Digital Commons Network^™

Alliance Foundation Trial 09: A Randomized, Multicenter, Phase 2 Trial Evaluating Two Sequences Of Pembrolizumab And Standard Platinum-Based Chemotherapy In Patients With Metastatic Nsclc, Thomas A Hensing, Xiaofei Wang, Thomas E Stinchcombe, Junheng Gao, Michael V Knopp, Mark Watson, Arkadiusz Z Dudek, Stephen L Graziano, Jyoti D Patel, Bryan A Faller, Konstantin H Dragnev, David Kozono, Everett E Vokes

2020-Current year OA Pubs

INTRODUCTION: The sequence of chemotherapy and pembrolizumab may affect antitumor immune response and efficacy of immunotherapy.

METHODS: This multicenter, randomized, phase 2 trial was designed to evaluate the efficacy of two sequences of chemotherapy and pembrolizumab in patients with stage 4 NSCLC. Both arms were considered investigational, and the study used a "pick a winner" design. The primary end point was objective response rate by independent radiologic review after eight cycles (24 wk). Patients were randomized 1:1 to arm A (chemotherapy for four cycles followed by pembrolizumab for four cycles) or arm B (pembrolizumab for four cycles followed by chemotherapy …

Developmental Differences In Affective Representation Between Prefrontal And Subcortical Structures, William J Mitchell, Lindsey J Tepfer, Nicole M Henninger, Susan B Perlman, Vishnu P Murty, Chelsea Helion

2020-Current year OA Pubs

Developmental studies have identified differences in prefrontal and subcortical affective structures between children and adults, which correspond with observed cognitive and behavioral maturations from relatively simplistic emotional experiences and expressions to more nuanced, complex ones. However, developmental changes in the neural representation of emotions have not yet been well explored. It stands to reason that adults and children may demonstrate observable differences in the representation of affect within key neurological structures implicated in affective cognition. Forty-five participants (25 children; 20 adults) passively viewed positive, negative, and neutral clips from popular films while undergoing functional magnetic resonance imaging (fMRI). Using representational …

Effects Of A Dvd-Delivered Randomized Controlled Physical Activity Intervention On Functional Health In Cancer Survivors, Elizabeth A Salerno, Neha P Gothe, Jason Fanning, Lindsay L Peterson, Graham A Colditz, Edward Mcauley

2020-Current year OA Pubs

BACKGROUND: Supervised physical activity interventions improve functional health during cancer survivorship, but remain costly and inaccessible for many. We previously reported on the benefits of a DVD-delivered physical activity program (FlexToBa™) in older adults. This is a secondary analysis of the intervention effects among cancer survivors in the original sample.

METHODS: Low active, older adults who self-reported a history of cancer (N = 46; M time since diagnosis = 10.7 ± 9.4 years) participated in a 6-month, home-based physical activity intervention. Participants were randomized to either the DVD-delivered physical activity program focused on flexibility, toning, and balance (FlexToBa™; n = …

Altered Neuronal Physiology, Development, And Function Associated With A Common Chromosome 15 Duplication Involving Chrna7, Kesavan Meganathan, Ramachandran Prakasam, Dustin Baldridge, Paul Gontarz, Bo Zhang, Fumihiko Urano, Azad Bonni, Susan E Maloney, Tychele N Turner, James E Huettner, John N Constantino, Kristen L Kroll

2020-Current year OA Pubs

BACKGROUND: Copy number variants (CNVs) linked to genes involved in nervous system development or function are often associated with neuropsychiatric disease. While CNVs involving deletions generally cause severe and highly penetrant patient phenotypes, CNVs leading to duplications tend instead to exhibit widely variable and less penetrant phenotypic expressivity among affected individuals. CNVs located on chromosome 15q13.3 affecting the alpha-7 nicotinic acetylcholine receptor subunit (CHRNA7) gene contribute to multiple neuropsychiatric disorders with highly variable penetrance. However, the basis of such differential penetrance remains uncharacterized. Here, we generated induced pluripotent stem cell (iPSC) models from first-degree relatives with a 15q13.3 duplication and …

Statistical Analysis Of Two Arm Randomized Pre-Post Designs With One Post-Treatment Measurement, Fei Wan

2020-Current year OA Pubs

BACKGROUND: Randomized pre-post designs, with outcomes measured at baseline and after treatment, have been commonly used to compare the clinical effectiveness of two competing treatments. There are vast, but often conflicting, amount of information in current literature about the best analytic methods for pre-post designs. It is challenging for applied researchers to make an informed choice.

