumbo, Robert S Levine, Janet D Robishaw, Charles H Hennekens

Faculty, Staff and Students Publications

We explored temporal trends and geographic variations in United States of America (US) mortality rates from smoking and firearms from 1999 to 2019. To do so, we used the publicly available Centers for Disease Control and Prevention (CDC) Wide Ranging Online Data for Epidemiologic Research (WONDER) with Multiple Cause of Death files from 1999 to 2019. Using age-specific rates and ArcGIS Pro Advanced software for Optimized Hot Spot Analyses from Esri, we generated maps of statistically significant spatial clusters with 90-99% confidence intervals with the Getis-Ord Gi* statistic for mortality from smoking-related causes and firearms. These data show temporal trends …

Long-Term Outcomes In Patients With Chronic Lymphocytic Leukemia Treated With Ibrutinib: Focus On Hypertension And Cardiovascular Toxicity, Max J Gordon, Jade E Jones, Binsah George, Christine Peterson, Jan A Burger, Nitin Jain, Michael Keating, William G Wierda, Jean-Bernard Durand, Alessandra Ferrajoli

Faculty, Staff and Student Publications

BACKGROUND: Continuous ibrutinib administration is needed to maintain efficacy in patients with chronic lymphocytic leukemia (CLL) and, as such, long-term toxicity is a concern. The authors report the 5-year follow-up of patients with CLL who received treatment with ibrutinib with a focus on hypertension and cardiovascular toxicities.

METHODS: Patient characteristics were assessed, including blood pressure, cardiovascular disease, disease progression, and death. Univariate logistic regression analysis assessed the relation of patient characteristics and the development of new or worsened hypertension. The incidence of hypertensive outcomes was evaluated using competing risk. Survival was estimated using the Kaplan-Meier method.

RESULTS: Three hundred patients …

Effectiveness Of Individualized Counseling On The Duration Of Exclusive Breastfeeding: Study Protocol For A Multicenter, Randomized, Parallel, And Open Clinical Trial., Mariana Torreglosa Ruiz, Elisa Da Conceição Rodrigues, Karine Emanuelle Peixoto Oliveira Da Silva, Cynthya Viana De Resende, Michele Curcino Cavalcanti, Luciano Marques Dos Santos, Monika Wernet, Ana Letícia Monteiro Gomes, Marialda Moreira Christoffel, Maria Beatriz Guimarães Raponi, Jéssica Aparecida Da Silva, Jacqueline Faria De Oliveira, Divanice Contim, Ana Linares

Nursing Faculty Publications

BACKGROUND: Despite the benefits of breastfeeding, early weaning is a reality, so less than 50% of children worldwide and in Brazil are on exclusive breastfeeding in the sixth month of life. A strategy to counteract this scenario is breastfeeding counseling. This study aims to verify the effectiveness of individualized counseling by nurses trained in breastfeeding counseling, on the duration of exclusive breastfeeding, compared to standard care.

METHODS: Multicenter, randomized, parallel, and open clinical trial, with primiparous women aged over 18 years, hospitalized in rooming-in wards at participating centers and hemodynamically stable, aware, and oriented, who had a single-fetus pregnancy and …

Associations Between Age, Sex, Apoe Genotype, And Regional Vascular Physiology In Typically Aging Adults, Nikou L Damestani, John Jacoby, Shrikanth M Yadav, Allison E Lovely, Aurea Michael, Melissa Terpstra, Marziye Eshghi, Barnaly Rashid, Carlos Cruchaga, David H Salat, Meher R Juttukonda

2020-Current year OA Pubs

Altered blood flow in the human brain is characteristic of typical aging. However, numerous factors contribute to inter-individual variation in patterns of blood flow throughout the lifespan. To better understand the mechanisms behind such variation, we studied how sex and APOE genotype, a primary genetic risk factor for Alzheimer's disease (AD), influence associations between age and brain perfusion measures. We conducted a cross-sectional study of 562 participants from the Human Connectome Project - Aging (36 to >90 years of age). We found widespread associations between age and vascular parameters, where increasing age was associated with regional decreases in cerebral blood …

