Medicine and Health Sciences Commons^™

Comparison Of Standard And Penalized Logistic Regression In Risk Model Development, Yan Yan, Zhizhou Yang, Tara R Semenkovich, Benjamin D Kozower, Bryan F Meyers, Ruben G Nava, Daniel Kreisel, Varun Puri

2020-Current year OA Pubs

OBJECTIVE: Regression models are ubiquitous in thoracic surgical research. We aimed to compare the value of standard logistic regression with the more complex but increasingly used penalized regression models using a recently published risk model as an example.

METHODS: Using a standardized data set of clinical T1-3N0 esophageal cancer patients, we created models to predict the likelihood of unexpected pathologic nodal disease after surgical resection. Models were fitted using standard logistic regression or penalized regression (ridge, lasso, elastic net, and adaptive lasso). We compared the model performance (Brier score, calibration slope, C statistic, and overfitting) of standard regression with penalized …

The Echelon-2 Trial: 5-Year Results Of A Randomized, Phase Iii Study Of Brentuximab Vedotin With Chemotherapy For Cd30-Positive Peripheral T-Cell Lymphoma, S Horwitz, N L Bartlett, Et Al.

2020-Current year OA Pubs

BACKGROUND: For patients with peripheral T-cell lymphoma (PTCL), outcomes using frontline treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapy are typically poor. The ECHELON-2 study demonstrated that brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) exhibited statistically superior progression-free survival (PFS) per independent central review and improvements in overall survival versus CHOP for the frontline treatment of patients with systemic anaplastic large cell lymphoma or other CD30-positive PTCL.

PATIENTS AND METHODS: ECHELON-2 is a double-blind, double-dummy, randomized, placebo-controlled, active-comparator phase III study. We present an exploratory update of the ECHELON-2 study, including an analysis of 5-year PFS …

Numbers And Narratives: How Qualitative Methods Can Strengthen The Science Of Paediatric Antimicrobial Stewardship, Charlotte Z Woods-Hill, Anping Xie, John Lin, Heather A Wolfe, Alex S Plattner, Sara Malone, Kathleen Chiotos, Julia E Szymczak

2020-Current year OA Pubs

Antimicrobial and diagnostic stewardship initiatives have become increasingly important in paediatric settings. The value of qualitative approaches to conduct stewardship work in paediatric patients is being increasingly recognized. This article seeks to provide an introduction to basic elements of qualitative study designs and provide an overview of how these methods have successfully been applied to both antimicrobial and diagnostic stewardship work in paediatric patients. A multidisciplinary team of experts in paediatric infectious diseases, paediatric critical care and qualitative methods has written a perspective piece introducing readers to qualitative stewardship work in children, intended as an overview to highlight the importance …

Prevalence Of Surgical Procedures At Symptomatic Onset Of Prion Disease, Amanda L Porter, Christian C Prusinski, Evelyn Lazar, Clara Yuh, Robert C Bucelli, Brian S Appleby, Gregory S Day

2020-Current year OA Pubs

No abstract provided.

What Clinical Trials Are Needed For Treatment Of Leiomyosarcoma?, Bernd Kasper, Lorenzo D'Ambrosio, Elizabeth J Davis, Matthew Ingham, Javier Martin Broto, Jonathan C Trent, Winan J Van Houdt, Brian A Van Tine

2020-Current year OA Pubs

Leiomyosarcoma is one of the most common subtypes of soft tissue sarcomas accounting for approximately 20% of sarcomas. As leiomyosarcoma patients frequently develop metastatic disease, effective systemic therapies are needed to improve clinical outcomes. The overall activity of the currently available conventional systemic therapies and the prognosis of patients with advanced and/or metastatic disease are poor. As such, the treatment of this patient population remains challenging. As a result, there is a clear unmet medical need, and designing and performing meaningful clinical studies are of utmost importance to improve the prognosis of this patient group. Therefore, the aim of this …

Social Isolation And Incident Heart Failure Hospitalization In Older Women: Women's Health Initiative Study Findings, Crystal W Cené, Xiaoyan Iris Leng, Khushnood Faraz, Matthew Allison, Khadijah Breathett, Chloe Bird, Mace Coday, Giselle Corbie-Smith, Randi Foraker, Nkechinyere N Ijioma, Milagros C Rosal, Shawnita Sealy-Jefferson, Tetyana P Shippee, Candyce H Kroenke

