Medicine and Health Sciences Commons^™

Approaches To Aggressive B-Cell Lymphomas In Less Fit Patients, Nancy L Bartlett

2020-Current year OA Pubs

Treating unfit patients with aggressive B-cell lymphoma poses the dilemma of balancing potential cure while minimizing toxicity because of frailty and comorbidities. Age greater than 80 years and common comorbidities such as cardiovascular disease and poorly controlled diabetes mellitus often preclude the use of full-dose anthracyclines and steroids, the backbones of standard regimens for aggressive B-cell lymphomas. Assessing patient fitness remains subjective, with no consensus on best practice or how to integrate assessment tools into decision making. Incorporation of prephase steroids for all unfit patients may markedly improve performance status with consideration of standard dose therapy, especially in patients less …

Functional Genomic Analyses Uncover Apoe-Mediated Regulation Of Brain And Cerebrospinal Fluid Beta-Amyloid Levels In Parkinson Disease, Laura Ibanez, Jorge A Bahena, Chengran Yang, Umber Dube, Fabiana H G Farias, John P Budde, Kristy Bergmann, Carol Brenner-Webster, John C Morris, Richard J Perrin, Nigel J Cairns, John O'Donnell, Rebecca Miller, Albert A Davis, Paul Kotzbauer, Meghan C Campbell, Joel S Perlmutter, Oscar Harari, Carlos Cruchaga, Bruno A Benitez, Et Al.

2020-Current year OA Pubs

Alpha-synuclein is the main protein component of Lewy bodies, the pathological hallmark of Parkinson's disease. However, genetic modifiers of cerebrospinal fluid (CSF) alpha-synuclein levels remain unknown. The use of CSF levels of amyloid beta

Phase 1 Study Of The Mdm2 Antagonist Ro6839921 In Patients With Acute Myeloid Leukemia, Geoffrey L Uy, Sarit Assouline, Anne-Marie Young, Steven Blotner, Brian Higgins, Lin-Chi Chen, Karen Yee

2020-Current year OA Pubs

In acute myeloid leukemia (AML), TP53 mutations and dysregulation of wild-type p53 is common and supports an MDM2 antagonist as a therapy. RO6839921 is an inactive pegylated prodrug of the oral MDM2 antagonist idasanutlin (active principle [AP]) that allows for IV administration. This phase 1 monotherapy study evaluated the safety, pharmacokinetics, and pharmacodynamics of RO6839921 in patients with AML. Primary objectives identified dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD). Secondary objectives assessed pharmacokinetic, pharmacodynamic, and antileukemic activity. A total of 26 patients received 120-300 mg AP of idasanutlin. The MTD was 200 mg, with DLTs at 250 (2/8 patients) …

Regional Correlation Of Biochemical Measures Of Amyloid And Tau Phosphorylation In The Brain, Kanta Horie, Nicolas R Barthélemy, Nipun Mallipeddi, Yan Li, Erin E Franklin, Richard J Perrin, Randall J Bateman, Chihiro Sato

2020-Current year OA Pubs

Alzheimer's disease (AD) neuropathologic change is characterized by amyloid plaques and neurofibrillary tangles (NFTs) that consist of aggregated amyloid beta (Abeta) and hyperphosphorylated tau proteins (p-tau), respectively. Although the global relationship between Abeta and p-tau has been studied for decades, it is still unclear whether a regional correlation exists between Abeta and p-tau in the human brain. Recent studies in cerebrospinal fluid (CSF) have suggested that tau phosphorylation at specific sites such as T217 is modified at an early stage of AD when amyloid plaques become detectable. We applied biochemical and mass spectrometry methods in human brain samples with and …

Proteogenomic Characterization Reveals Therapeutic Vulnerabilities In Lung Adenocarcinoma, Michael A. Gillette, Song Cao, Yize Li, Wen-Wei Liang, Michael C Wendl, Ramaswamy Govindan, Et Al.

2020-Current year OA Pubs

To explore the biology of lung adenocarcinoma (LUAD) and identify new therapeutic opportunities, we performed comprehensive proteogenomic characterization of 110 tumors and 101 matched normal adjacent tissues (NATs) incorporating genomics, epigenomics, deep-scale proteomics, phosphoproteomics, and acetylproteomics. Multi-omics clustering revealed four subgroups defined by key driver mutations, country, and gender. Proteomic and phosphoproteomic data illuminated biology downstream of copy number aberrations, somatic mutations, and fusions and identified therapeutic vulnerabilities associated with driver events involving KRAS, EGFR, and ALK. Immune subtyping revealed a complex landscape, reinforced the association of STK11 with immune-cold behavior, and underscored a potential immunosuppressive role of neutrophil degranulation. …

Natural History Of Geographic Atrophy Secondary To Age-Related Macular Degeneration: Results From The Prospective Proxima A And B Clinical Trials, Nancy Holekamp, Charles C Wykoff, Steffen Schmitz-Valckenberg, Jordi Monés, Eric H Souied, Hugh Lin, Melvin D Rabena, Ronald A Cantrell, Erin C Henry, Fan Tang, Balakumar Swaminathan, Jillian Martin, Daniela Ferrara, Giovanni Staurenghi

2020-Current year OA Pubs

PURPOSE: To better characterize visual function decline and geographic atrophy (GA) progression secondary to age-related macular degeneration (AMD).