METHODS: We discuss six methods commonly used in literature: one way analysis of variance ("ANOVA"), analysis of covariance main effect and interaction models on the post-treatment score ("ANCOVAI" and "ANCOVAII"), ANOVA on the change score between the baseline and post-treatment scores ("ANOVA-Change"), repeated measures …

The Effect Of Virtual Mindfulness-Based Interventions On Sleep Quality: A Systematic Review Of Randomized Controlled Trials, Amanda Jiang, Michael Rosario, Sara Stahl, Jessica M Gill, Heather L Rusch

2020-Current year OA Pubs

PURPOSE OF REVIEW: We summarized peer-reviewed literature investigating the effect of virtual mindfulness-based interventions (MBIs) on sleep quality. We aimed to examine the following three questions: (1) do virtual MBIs improve sleep quality when compared with control groups; (2) does the effect persist long-term; and (3) is the virtual delivery method equally feasible compared to the in-person delivery method?

RECENT FINDINGS: Findings suggest that virtual MBIs are equivalent to evidence-based treatments, and to a limited extent, more effective than non-specific active controls at reducing some aspects of sleep disturbance. Overall, virtual MBIs are more effective at improving sleep quality than …

The Informed Road Map To Prevention Of Alzheimer Disease: A Call To Arms, Eric Mcdade, Jorge J Llibre-Guerra, David M Holtzman, John C Morris, Randall J Bateman

2020-Current year OA Pubs

Alzheimer disease (AD) prevention trials hold the promise to delay or prevent cognitive decline and dementia onset by intervening before significant neuronal damage occurs. In recent years, the first AD prevention trials have launched and are yielding important findings on the biology of targeting asymptomatic AD pathology. However, there are limitations that impact the design of these prevention trials, including the translation of animal models that recapitulate key stages and multiple pathological aspects of the human disease, missing target validation in asymptomatic disease, uncertain causality of the association of pathophysiologic changes with cognitive and clinical symptoms, and limited biomarker validation …

Exploring Perceptions Of Healthcare Technologies Enabled By Artificial Intelligence: An Online, Scenario-Based Survey, Alison L Antes, Sara Burrous, Bryan A Sisk, Matthew J Schuelke, Jason D Keune, James M Dubois

2020-Current year OA Pubs

BACKGROUND: Healthcare is expected to increasingly integrate technologies enabled by artificial intelligence (AI) into patient care. Understanding perceptions of these tools is essential to successful development and adoption. This exploratory study gauged participants' level of openness, concern, and perceived benefit associated with AI-driven healthcare technologies. We also explored socio-demographic, health-related, and psychosocial correlates of these perceptions.

METHODS: We developed a measure depicting six AI-driven technologies that either diagnose, predict, or suggest treatment. We administered the measure via an online survey to adults (N = 936) in the United States using MTurk, a crowdsourcing platform. Participants indicated their level of openness …

A Single Intranasal Or Intramuscular Immunization With Chimpanzee Adenovirus-Vectored Sars-Cov-2 Vaccine Protects Against Pneumonia In Hamsters, Traci L. Bricker, Tamarand L. Darling, Ahmed O. Hassan, Houda H. Harastani, Allison Soung, Xiaoping Jiang, Ya-Nan Dai, Haiyan Zhao, Lucas J. Adams, Michael J. Holtzman, Adam L. Bailey, James Brett Case, Daved H. Fremont, Robyn Klein, Michael S. Diamond, Adrianus C. M. Boon