Open Access Publications

Background The association of social isolation or lack of social network ties in older adults is unknown. This knowledge gap is important since the risk of heart failure (HF) and social isolation increase with age. The study examines whether social isolation is associated with incident HF in older women, and examines depressive symptoms as a potential mediator and age and race and ethnicity as effect modifiers. Methods and Results This study included 44 174 postmenopausal women of diverse race and ethnicity from the WHI (Women's Health Initiative) study who underwent annual assessment for HF adjudication from baseline enrollment (1993-1998) through …

Failure To Detect Mutations In U2af1 Due To Changes In The Grch38 Reference Sequence, Christopher A Miller, Jason R Walker, Travis L Jensen, William F Hooper, Robert S Fulton, Jeffrey S Painter, Mikkael A Sekeres, Timothy J Ley, David H Spencer, Johannes B Goll, Matthew J Walter

2020-Current year OA Pubs

The U2AF1 gene is a core part of mRNA splicing machinery and frequently contains somatic mutations that contribute to oncogenesis in myelodysplastic syndrome, acute myeloid leukemia, and other cancers. A change introduced in the GRCh38 version of the human reference build prevents detection of mutations in this gene, and others, by variant calling pipelines. This study describes the problem in detail and shows that a modified GRCh38 reference build with unchanged coordinates can be used to ameliorate the issue.

International Stroke Genetics Consortium Recommendations For Studies Of Genetics Of Stroke Outcome And Recovery, Arne G Lindgren, Jin-Moo Lee, Et Al

2020-Current year OA Pubs

Numerous biological mechanisms contribute to outcome after stroke, including brain injury, inflammation, and repair mechanisms. Clinical genetic studies have the potential to discover biological mechanisms affecting stroke recovery in humans and identify intervention targets. Large sample sizes are needed to detect commonly occurring genetic variations related to stroke brain injury and recovery. However, this usually requires combining data from multiple studies where consistent terminology, methodology, and data collection timelines are essential. Our group of expert stroke and rehabilitation clinicians and researchers with knowledge in genetics of stroke recovery here present recommendations for harmonizing phenotype data with focus on measures suitable …

Prolonged Response Of Recurrent Idh-Wild-Type Glioblastoma To Laser Interstitial Thermal Therapy With Pembrolizumab, Helen Hwang, Jiayi Huang, Karam Khaddour, Omar H Butt, George Ansstas, Jie Chen, Ruth Gn Katumba, Albert H Kim, Eric C Leuthardt, Jian L Campian

2020-Current year OA Pubs

Despite the improved understanding of the molecular and genetic heterogeneity of glioblastoma, there is still an unmet need for better therapeutics, as treatment approaches have remained unchanged in recent years. Research into the role of the immune microenvironment has generated enthusiasm for testing immunotherapy (specifically, immune checkpoint inhibitors). However, to date, trials of immunotherapy in glioblastoma have not demonstrated a survival advantage. Combination approaches aimed at optimally inducing response to immune checkpoint inhibitors with radiotherapy are currently being investigated. Herein, the authors describe their experience of the potential benefit and clinical outcomes of using combination pembrolizumab (an immune checkpoint inhibitor) …

Moving The Needle: Directed Intervention By The American Society For Surgery Of The Hand Is Effective In Encouraging Diversity In Expert Panel Composition, Lauren Elisabeth Wessel, Ambika E Paulson, Elizabeth A Graesser, Amy M Moore, Christopher J Dy

2020-Current year OA Pubs

PURPOSE: Recent efforts have been made by the American Society for Surgery of the Hand to encourage female inclusion in expert panels. We hypothesized that female representation on expert panels has increased over the past decade and that a directed intervention by the American Society for Surgery of the Hand would be associated with an increased percentage of submissions with female panelists.

METHODS: We performed a retrospective analysis of Instructional Course Lecture and Symposium submissions for the 2011 through 2021 American Society for Surgery of the Hand Annual Meetings. Authorship was reviewed, and the gender of the proposed authors was …

Dmp1 Lineage Cells Contribute Significantly To Periosteal Lamellar Bone Formation Induced By Mechanical Loading But Are Depleted From The Bone Surface During Rapid Bone Formation, Taylor L Harris, Matthew J Silva