Relative Burden Of Cancer And Noncancer Mortality Among Long-Term Survivors Of Breast, Prostate, And Colorectal Cancer In The Us, Madhav Kc, Jane Fan, Terry Hyslop, Sirad Hassan, Michael Cecchini, Shi-Yi Wang, Andrea Silber, Michael S. Leapman, Ira Leeds, Stephanie B. Wheeler, Lisa P. Spees, Cary P. Gross, Maryam Lustberg, Rachel A. Greenup, Amy C. Justice, Kevin C. Oeffinger, Michaela A. Dinan

Kimmel Cancer Center Faculty Papers

IMPORTANCE: Improvements in cancer outcomes have led to a need to better understand long-term oncologic and nononcologic outcomes and quantify cancer-specific vs noncancer-specific mortality risks among long-term survivors.

OBJECTIVE: To assess absolute and relative cancer-specific vs noncancer-specific mortality rates among long-term survivors of cancer, as well as associated risk factors.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included 627 702 patients in the Surveillance, Epidemiology, and End Results cancer registry with breast, prostate, or colorectal cancer who received a diagnosis between January 1, 2003, and December 31, 2014, who received definitive treatment for localized disease and who were alive 5 …

A Phase 1/2 Study Of Azacitidine, Venetoclax And Pevonedistat In Newly Diagnosed Secondary Aml And In Mds Or Cmmlafter Failure Of Hypomethylating Agents, Nicholas J Short, Muharrem Muftuoglu, Faustine Ong, Lewis Nasr, Walid Macaron, Guillermo Montalban-Bravo, Yesid Alvarado, Mahesh Basyal, Naval Daver, Courtney D Dinardo, Gautam Borthakur, Nitin Jain, Maro Ohanian, Elias Jabbour, Ghayas C Issa, Wei Qiao, Xuelin Huang, Rashmi Kanagal-Shamanna, Keyur P Patel, Prithviraj Bose, Farhad Ravandi, Ricardo Delumpa, Regina Abramova, Guillermo Garcia-Manero, Michael Andreeff, Jorge Cortes, Hagop Kantarjian

Faculty, Staff and Student Publications

BACKGROUND: Pevonedistat is a first-in-class, small molecular inhibitor of NEDD8-activating enzyme that has clinical activity in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Preclinical data suggest synergy of pevonedistat with azacitidine and venetoclax.

METHODS: This single-center, phase 1/2 study evaluated the combination of azacitidine, venetoclax and pevonedistat in older adults with newly diagnosed secondary AML or with MDS or chronic myelomonocytic leukemia (CMML) after failure of hypomethylating agents. Patients received azacitidine 75 mg/m

FINDINGS: Forty patients were enrolled (32 with AML and 8 with MDS/CMML). In the AML cohort, the median age was 74 years (range 61-86 years), and …

A Phase 1/2 Study Of Azacitidine, Venetoclax And Pevonedistat In Newly Diagnosed Secondary Aml And In Mds Or Cmml After Failure Of Hypomethylating Agents, Nicholas J Short, Muharrem Muftuoglu, Faustine Ong, Lewis Nasr, Walid Macaron, Guillermo Montalban-Bravo, Yesid Alvarado, Mahesh Basyal, Naval Daver, Courtney D Dinardo, Gautam Borthakur, Nitin Jain, Maro Ohanian, Elias Jabbour, Ghayas C Issa, Wei Qiao, Xuelin Huang, Rashmi Kanagal-Shamanna, Keyur P Patel, Prithviraj Bose, Farhad Ravandi, Ricardo Delumpa, Regina Abramova, Guillermo Garcia-Manero, Michael Andreeff, Jorge Cortes, Hagop Kantarjian

Faculty, Staff and Student Publications

BACKGROUND: Pevonedistat is a first-in-class, small molecular inhibitor of NEDD8-activating enzyme that has clinical activity in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Preclinical data suggest synergy of pevonedistat with azacitidine and venetoclax.