2020-Current year OA Pubs

The development of an effective vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), is a global priority. Here, we compare the protective capacity of intranasal and intramuscular delivery of a chimpanzee adenovirus-vectored vaccine encoding a prefusion stabilized spike protein (chimpanzee adenovirus [ChAd]-SARS-CoV-2-S) in Golden Syrian hamsters. Although immunization with ChAd-SARS-CoV-2-S induces robust spike-protein-specific antibodies capable of neutralizing the virus, antibody levels in serum are higher in hamsters vaccinated by an intranasal compared to intramuscular route. Accordingly, against challenge with SARS-CoV-2, ChAd-SARS-CoV-2-S-immunized hamsters are protected against less weight loss and have reduced …

The Clinical Sustainability Assessment Tool: Measuring Organizational Capacity To Promote Sustainability In Healthcare, Sara Malone, Kim Prewitt, Rachel Hackett, John C Lin, Virginia Mckay, Callie Walsh-Bailey, Douglas A Luke

2020-Current year OA Pubs

BACKGROUND: Few validated assessment tools are available to increase understanding and measure factors associated with sustainment of clinical practices, an increasingly recognized need among clinicians. We describe the development of the Clinical Sustainability Assessment Tool (CSAT), designed to assess factors that contribute to sustainable practices in clinical settings.

METHODS: Sixty-four participants from clinical and research fields participated in concept mapping and were recruited to brainstorm factors that lead to sustained clinical practices. Once repeated factors were removed, participants sorted items based on similarity and rated them by importance and feasibility. Using concept mapping analyses, items were grouped into meaningful domains …

Significant Regional Differences In Antibiotic Use Across 576 Us Hospitals And 11 701 326 Adult Admissions, 2016-2017, Katherine E Goodman, Sara E Cosgrove, Lisa Pineles, Laurence S Magder, Deverick J Anderson, Elizabeth Dodds Ashley, Ronald E Polk, Hude Quan, William E Trick, Keith F Woeltje, Surbhi Leekha, Anthony D Harris

2020-Current year OA Pubs

BACKGROUND: Quantifying the amount and diversity of antibiotic use in United States hospitals assists antibiotic stewardship efforts but is hampered by limited national surveillance. Our study aimed to address this knowledge gap by examining adult antibiotic use across 576 hospitals and nearly 12 million encounters in 2016-2017.

METHODS: We conducted a retrospective study of patients aged ≥ 18 years discharged from hospitals in the Premier Healthcare Database between 1 January 2016 and 31 December 2017. Using daily antibiotic charge data, we mapped antibiotics to mutually exclusive classes and to spectrum of activity categories. We evaluated relationships between facility and case-mix …

Coding And Noncoding Variants In Ebf3 Are Involved In Hadds And Simplex Autism, Evin M Padhi, Jeffrey K Ng, Elvisa Mehinovic, Tychele N Turner, Et Al.

2020-Current year OA Pubs

BACKGROUND: Previous research in autism and other neurodevelopmental disorders (NDDs) has indicated an important contribution of protein-coding (coding) de novo variants (DNVs) within specific genes. The role of de novo noncoding variation has been observable as a general increase in genetic burden but has yet to be resolved to individual functional elements. In this study, we assessed whole-genome sequencing data in 2671 families with autism (discovery cohort of 516 families, replication cohort of 2155 families). We focused on DNVs in enhancers with characterized in vivo activity in the brain and identified an excess of DNVs in an enhancer named hs737. …

Quality-Adjusted Time Without Symptoms Of Disease Or Toxicity (Q-Twist) Analysis Of Cpx-351 Versus 7 + 3 In Older Adults With Newly Diagnosed High-Risk/Secondary Aml, Jorge E Cortes, Tara L Lin, Geoffrey L Uy, Robert J Ryan, Stefan Faderl, Jeffrey E Lancet