2020-Current year OA Pubs

Previous work has shown that osteoprogenitor cells (Prx1+) and pre-osteoblasts (Osx+) contribute to mechanical loading-induced bone formation. However, the role of mature Dmp1-expressing osteoblasts has not been reported. In this study we assessed the contribution of osteoblast lineage cells to bone formation at an early time point following mechanical loading (day 8 from onset of loading). We labeled Osx-expressing and Dmp1-expressing cells in inducible Osx and Dmp1 reporter mice (iOsx-Ai9, iDmp1-Ai9), respectively, 3 weeks before loading. Mice were then loaded daily for 5 days (days 1-5) and were dosed with 5-ethynyl-2'-deoxyuridine (EdU) in their drinking water until euthanasia on day …

Risk Of Intracranial Haemorrhage And Ischaemic Stroke After Convexity Subarachnoid Haemorrhage In Cerebral Amyloid Angiopathy: International Individual Patient Data Pooled Analysis, Isabel Charlotte Hostettler, Diane Aum, Gregory Joseph Zipfel, Et Al.

2020-Current year OA Pubs

OBJECTIVE: To investigate the frequency, time-course and predictors of intracerebral haemorrhage (ICH), recurrent convexity subarachnoid haemorrhage (cSAH), and ischemic stroke after cSAH associated with cerebral amyloid angiopathy (CAA).

METHODS: We performed a systematic review and international individual patient-data pooled analysis in patients with cSAH associated with probable or possible CAA diagnosed on baseline MRI using the modified Boston criteria. We used Cox proportional hazards models with a frailty term to account for between-cohort differences.

RESULTS: We included 190 patients (mean age 74.5 years; 45.3% female) from 13 centers with 385 patient-years of follow-up (median 1.4 years). The risks of each …

The Degenerative Impact Of Hyperglycemia On The Structure And Mechanics Of Developing Murine Intervertebral Discs, Marianne Lintz, Remy E Walk, Simon Y Tang, Lawrence J Bonassar

2020-Current year OA Pubs

INTRODUCTION: Diabetes has long been implicated as a major risk factor for intervertebral disc (IVD) degeneration, interfering with molecular signaling and matrix biochemistry, which ultimately aggravates the progression of the disease. Glucose content has been previously shown to influence structural and compositional changes in engineered discs in vitro, impeding fiber formation and mechanical stability.

METHODS: In this study, we investigated the impact of diabetic hyperglycemia on young IVDs by assessing biochemical composition, collagen fiber architecture, and mechanical behavior of discs harvested from 3- to 4-month-old db/db mouse caudal spines.

RESULTS: We found that discs taken from diabetic mice with elevated …

Fragile X Mental Retardation Protein And Cerebral Expression Of Metabotropic Glutamate Receptor Subtype 5 In Men With Fragile X Syndrome: A Pilot Study, James Robert Brašić, Jack Alexander Goodman, Ayon Nandi, David S Russell, Danna Jennings, Olivier Barret, Samuel D Martin, Keith Slifer, Thomas Sedlak, Anil Kumar Mathur, John P Seibyl, Elizabeth M Berry-Kravis, Dean F Wong, Dejan B Budimirovic

Open Access Publications

Multiple lines of evidence suggest that a deficiency of Fragile X Mental Retardation Protein (FMRP) mediates dysfunction of the metabotropic glutamate receptor subtype 5 (mGluR

Acquired Hydrocephalus Is Associated With Neuroinflammation, Progenitor Loss, And Cellular Changes In The Subventricular Zone And Periventricular White Matter, Maria Garcia-Bonilla, Leandro Castaneyra-Ruiz, Sarah Zwick, Michael Talcott, Ayodamola Otun, Albert M Isaacs, Diego M Morales, David D Limbrick, James P Mcallister

2020-Current year OA Pubs

BACKGROUND: Hydrocephalus is a neurological disease with an incidence of 80-125 per 100,000 births in the United States. Neuropathology comprises ventriculomegaly, periventricular white matter (PVWM) alterations, inflammation, and gliosis. We hypothesized that hydrocephalus in a pig model is associated with subventricular and PVWM cellular alterations and neuroinflammation that could mimic the neuropathology described in hydrocephalic infants.