METHODS: This single-center, phase 1/2 study evaluated the combination of azacitidine, venetoclax and pevonedistat in older adults with newly diagnosed secondary AML or with MDS or chronic myelomonocytic leukemia (CMML) after failure of hypomethylating agents. Patients received azacitidine 75 mg/m

FINDINGS: Forty patients were enrolled (32 with AML and 8 with MDS/CMML). In the AML cohort, the median age was 74 years (range 61-86 years), and …

Mitophagy Promotes Resistance To Bh3 Mimetics In Acute Myeloid Leukemia, Christina Glytsou, Xufeng Chen, Emmanouil Zacharioudakis, Wafa Al-Santli, Hua Zhou, Bettina Nadorp, Soobeom Lee, Audrey Lasry, Zhengxi Sun, Dimitrios Papaioannou, Michael Cammer, Kun Wang, Tomasz Zal, Malgorzata Anna Zal, Bing Z Carter, Jo Ishizawa, Raoul Tibes, Aristotelis Tsirigos, Michael Andreeff, Evripidis Gavathiotis, Iannis Aifantis

Faculty, Staff and Student Publications

BH3 mimetics are used as an efficient strategy to induce cell death in several blood malignancies, including acute myeloid leukemia (AML). Venetoclax, a potent BCL-2 antagonist, is used clinically in combination with hypomethylating agents for the treatment of AML. Moreover, MCL1 or dual BCL-2/BCL-xL antagonists are under investigation. Yet, resistance to single or combinatorial BH3-mimetic therapies eventually ensues. Integration of multiple genome-wide CRISPR/Cas9 screens revealed that loss of mitophagy modulators sensitizes AML cells to various BH3 mimetics targeting different BCL-2 family members. One such regulator is MFN2, whose protein levels positively correlate with drug resistance in patients with AML. MFN2 …

Tissue Mass Spectrometry: How Solid Is Our Future?, Daisy Unsihuay, William S Phipps, Amanda G Paulovich, Jessica R Chapman, Axel Ducret, Livia S Eberlin, Jeffrey M Spraggins, Richard J A Goodwin

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

Comparison Of Patient Exit Interviews With Unannounced Standardised Patients For Assessing Hiv Service Delivery In Zambia: A Study Nested Within A Cluster Randomised Trial, Kombatende Sikombe, Aaloke Mody, Ingrid Eshun-Wilson, Elvin Geng, Et Al.

2020-Current year OA Pubs

OBJECTIVES: To compare unannounced standardised patient approach (eg, mystery clients) with typical exit interviews for assessing patient experiences in HIV care (eg, unfriendly providers, long waiting times). We hypothesise standardised patients would report more negative experiences than typical exit interviews affected by social desirability bias.

SETTING: Cross-sectional surveys in 16 government-operated HIV primary care clinics in Lusaka, Zambia providing antiretroviral therapy (ART).

PARTICIPANTS: 3526 participants aged ≥18 years receiving ART participated in the exit surveys between August 2019 and November 2021.

INTERVENTION: Systematic sample (every n

OUTCOME MEASURES: We compared patient experience among patients who received brief training prior to …

Association Of Circulating Tumor Dna Testing Before Tissue Diagnosis With Time To Treatment Among Patients With Suspected Advanced Lung Cancer: The Accelerate Nonrandomized Clinical Trial, Miguel García-Pardo, Kasia Czarnecka-Kujawa, Jennifer H Law, Alexandra M Salvarrey, Roxanne Fernandes, Zhen J Fan, Thomas K Waddell, Kazuhiro Yasufuku, Geoffrey Liu, Laura L Donahoe, Andrew Pierre, Lisa W Le, Tharsiga Gunasegaran, Noor Ghumman, Frances A Shepherd, Penelope A Bradbury, Adrian G Sacher, Sabine Schmid, Lucy Corke, Jamie Feng, Tracy Stockley, Prodipto Pal, Patrik Rogalla, Christodoulos Pipinikas, Karen Howarth, Bana Ambasager, Laura Mezquita, Ming S Tsao, Natasha B Leighl