2020-Current year OA Pubs

BACKGROUND: CPX-351 (United States: Vyxeos

METHODS: Patients were randomized 1:1 between December 20, 2012 and November 11, 2014 to receive induction with CPX-351 or 7 + 3. Survival time for each patient was partitioned into 3 health states: TOX (time with any grade 3 or 4 toxicity or prior to remission), TWiST (time in remission without relapse or grade 3 or 4 toxicity), and REL (time after relapse). Within each treatment arm, Q-TWiST was calculated by adding the mean time spent in each health state weighted by its respective quality-of-life, represented by health utility. The relative Q-TWiST gain, calculated as …

Current State Of Scientific Evidence On Internet-Based Interventions For The Treatment Of Depression, Anxiety, Eating Disorders And Substance Abuse: An Overview Of Systematic Reviews And Meta-Analyses, C Barr Taylor, Andrea K Graham, Rachael E Flatt, Karin Waldherr, Ellen E Fitzsimmons-Craft

2020-Current year OA Pubs

BACKGROUND: ICare represents a consortium of European Investigators examining the effects of online mental health care for a variety of common mental health disorders provided in a variety of settings. This article provides an overview of the evidence of effectiveness for Internet-based treatment for four common mental health disorders that are the focus of much of this work: depression, anxiety, substance abuse and eating disorders.

METHODS: The overview focused primarily on systematic reviews and meta-analyses identified through PubMed (Ovid) and other databases and published in English. Given the large number of reviews specific to depression, anxiety, substance abuse and/or eating …

Alkbh3 Partner Ascc3 Mediates P-Body Formation And Selective Clearance Of Mms-Induced 1-Methyladenosine And 3-Methylcytosine From Mrna, Kristian Lied Wollen, Lars Hagen, Cathrine B Vågbø, Renana Rabe, Tobias S Iveland, Per Arne Aas, Animesh Sharma, Bjørnar Sporsheim, Hilde O Erlandsen, Vuk Palibrk, Magnar Bjørås, Davi M Fonseca, Nima Mosammaparast, Geir Slupphaug

2020-Current year OA Pubs

BACKGROUND: Reversible enzymatic methylation of mammalian mRNA is widespread and serves crucial regulatory functions, but little is known to what degree chemical alkylators mediate overlapping modifications and whether cells distinguish aberrant from canonical methylations.

METHODS: Here we use quantitative mass spectrometry to determine the fate of chemically induced methylbases in the mRNA of human cells. Concomitant alteration in the mRNA binding proteome was analyzed by SILAC mass spectrometry.

RESULTS: MMS induced prominent direct mRNA methylations that were chemically identical to endogenous methylbases. Transient loss of 40S ribosomal proteins from isolated mRNA suggests that aberrant methylbases mediate arrested translational initiation and …

Cystic Fibrosis Foundation Consensus Statements For The Care Of Cystic Fibrosis Lung Transplant Recipients, Pali Shah, Marina Litvin, Ramsey R Hachem, Et Al.

2020-Current year OA Pubs

Cystic fibrosis (CF) is the indication for transplantation in approximately 15% of recipients worldwide, and Cystic Fibrosis Lung Transplant Recipients (CFLTRs) have excellent long-term outcomes. Yet, CFLTRs have unique comorbidities that require specialized care. The objective of this document is to provide recommendations to CF and lung transplant clinicians for the management of perioperative and underlying comorbidities of CFLTRs and the impact of transplantation on these comorbidities. The Cystic Fibrosis Foundation (CFF) organized a multidisciplinary committee to develop CF Lung Transplant Clinical Care Recommendations. Three workgroups were formed to develop focused questions. Following a literature search, consensus recommendations were developed …

Excimer Laser Coronary Angioplasty In Coronary Lesions: Use And Safety From The Ncdr/Cath Pci Registry, Marc Sintek, Edward Coverstone, Richard Bach, Alan Zajarias, John Lasala, Howard Kurz, Kevin Kennedy, Jasvindar Singh

2020-Current year OA Pubs

[Figure: see text].