METHODS: Hydrocephalus was induced by intracisternal kaolin injections in 35-day old female pigs (n = 7 for tissue analysis, n = 10 for CSF analysis). Age-matched sham controls received saline injections (n = 6). After 19-40 days, MRI scanning was performed to measure the …

Care Team And Practice-Level Implementation Strategies To Optimize Pediatric Collaborative Care: Study Protocol For A Cluster-Randomized Hybrid Type Iii Trial, David J Kolko, Elizabeth A Mcguier, Renee Turchi, Eileen Thompson, Satish Iyengar, Shawna N Smith, Kimberly Hoagwood, Celeste Liebrecht, Ian M Bennett, Byron J Powell, Kelly Kelleher, Maria Silva, Amy M Kilbourne

2020-Current year OA Pubs

BACKGROUND: Implementation facilitation is an effective strategy to support the implementation of evidence-based practices (EBPs), but our understanding of multilevel strategies and the mechanisms of change within the "black box" of implementation facilitation is limited. This implementation trial seeks to disentangle and evaluate the effects of facilitation strategies that separately target the care team and leadership levels on implementation of a collaborative care model in pediatric primary care. Strategies targeting the provider care team (TEAM) should engage team-level mechanisms, and strategies targeting leaders (LEAD) should engage organizational mechanisms.

METHODS: We will conduct a hybrid type 3 effectiveness-implementation trial in a …

Artificial Intelligence In Mammographic Phenotyping Of Breast Cancer Risk: A Narrative Review, Aimilia Gastounioti, Shyam Desai, Vinayak S Ahluwalia, Emily F Conant, Despina Kontos

2020-Current year OA Pubs

BACKGROUND: Improved breast cancer risk assessment models are needed to enable personalized screening strategies that achieve better harm-to-benefit ratio based on earlier detection and better breast cancer outcomes than existing screening guidelines. Computational mammographic phenotypes have demonstrated a promising role in breast cancer risk prediction. With the recent exponential growth of computational efficiency, the artificial intelligence (AI) revolution, driven by the introduction of deep learning, has expanded the utility of imaging in predictive models. Consequently, AI-based imaging-derived data has led to some of the most promising tools for precision breast cancer screening.

MAIN BODY: This review aims to synthesize the …

The Social Cerebellum: A Large-Scale Investigation Of Functional And Structural Specificity And Connectivity, Athanasia Metoki, Yin Wang, Ingrid R Olson

2020-Current year OA Pubs

The cerebellum has been traditionally disregarded in relation to nonmotor functions, but recent findings indicate it may be involved in language, affective processing, and social functions. Mentalizing, or Theory of Mind (ToM), is the ability to infer mental states of others and this skill relies on a distributed network of brain regions. Here, we leveraged large-scale multimodal neuroimaging data to elucidate the structural and functional role of the cerebellum in mentalizing. We used functional activations to determine whether the cerebellum has a domain-general or domain-specific functional role, and effective connectivity and probabilistic tractography to map the cerebello-cerebral mentalizing network. We …

Dietary Patterns Are Associated With Improved Ovarian Reserve In Overweight And Obese Women: A Cross-Sectional Study Of The Lifestyle And Ovarian Reserve (Lore) Cohort, Ashley M Eskew, Bronwyn S Bedrick, Jorge E Chavarro, Joan K Riley, Emily S Jungheim

2020-Current year OA Pubs

BACKGROUND: Growing evidence suggests that adherence to certain dietary patterns is associated with improved fecundity and reproductive outcomes in the general population and infertile couples assisted reproductive treatments. The objective of this study was to assess if dietary patterns are associated with ovarian reserve in reproductive age women without a history of infertility.

METHODS: This was a cross-sectional study of 185 women in the Lifestyle and Ovarian Reserve (LORe) cohort. Women aged 18-44 without a history of infertility were recruited from the local community at an academic medical center. Subjects completed validated food frequency and physical activity questionnaires to assess …

Repeated Endo-Tracheal Tube Disconnection Generates Pulmonary Edema In A Model Of Volume Overload: An Experimental Study, Bhushan H Katira, Doreen Engelberts, Sheena Bouch, Jordan Fliss, Luca Bastia, Kohei Osada, Kim A Connelly, Marcelo B P Amato, Niall D Ferguson, Wolfgang M Kuebler, Brian P Kavanagh, Laurent J Brochard, Martin Post

2020-Current year OA Pubs

BACKGROUND: An abrupt lung deflation in rodents results in lung injury through vascular mechanisms. Ventilator disconnections during endo-tracheal suctioning in humans often cause cardio-respiratory instability. Whether repeated disconnections or lung deflations cause lung injury or oedema is not known and was tested here in a porcine large animal model.