Faculty, Staff and Student Publications

IMPORTANCE: Liquid biopsy has emerged as a complement to tumor tissue profiling for advanced non-small cell lung cancer (NSCLC). The optimal way to integrate liquid biopsy into the diagnostic algorithm for patients with newly diagnosed advanced NSCLC remains unclear.

OBJECTIVE: To evaluate the use of circulating tumor DNA (ctDNA) genotyping before tissue diagnosis among patients with suspected advanced NSCLC and its association with time to treatment.

DESIGN, SETTING, AND PARTICIPANTS: This single-group nonrandomized clinical trial was conducted among 150 patients at the Princess Margaret Cancer Centre-University Health Network (Toronto, Ontario, Canada) between July 1, 2021, and November 30, 2022. Patients …

Clinical And Demographic Factors Associated With Covid-19, Severe Covid-19, And Sars-Cov-2 Infection In Adults: A Secondary Cross-Protocol Analysis Of 4 Randomized Clinical Trials, Deborah A Theodore, Angela R Branche, Lily Zhang, Daniel S Graciaa, Madhu Choudhary, Timothy J Hatlen, Raadhiya Osman, Tara M Babu, Samuel T Robinson, Peter B Gilbert, Dean Follmann, Holly Janes, James G Kublin, Lindsey R Baden, Paul Goepfert, Glenda E Gray, Beatriz Grinsztejn, Karen L Kotloff, Cynthia L Gay, Brett Leav, Jacqueline Miller, Ian Hirsch, Jerald Sadoff, Lisa M Dunkle, Kathleen M Neuzil, Lawrence Corey, Ann R Falsey, Hana M El Sahly, Magdalena E Sobieszczyk, Yunda Huang

Faculty, Staff and Student Publications

IMPORTANCE: Current data identifying COVID-19 risk factors lack standardized outcomes and insufficiently control for confounders.

OBJECTIVE: To identify risk factors associated with COVID-19, severe COVID-19, and SARS-CoV-2 infection.

DESIGN, SETTING, AND PARTICIPANTS: This secondary cross-protocol analysis included 4 multicenter, international, randomized, blinded, placebo-controlled, COVID-19 vaccine efficacy trials with harmonized protocols established by the COVID-19 Prevention Network. Individual-level data from participants randomized to receive placebo within each trial were combined and analyzed. Enrollment began July 2020 and the last data cutoff was in July 2021. Participants included adults in stable health, at risk for SARS-CoV-2, and assigned to the placebo group …