Deteriorated Regional Calf Microcirculation Measured By Contrast-Free Mri In Patients With Diabetes Mellitus And Relation With Physical Activity, Jie Zheng, Christopher Sorensen, Ran Li, Hongyu An, Charles F Hildebolt, Mohamed A Zayed, Michael J Mueller, Mary K Hastings

2020-Current year OA Pubs

OBJECTIVE: To evaluate regional calf muscle microcirculation in people with diabetes mellitus (DM) with and without foot ulcers, compared to healthy control people without DM, using contrast-free magnetic resonance imaging methods.

METHODS: Three groups of subjects were recruited: non-DM controls, DM, and DM with foot ulcers (DM + ulcer), all with ankle brachial index (ABI) > 0.9. Skeletal muscle blood flow (SMBF) and oxygen extraction fraction (SMOEF) in calf muscle were measured at rest and during a 5-min isometric ankle plantarflexion exercise. Subjects completed the Yale physical activity survey.

RESULTS: The exercise SMBF (ml/min/100 g) of the medial gastrocnemius muscle were …

Oral Once-Daily Berotralstat For The Prevention Of Hereditary Angioedema Attacks: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial, Bruce Zuraw, H James Wedner, Et Al.

2020-Current year OA Pubs

BACKGROUND: Berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein in development for the prophylaxis of hereditary angioedema (HAE) attacks.

OBJECTIVE: Our aim was to determine the efficacy, safety, and tolerability of berotralstat in patients with HAE over a 24-week treatment period (the phase 3 APeX-2 trial).

METHODS: APeX-2 was a double-blind, parallel-group study that randomized patients at 40 sites in 11 countries 1:1:1 to receive once-daily berotralstat in a dose of 110 mg or 150 mg or placebo (Clinicaltrials.gov identifier NCT03485911). Patients aged 12 years or older with HAE due to C1 inhibitor deficiency and at least 2 …

The New (Version 9) American Joint Committee On Cancer Tumor, Node, Metastasis Staging For Cervical Cancer, Alexander B Olawaiye, Thomas P Baker, M Kay Washington, David G Mutch

2020-Current year OA Pubs

The American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging for all cancer sites has been periodically updated as a published manual for many years. The last update, the eighth edition AJCC Cancer Staging Manual went into use on January 1, 2018. The AJCC has since restructured and updated its processes, and all AJCC staging-related data are now housed on its new application programming interface. Consequently, the next AJCC TNM staging update, AJCC version 9 TNM staging, will be published electronically and will be released chapter by chapter. The first chapter of version 9 AJCC TNM staging is …

Sonothermogenetics For Noninvasive And Cell-Type Specific Deep Brain Neuromodulation, Yaoheng Yang, Christopher Pham Pacia, Dezhuang Ye, Lifei Zhu, Hongchae Baek, Yimei Yue, Jinyun Yuan, Mark J Miller, Jianmin Cui, Joseph P Culver, Michael R Bruchas, Hong Chen

2020-Current year OA Pubs

BACKGROUND: Critical advances in the investigation of brain functions and treatment of brain disorders are hindered by our inability to selectively target neurons in a noninvasive manner in the deep brain.

OBJECTIVE: This study aimed to develop sonothermogenetics for noninvasive, deep-penetrating, and cell-type-specific neuromodulation by combining a thermosensitive ion channel TRPV1 with focused ultrasound (FUS)-induced brief, non-noxious thermal effect.