METHODS: Yorkshire pigs (~ 12 weeks) were studied in three series. First, we compared PEEP abruptly deflated from 26 cmH

RESULTS: As compared to PEEP 5 cmH

CONCLUSION: Single abrupt deflation from high PEEP, and repeated short deflations from moderate PEEP cause pulmonary oedema, impaired oxygenation, and increased PVR, in this …

Sustained Efficacy And Safety Of Burosumab, A Monoclonal Antibody To Fgf23, In Children With X-Linked Hypophosphatemia, Agnès Linglart, Erik A Imel, Michael P Whyte, Anthony A Portale, Wolfgang Högler, Annemieke M Boot, Raja Padidela, William Van't Hoff, Gary S Gottesman, Angel Chen, Alison Skrinar, Mary Scott Roberts, Thomas O Carpenter

2020-Current year OA Pubs

PURPOSE: In X-linked hypophosphatemia (XLH), excess fibroblast growth factor-23 causes hypophosphatemia and low calcitriol, leading to musculoskeletal disease with clinical consequences. XLH treatment options include conventional oral phosphate with active vitamin D, or monotherapy with burosumab, a monoclonal antibody approved to treat children and adults with XLH. We have previously reported outcomes up to 64 weeks, and here we report safety and efficacy follow-up results up to 160 weeks from an open-label, multicenter, randomized, dose-finding trial of burosumab for 5- to 12-year-old children with XLH.

METHODS: After 1 week of conventional therapy washout, patients were randomized 1:1 to burosumab every …

The Prevalance Of Binge Eating Disorder And Associated Psychiatric And Substance Use Disorders In A Student Population In Kenya - Towards A Public Health Approach, Victoria N Mutiso, David M Ndetei, Esther N Muia, Rita K Alietsi, Lydia Onsinyo, Frida Kameti, Monicah Masake, Christine Musyimi, Daniel Mamah

2020-Current year OA Pubs

INTRODUCTION: Kenya in particular and Africa in general lack data on Binge Eating Disorder (BED). The overarching objective of this study is to fill that gap. Kenyans may not be aware that BED exists when a "very good" appetite is considered a sign of good health, especially if food is available either at home, in fast food shops or when communally eating together, a very common cultural practice. On the other hand where there is relatively insufficient food, it is not expected that one could be having a problem of eating too much.

METHOD: We administered the following tools and …

Hydraulic Permeability And Compressive Properties Of Porcine And Human Synovium, Milad Rohanifar, Benjamin B Johnston, Alexandra L Davis, Young Guang, Kayla Nommensen, James A J Fitzpatrick, Christine N Pham, Lori A Setton

2020-Current year OA Pubs

The synovium is a multilayer connective tissue separating the intra-articular spaces of the diarthrodial joint from the extra-synovial vascular and lymphatic supply. Synovium regulates drug transport into and out of the joint, yet its material properties remain poorly characterized. Here, we measured the compressive properties (aggregate modulus, Young's modulus, and Poisson's ratio) and hydraulic permeability of synovium with a combined experimental-computational approach. A compressive aggregate modulus and Young's modulus for the solid phase of synovium were quantified from linear regression of the equilibrium confined and unconfined compressive stress upon strain, respectively (H

Therapeutic Efficacy Of 177lu-Labeled A20fmdv2 Peptides Targeting Ανβ6, Truc Thao Huynh, Sreeja Sreekumar, Cedric Mpoy, Buck Edward Rogers

2020-Current year OA Pubs

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Filtering Respiratory Motion Artifact From Resting State Fmri Data In Infant And Toddler Populations, Sydney Kaplan, Dominique Meyer, Dimitrios Alexopoulos, Deanna M Barch, Adam T Eggebrecht, Jeanette K Kenley, Cynthia E Rogers, Muriah D Wheelock, Christopher D Smyser, Et Al.

2020-Current year OA Pubs

The importance of motion correction when processing resting state functional magnetic resonance imaging (rs-fMRI) data is well-established in adult cohorts. This includes adjustments based on self-limited, large amplitude subject head motion, as well as factitious rhythmic motion induced by respiration. In adults, such respiration artifact can be effectively removed by applying a notch filter to the motion trace, resulting in higher amounts of data retained after frame censoring (e.g., "scrubbing") and more reliable correlation values. Due to the unique physiological and behavioral characteristics of infants and toddlers, rs-fMRI processing pipelines, including methods to identify and remove colored noise due to …