Baseline Features And Reasons For Nonparticipation In The Colonoscopy Versus Fecal Immunochemical Test In Reducing Mortality From Colorectal Cancer (Confirm) Study, A Colorectal Cancer Screening Trial, Douglas J Robertson, Jason A Dominitz, Alexander Beed, Kathy D Boardman, Barbara J Del Curto, Peter D Guarino, Thomas F Imperiale, Andrew Lacasse, Meaghan F Larson, Samir Gupta, David Lieberman, Beata Planeta, Aasma Shaukat, Shanaz Sultan, Stacy B Menees, Sameer D Saini, Philip Schoenfeld, Stephan Goebel, Erik C Von Rosenvinge, Gyorgy Baffy, Ildiko Halasz, Marcos C Pedrosa, Lyn Sue Kahng, Riaz Cassim, Katarina B Greer, Margaret F Kinnard, Divya B Bhatt, Kerry B Dunbar, William V Harford, John A Mengshol, Jed E Olson, Swati G Patel, Fadi Antaki, Deborah A Fisher, Brian A Sullivan, Christopher Lenza, Devang N Prajapati, Helen Wong, Rebecca Beyth, John G Lieb, Joseph Manlolo, Fernando V Ona, Rhonda A Cole, Natalia Khalaf, Charles J Kahi, Divyanshoo Rai Kohli, Tarun Rai, Prateek Sharma, Jiannis Anastasiou, Curt Hagedorn, Ronald S Fernando, Christian S Jackson, M Mazen Jamal, Robert H Lee, Farrukh Merchant, Folasade P May, Joseph R Pisegna, Endashaw Omer, Dipendra Parajuli, Adnan Said, Toan D Nguyen, Claudio Ruben Tombazzi, Paul A Feldman, Leslie Jacob, Rachel N Koppelman, Kyle P Lehenbauer, Deepak S Desai, Mohammad F Madhoun, William M Tierney, Minh Q Ho, Heather J Hockman, Christopher Lopez, Emily Carter Paulson, Martin Tobi, Hugo L Pinillos, Michele Young, Nancy C Ho, Ranjan Mascarenhas, Kirrichai Promrat, Pritesh R Mutha, William M Pandak, Tilak Shah, Mitchell Schubert, Frank S Pancotto, Andrew J Gawron, Amelia E Underwood, Samuel B Ho, Priscilla Magno-Pagatzaurtundua, Doris H Toro, Charles H Beymer, Andrew M Kaz, Jill Elwing, Jeffrey A Gill, Susan F Goldsmith, Michael D Yao, Petr Protiva, Heiko Pohl, Tassos Kyriakides

Faculty, Staff and Student Publications

IMPORTANCE: The Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) randomized clinical trial sought to recruit 50 000 adults into a study comparing colorectal cancer (CRC) mortality outcomes after randomization to either an annual fecal immunochemical test (FIT) or colonoscopy.

OBJECTIVE: To (1) describe study participant characteristics and (2) examine who declined participation because of a preference for colonoscopy or stool testing (ie, fecal occult blood test [FOBT]/FIT) and assess that preference's association with geographic and temporal factors.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study within CONFIRM, which completed enrollment through 46 Department of Veterans Affairs …

Baseline Features And Reasons For Nonparticipation In The Colonoscopy Versus Fecal Immunochemical Test In Reducing Mortality From Colorectal Cancer (Confirm) Study, A Colorectal Cancer Screening Trial, Douglas J Robertson, Jill Elwing, Et Al.

2020-Current year OA Pubs

IMPORTANCE: The Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) randomized clinical trial sought to recruit 50 000 adults into a study comparing colorectal cancer (CRC) mortality outcomes after randomization to either an annual fecal immunochemical test (FIT) or colonoscopy.

OBJECTIVE: To (1) describe study participant characteristics and (2) examine who declined participation because of a preference for colonoscopy or stool testing (ie, fecal occult blood test [FOBT]/FIT) and assess that preference's association with geographic and temporal factors.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study within CONFIRM, which completed enrollment through 46 Department of Veterans Affairs …

Assessment Of Gastroesophageal Reflux Symptoms And Sleep Quality Among Women In The Nurses' Health Study Ii, Jane Ha, Raaj S Mehta, Yin Cao, Tianyi Huang, Kyle Staller, Andrew T Chan

2020-Current year OA Pubs

IMPORTANCE: Limited data exist on the association of gastroesophageal reflux (GER) symptoms with sleep quality.

OBJECTIVE: To prospectively investigate the association between GER symptoms and sleep quality.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study included data from the Nurses' Health Study II of female nurses in the US. Participants self-reported the frequency and duration of GER symptoms beginning June 2005, with updates every 4 years through June 2015. Follow-up was completed June 2019, and data were analyzed from November 15, 2022, to June 4, 2023.

EXPOSURES: Frequency and duration of GER symptoms.