METHODS: The sensitivity of TRPV1 to FUS sonication was evaluated in vitro. It was followed by in vivo assessment of sonothermogenetics in the activation of genetically defined neurons in the mouse brain by two-photon calcium imaging. Behavioral response evoked by sonothermogenetic …

Results From 2 Cohort Studies In Central Africa Show That Clearance Of Wuchereria Bancrofti Infection After Repeated Rounds Of Mass Drug Administration With Albendazole Alone Is Closely Linked To Individual Adherence, Jérémy T Campillo, Naomi P Awaca-Uvon, Francois Missamou, Jean-Paul Tambwe, Godefroy Kuyangisa-Simuna, Gary J Weil, Frédéric Louya, Michel Boussinesq, Sébastien D S Pion, Cédric B Chesnais

2020-Current year OA Pubs

BACKGROUND: Two community trials conducted from 2012 to 2018 in the Republic of Congo and the Democratic Republic of the Congo demonstrated the efficacy of semiannual mass drug administration (MDA) with albendazole (ALB) alone on lymphatic filariasis (LF). However, a high interindividual heterogeneity in the clearance of infection was observed.

METHODS: We analyzed trial data to assess the effect of individual adherence to ALB MDA on clearance of circulating filarial antigenemia (CFA) and microfilaremia. Community residents were offered a single dose of ALB every 6 months and tested for LF with a rapid test for CFA at baseline and then …

Mechanisms Underlying Disorders Of Consciousness: Bridging Gaps To Move Toward An Integrated Translational Science, Andrea I Luppi, Joshua Cain, Lennart R B Spindler, Urszula J Górska, Daniel Toker, Andrew E Hudson, Emery N Brown, Michael N Diringer, Robert D Stevens, Marcello Massimini, Martin M Monti, Emmanuel A Stamatakis, Melanie Boly, Curing Coma Campaign And Its Contributing Collaborators

2020-Current year OA Pubs

AIM: In order to successfully detect, classify, prognosticate, and develop targeted therapies for patients with disorders of consciousness (DOC), it is crucial to improve our mechanistic understanding of how severe brain injuries result in these disorders.

METHODS: To address this need, the Curing Coma Campaign convened a Mechanisms Sub-Group of the Coma Science Work Group (CSWG), aiming to identify the most pressing knowledge gaps and the most promising approaches to bridge them.

RESULTS: We identified a key conceptual gap in the need to differentiate the neural mechanisms of consciousness per se, from those underpinning connectedness to the environment and behavioral …

Outcomes For Continuous Subcutaneous Insulin Infusion Users In Young Adults From Lower Socioeconomic Backgrounds, Alexis M Mckee, Stewart G Albert, Noor Al-Hammadi, Leslie J Hinyard

2020-Current year OA Pubs

OBJECTIVE: Diabetes technology is available and its efficacy and safety have been demonstrated; however, there is little evidence as to how this technology is being utilized and its effectiveness in vulnerable populations. This study evaluated differences in outcomes for young adults in the United States (U.S.) from lower socioeconomic (SES) backgrounds with type 1 diabetes (T1D) managed on continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI) or fixed-dose insulin (FDI).

RESEARCH DESIGN METHODS AND PARTICIPANTS: Utilizing the Optum® de-identified Electronic Health Record data set between 2008 and 2018 to perform a retrospective, cohort study, we identified 805 subjects …

Enabling Qualitative Research Data Sharing Using A Natural Language Processing Pipeline For Deidentification: Moving Beyond Hipaa Safe Harbor Identifiers, Aditi Gupta, Albert Lai, Jessica Mozersky, Xiaoteng Ma, Heidi Walsh, James M Dubois

2020-Current year OA Pubs

OBJECTIVE: Sharing health research data is essential for accelerating the translation of research into actionable knowledge that can impact health care services and outcomes. Qualitative health research data are rarely shared due to the challenge of deidentifying text and the potential risks of participant reidentification. Here, we establish and evaluate a framework for deidentifying qualitative research data using automated computational techniques including removal of identifiers that are not considered HIPAA Safe Harbor (HSH) identifiers but are likely to be found in unstructured qualitative data.