Enhancing Task Fmri Preprocessing Via Individualized Model-Based Filtering Of Intrinsic Activity Dynamics, Matthew F Singh, Anxu Wang, Michael Cole, Shinung Ching, Todd S Braver

2020-Current year OA Pubs

Brain responses recorded during fMRI are thought to reflect both rapid, stimulus-evoked activity and the propagation of spontaneous activity through brain networks. In the current work, we describe a method to improve the estimation of task-evoked brain activity by first "filtering-out the intrinsic propagation of pre-event activity from the BOLD signal. We do so using Mesoscale Individualized NeuroDynamic (MINDy; Singh et al. 2020b) models built from individualized resting-state data to subtract the propagation of spontaneous activity from the task-fMRI signal (MINDy-based Filtering). After filtering, time-series are analyzed using conventional techniques. Results demonstrate that this simple operation significantly improves the statistical …

Relationships Between Correlated Spikes, Oxygen And Lfp In The Resting-State Primate, Jingfeng M Li, Benjamin T Acland, Alexander S Brenner, William J Bentley, Lawrence H Snyder

2020-Current year OA Pubs

Resting-state functional MRI (rsfMRI) provides a view of human brain organization based on correlation patterns of blood oxygen level dependent (BOLD) signals recorded across the whole brain. The neural basis of resting-state BOLD fluctuations and their correlation remains poorly understood. We simultaneously recorded oxygen level, spikes, and local field potential (LFP) at multiple sites in awake, resting monkeys. Following a spike, the average local oxygen and LFP voltage responses each resemble a task-driven BOLD response, with LFP preceding oxygen by 0.5 s. Between sites, features of the long-range correlation patterns of oxygen, LFP, and spikes are similar to features seen …

Prevention Is Political: Political Party Affiliation Predicts Perceived Risk And Prevention Behaviors For Covid-19, Marc T Kiviniemi, Heather Orom, Jennifer L Hay, Erika A Waters

2020-Current year OA Pubs

BACKGROUND: Many US politicians have provided mixed messages about the risks posed by SARS-CoV-2/COVID-19 and whether and to what extent prevention practices should be put in place to prevent transmission. This politicization of the virus and pandemic may affect individuals' risk perceptions and willingness to take precautions. We examined how political party affiliation relates to risk perception for one's own and other people's likelihood of SARS-CoV-2 infection/COVID-19 illness.

METHODS: We surveyed members of a nationally-representative, probability-sampling based survey panel (N = 410) to examine their risk perceptions, precautionary behaviors, and political party affiliation.

RESULTS: The more strongly one identified as …

Intracranial Internal Carotid Artery Calcification Is Not Predictive Of Future Cognitive Decline, Farzaneh Rahmani, Marina Nguyen, Charles D Chen, Nicole Mckay, Aylin Dincer, Nelly Joseph-Mathurin, Gengsheng Chen, Jingxia Liu, Hilary L P Orlowski, John C Morris, Tammie L S Benzinger

2020-Current year OA Pubs

BACKGROUND: Intracranial internal carotid artery (ICA) calcification is a common incidental finding in non-contrast head CT. We evaluated the predictive value of ICAC (ICAC) for future risk of cognitive decline and compared the results with conventional imaging biomarkers of dementia.

METHODS: In a retrospective observational cohort, we included 230 participants with a PET-CT scan within 18 months of a baseline clinical assessment and longitudinal imaging assessments. Intracranial ICAC was quantified on baseline CT scans using the Agatson calcium score, and the association between baseline ICA calcium scores and the risk of conversion from a CDR of zero in baseline to …

Single-Agent Mosunetuzumab Shows Durable Complete Responses In Patients With Relapsed Or Refractory B-Cell Lymphomas: Phase I Dose-Escalation Study, Lihua E Budde, Nancy L Bartlett, Et Al

2020-Current year OA Pubs

PURPOSE: Mosunetuzumab is a bispecific antibody targeting CD20 and CD3 that redirects T cells to engage and eliminate malignant B cells and is being developed for relapsed or refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHLs).

METHODS: This first-in-human trial (ClinicalTrials.gov identifier: NCT02500407) evaluated the safety and tolerability and efficacy of mosunetuzumab in patients with R/R B-NHL and established the recommended phase II dose. Data from dose escalation are presented. Single-agent mosunetuzumab was administered intravenously in 3-week cycles, at full dose in cycle 1 day 1 (group A) or with ascending (step-up) doses during cycle 1 on days 1, 8, and 15 …