MAIN OUTCOMES AND MEASURES: Poor sleep quality …

Who, Where, When: Colorectal Cancer Disparities By Race And Ethnicity, Subsite, And Stage, Kristin M Primm, Andrea Joyce Malabay, Taylor Curry, Shine Chang

Faculty, Staff and Student Publications

BACKGROUND: There are well-established disparities in colorectal cancer (CRC) outcomes between White and Black patients; however, assessments of CRC disparities for other racial/ethnic groups are limited.

METHODS: The Surveillance, Epidemiology, and End Results database identified patients aged 50-74 years with CRC adenocarcinoma from 2000 to 2019. Trends in age-adjusted incidence rates were computed by stage at diagnosis and subsite across five broad race/ethnic groups (White, Black, Asian/Pacific Islander [API], American Indian/Alaskan Native [AIAN], and Hispanic) and four API subgroups (East Asian, Southeast Asian, South Asian, and Pacific Islander) Multivariable logistic regression evaluated associations between race/ethnicity and diagnosis stage. Multivariable Cox …

Effect Of Longitudinal Variation In Tumor Volume Estimation For Mri-Guided Personalization Of Breast Cancer Neoadjuvant Treatment, Natsuko Onishi, Teffany Joy Bareng, Jessica Gibbs, Wen Li, Elissa R Price, Bonnie N Joe, John Kornak, Laura J Esserman, David C Newitt, Nola M Hylton, I-Spy 2 Investigator Network

Faculty, Staff and Student Publications

Purpose To investigate the impact of longitudinal variation in functional tumor volume (FTV) underestimation and overestimation in predicting pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC). Materials and Methods Women with breast cancer who were enrolled in the prospective I-SPY 2 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis 2) from May 2010 to November 2016 were eligible for this retrospective analysis. Participants underwent four MRI examinations during NAC treatment. FTV was calculated based on automated segmentation. Baseline FTV before treatment (FTV0) and the percentage of FTV change at early treatment and inter-regimen …

A Radiomics Model Based On Synthetic Mri Acquisition For Predicting Neoadjuvant Systemic Treatment Response In Triple-Negative Breast Cancer, Ken-Pin Hwang, Nabil A Elshafeey, Aikaterini Kotrotsou, Huiqin Chen, Jong Bum Son, Medine Boge, Rania M Mohamed, Abeer H Abdelhafez, Beatriz E Adrada, Bikash Panthi, Jia Sun, Benjamin C Musall, Shu Zhang, Rosalind P Candelaria, Jason B White, Elizabeth E Ravenberg, Debu Tripathy, Clinton Yam, Jennifer K Litton, Lei Huo, Alastair M Thompson, Peng Wei, Wei T Yang, Mark D Pagel, Jingfei Ma, Gaiane M Rauch

Faculty, Staff and Student Publications

Purpose

To determine if a radiomics model based on quantitative maps acquired with synthetic MRI (SyMRI) is useful for predicting neoadjuvant systemic therapy (NAST) response in triple-negative breast cancer (TNBC).

Materials and Methods

In this prospective study, 181 women diagnosed with stage I–III TNBC were scanned with a SyMRI sequence at baseline and at midtreatment (after four cycles of NAST), producing T1, T2, and proton density (PD) maps. Histopathologic analysis at surgery was used to determine pathologic complete response (pCR) or non-pCR status. From three-dimensional tumor contours drawn on the three maps, 310 histogram and textural features were extracted, resulting …

Association Of Timing Of Moderate-To-Vigorous Physical Activity With Changes In Glycemic Control Over 4 Years In Adults With Type 2 Diabetes From The Look Ahead Trial, Jingyi Qian, Qian Xiao, Michael P Walkup, Mace Coday, Melissa L Erickson, Jessica Unick, John M Jakicic, Kun Hu, Frank A J L Scheer, Roeland J W Middelbeek, Look Ahead Research Group

Faculty, Staff and Student Publications

OBJECTIVE: We aimed to determine the association of the time-of-day of bout-related moderate-to-vigorous physical activity (bMVPA) with changes in glycemic control across 4 years in adults with overweight/obesity and type 2 diabetes.