MATERIALS AND METHODS: We developed and validated a pipeline for deidentifying qualitative research data using automated …

Characteristics Of U.S. Acute Care Hospitals That Have Implemented Telemedicine Critical Care, Uchenna R. Ofoma, Thomas M. Maddox, Chamila Perera, R. J. Waken, Anne M. Drewry, Lei Liu, Walter Boyle, Marin Kollef, Karen E. Joynt Maddox

2020-Current year OA Pubs

OBJECTIVES: Telemedicine critical care is associated with improved efficiency, quality, and cost-effectiveness. As of 2010, fewer than 5% of U.S. hospitals had telemedicine critical care, and fewer than 10% of ICU beds were covered. We evaluated recent telemedicine critical care implementation and bed coverage rates in the United States and compared characteristics of hospitals with and without telemedicine critical care.

DESIGN: Cross-sectional study of 2018 American Hospital Association Annual Survey Database.

SETTING: U.S. hospitals.

PATIENTS: None.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: We obtained data regarding telemedicine critical care implementation, ICU capability (defined as ≥ 1 ICU bed), other hospital …

Epigenetic Regulation During Human Cortical Development: Seq-Ing Answers From The Brain To The Organoid, Emily M A Lewis, Komal Kaushik, Luke A Sandoval, Irene Antony, Sabine Dietmann, Kristen L Kroll

2020-Current year OA Pubs

Epigenetic regulation plays an important role in controlling gene expression during complex processes, such as development of the human brain. Mutations in genes encoding chromatin modifying proteins and in the non-protein coding sequences of the genome can potentially alter transcription factor binding or chromatin accessibility. Such mutations can frequently cause neurodevelopmental disorders, therefore understanding how epigenetic regulation shapes brain development is of particular interest. While epigenetic regulation of neural development has been extensively studied in murine models, significant species-specific differences in both the genome sequence and in brain development necessitate human models. However, access to human fetal material is limited …

Bintrafusp Alfa, A Bifunctional Fusion Protein Targeting Tgf-Β And Pd-L1, In Patients With Esophageal Adenocarcinoma: Results From A Phase 1 Cohort, Benjamin Tan, Adnan Khattak, Enriqueta Felip, Karen Kelly, Patricia Rich, Ding Wang, Christoph Helwig, Isabelle Dussault, Laureen S Ojalvo, Nicolas Isambert

2020-Current year OA Pubs

BACKGROUND: Esophageal adenocarcinoma patients have limited treatment options. TGF-β can be upregulated in esophageal adenocarcinoma, and blocking this pathway may enhance clinical response to PD-(L)1 inhibitors. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β "trap") fused to a human IgG1 mAb blocking PD-L1.

OBJECTIVE: The objective of this study was to investigate the efficacy and safety of bintrafusp alfa in patients with advanced, post-platinum esophageal adenocarcinoma, unselected for PD-L1 expression.

PATIENTS AND METHODS: In this phase 1 study, patients with post-platinum, PD-L1-unselected esophageal adenocarcinoma received bintrafusp alfa 1200 mg …

Active Surveillance Of Metastatic Renal Cell Carcinoma: Results From A Prospective Observational Study (Marcc), Michael R Harrison, Russell K Pachynski, Et Al.

2020-Current year OA Pubs

BACKGROUND: Systemic therapy (ST) can be deferred in patients who have metastatic renal cell carcinoma (mRCC) and slow-growing metastases. Currently, this subset of patients managed with active surveillance (AS) is not well described in the literature.

METHODS: This was a prospective observational study of patients with mRCC across 46 US community and academic centers. The objective was to describe baseline characteristics and demographics of patients with mRCC initially managed by AS, reasons for AS, and patient outcomes. Descriptive statistics were used to characterize demographics, baseline characteristics, and patient-related outcomes. Wilcoxon 2-sample rank-sum tests and χ

RESULTS: Of 504 patients, mRCC …

Implementing An Electronic Clinical Decision Support Tool Into Routine Care: A Qualitative Study Of Stakeholders' Perceptions Of A Post-Mastectomy Breast Reconstruction Tool, Jessica Boateng, Clara N Lee, Randi E Foraker, Terence M Myckatyn, Kimi Spilo, Courtney Goodwin, Mary C Politi

2020-Current year OA Pubs

No abstract provided.