RESEARCH DESIGN AND METHODS: Among 2,416 participants (57% women; mean age, 59 years) with 7-day waist-worn accelerometry recording at year 1 or 4, we assigned bMVPA timing groups based on the participants' temporal distribution of bMVPA at year 1 and recategorized them at year 4. The time-varying exposure of bMVPA (≥10-min bout) timing was defined as ≥50% of bMVPA occurring during the same time period (morning, midday, afternoon, …

Functional Assessment Of The Dural Lymphatic Vessels Using Dynamic Contrast Mri In Multiple Sclerosis, Refaat E Gabr, John A Lincoln, Khader M Hasan, Larry A Kramer

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: The discovery of glymphatic function in the human brain has generated interest in waste clearance mechanisms in neurological disorders such as multiple sclerosis (MS). However, noninvasive in vivo functional assessment is currently lacking. This work studies the feasibility of a novel intravenous dynamic contrast MRI method to assess the dural lymphatics, a purported pathway contributing to glymphatic clearance.

METHODS: This prospective study included 20 patients with MS (17 women; age = 46.4 [27, 65] years; disease duration = 13.6 [2.1, 38.0] years, expanded disability status score (EDSS) = 2.0 [0, 6.5]). Patients were scanned on a 3.0T …

Eliminating Breast Surgery For Invasive Cancer With Exceptional Response To Neoadjuvant Systemic Therapy: Prospective Multicenter Clinical Trial Planned Initial Feasibility Endpoint, Helen M Johnson, Vicente Valero, Wei T Yang, Benjamin D Smith, Savitri Krishnamurthy, Yu Shen, Heather Lin, Anthony Lucci, Gaiane M Rauch, Henry M Kuerer

Faculty, Staff and Student Publications

Background: Response to neoadjuvant systemic therapy (NST) for breast cancer enables tailoring of subsequent therapy. Image-guided breast biopsy after NST can accurately predict a pathologic complete response (pCR). The feasibility phase of the clinical trial reported here assesses omission of breast surgery followed by radiotherapy in terms of local recurrence before trial expansion.

Study design: Women with unicentric, cT1-2 N0-1 M0 triple-negative (TNBC) or human epidermal growth factor receptor 2-positive breast cancer (HER2+BC) cancer with < 2 cm residual disease on post-NST imaging were eligible to enroll. If no residual invasive or in situ disease was identified by image-guided, vacuum-assisted core biopsy (VACB), breast surgery was omitted, and radiotherapy delivered. The primary endpoint for the feasibility phase was ipsilateral breast tumor recurrence at 6 months. If any recurrence occurred during the feasibility phase the trial would halt.

Results: Thirteen patients were enrolled from March 2017 to October 2018. The mean age was 60.8 years (range 51 to 75) and most patients were …

Association Of Second-Generation Antiandrogens With Cognitive And Functional Toxic Effects In Randomized Clinical Trials: A Systematic Review And Meta-Analysis, Malgorzata K Nowakowska, Rachel M Ortega, Mackenzie R Wehner, Kevin T Nead

Faculty, Staff and Student Publications

Importance: The use of second-generation antiandrogens (AAs) in the treatment of prostate cancer is increasing. Retrospective evidence suggests an association between second-generation AAs and adverse cognitive and functional outcomes, but further data from prospective trials are needed.

Objective: To examine whether evidence from randomized clinical trials (RCTs) in prostate cancer supports an association between second-generation AAs and cognitive or functional toxic effects.

Data sources: PubMed, EMBASE, and Scopus (inception to September 12, 2022).

Study selection: Randomized clinical trials of second-generation AAs (abiraterone, apalutamide, darolutamide, or enzalutamide) among individuals with prostate cancer that reported cognitive toxic effects, asthenic toxic effects (eg, …

View-Vlu Observational Study Of The Effect Of Varithena On Wound Healing In The Treatment Of Venous Leg Ulcers., Michael Y Shao, Stuart Harlin, Beverly Chan, Kathylee Santangelo, Eri Fukaya, Julianne Stoughton, Raghu Kolluri

Heart and Vascular Articles

OBJECTIVE: Chronic venous hypertension, triggered by venous reflux and/or obstruction, leads to skin changes and venous leg ulcers (VLUs). Compression therapy is the standard of care, but many wounds remain unhealed. The objectives of this study were to observe the effects of endovenous chemical ablation with commercially available 1% polidocanol injectable microfoam on VLU healing and recurrence rates.

METHODS: The VIEW VLU study was a multicenter, open-label, phase IV registry of patients with active VLUs resulting from venous insufficiency of the great saphenous vein and/or anterior accessory saphenous vein systems who underwent ablation with 1% polidocanol microfoam. Primary outcomes included …

Accuracy Of Artificial Intelligence In Estimating Best-Corrected Visual Acuity From Fundus Photographs In Eyes With Diabetic Macular Edema, William Paul, Philippe Burlina, Rohita Mocharla, Neil Joshi, Zhuolin Li, Sophie Gu, Onnisa Nanegrungsunk, Kira Lin, Susan B Bressler, Cindy X Cai, Jun Kong, T Y Alvin Liu, Hadi Moini, Weiming Du, Fouad Amer, Karen Chu, Robert Vitti, Farshid Sepehrband, Neil M Bressler

Faculty, Staff and Students Publications

IMPORTANCE: Best-corrected visual acuity (BCVA) is a measure used to manage diabetic macular edema (DME), sometimes suggesting development of DME or consideration of initiating, repeating, withholding, or resuming treatment with anti-vascular endothelial growth factor. Using artificial intelligence (AI) to estimate BCVA from fundus images could help clinicians manage DME by reducing the personnel needed for refraction, the time presently required for assessing BCVA, or even the number of office visits if imaged remotely.

OBJECTIVE: To evaluate the potential application of AI techniques for estimating BCVA from fundus photographs with and without ancillary information.

DESIGN, SETTING, AND PARTICIPANTS: Deidentified color fundus …

Systemic Adverse Events Among Patients With Diabetes Treated With Intravitreal Anti-Vascular Endothelial Growth Factor Injections, Sidra Zafar, Annette Walder, Salim Virani, Kristin Biggerstaff, Silvia Orengo-Nania, Jonathan Chang, Roomasa Channa

Faculty, Staff and Students Publications

IMPORTANCE: Anti-vascular endothelial growth factor (VEGF) agents are currently the mainstay of treatment for diabetic retinopathy (DR). Although effective, data on their systemic safety remains inconclusive, particularly in high-risk patient groups.

OBJECTIVE: To explore the systemic safety of intravitreal anti-VEGF agents among patients with diabetes.

DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective, longitudinal population-based analysis of the Corporate Data Warehouse, a large-scale database of patients within the US Veteran Health Affairs. All patients 18 years and older with type 2 diabetes who were seen at any Veterans Affairs health care facility in the US between January 1, 2011, and …

Characterization Of The Oral Microbiota Among Middle-Aged Men With And Without Human Papillomavirus Infection, Kristina R Dahlstrom, Andrew G Sikora, Yanhong Liu, Chia-Chi Chang, Peng Wei, Erich M Sturgis, Guojun Li

Faculty, Staff and Student Publications

OBJECTIVES: To characterize the oral microbiota among middle-aged men and identify differences between men with a prevalent oral high-risk (oncogenic) HPV infection and those without.

MATERIALS AND METHODS: This was a case-control study nested within a prospective screening study for HPV-related cancers among middle-aged men. 16S rRNA sequencing was used to characterize the oral microbiota and the cobas HPV Test was used to detect presence of oral high-risk HPV types. We determined the overall composition of the oral microbiota and assessed differences in relative abundance of bacterial taxa as well as alpha and beta diversity among men with a prevalent …