DESIGN: Proxima A (NCT02479386)/Proxima B (NCT02399072) were global, prospective, noninterventional, observational clinical trials.

PARTICIPANTS: Eligible patients were aged ≥50 years. Patients in Proxima A had bilateral GA without choroidal neovascularization (CNV) in either eye (N = 295). Patients in Proxima B had GA without CNV in the study eye and CNV±GA in the fellow eye (fellow eye CNV cohort, n = 168) or GA without CNV in the study eye, no CNV/GA in the fellow eye (fellow eye intermediate AMD cohort, n …

Phase 2 Study Of Cemiplimab In Patients With Metastatic Cutaneous Squamous Cell Carcinoma: Primary Analysis Of Fixed-Dosing, Long-Term Outcome Of Weight-Based Dosing, Danny Rischin, Leonel Hernandez-Aya, Et Al

2020-Current year OA Pubs

BACKGROUND: Cemiplimab, a high-affinity, potent human immunoglobulin G4 monoclonal antibody to programmed cell death-1 demonstrated antitumor activity in a Phase 1 advanced cutaneous squamous cell carcinoma (CSCC) expansion cohort (NCT02383212) and the pivotal Phase 2 study (NCT02760498). Here we report the primary analysis of fixed dose cemiplimab 350 mg intravenously every 3 weeks (Q3W) (Group 3) and provide a longer-term update after the primary analysis of weight-based cemiplimab 3 mg/kg intravenously every 2 weeks (Q2W) (Group 1) among metastatic CSCC (mCSCC) patients in the pivotal study (NCT02760498).

METHODS: The primary objective for each group was objective response rate (ORR) per …

Prevalence Of Clinically Actionable Disease Variants In Exceptionally Long-Lived Families, Paige Carlson, Mary K Wojczynski, Todd Druley, Joseph H Lee, Joseph M Zmuda, Bharat Thyagarajan

2020-Current year OA Pubs

BACKGROUND: Phenotypic expression of pathogenic variants in individuals with no family history of inherited disorders remains unclear.

METHODS: We evaluated the prevalence of pathogenic variants in 25 genes associated with Mendelian-inherited disorders in 3015 participants from 485 families in the Long Life Family Study (LLFS). Boot-strapping and Fisher's exact test were used to determine whether allele frequencies in LLFS were significantly different from the allele frequencies reported in publicly available genomic databases.

RESULTS: The proportions of pathogenic autosomal dominant mutation carriers in BRCA1 and SDHC in LLFS study participants were similar to those reported in publicly available genomic databases (0.03% …

Breast Cancer Risk, Worry, And Anxiety: Effect On Patient Perceptions Of False-Positive Screening Results, Janie M. Lee, Kathryn P. Lowry, Jessica E. Cott Chubiz, J. Shannon Swan, Tina Motazedi, Elkan F. Halpern, Anna N. A. Tosteson, G. Scott Gazelle, Karen Donelan

2020-Current year OA Pubs

OBJECTIVE: The impact of mammography screening recall on quality-of-life (QOL) has been studied in women at average risk for breast cancer, but it is unknown whether these effects differ by breast cancer risk level. We used a vignette-based survey to evaluate how women across the spectrum of breast cancer risk perceive the experience of screening recall.

METHODS: Women participating in mammography or breast MRI screening were recruited to complete a vignette-based survey. Using a numerical rating scale (0-100), women rated QOL for hypothetical scenarios of screening recall, both before and after benign results were known. Lifetime breast cancer risk was …

Laser Ablation Of Abnormal Neurological Tissue Using Robotic Neuroblate System (Laantern): Procedural Safety And Hospitalization, Robert C. Rennert, Usman Khan, Jiri Bartek, Stephen B. Tatter, Melvin Field, Brian Toyota, Peter E. Fecci, Kevin Judy, Alireza M. Mohammadi, Patrick Landazuri, Andrew E. Sloan, Albert H. Kim, Eric C. Leuthardt, Clark C. Chen

2020-Current year OA Pubs

BACKGROUND: Stereotactic laser ablation (SLA) has demonstrated potential utility for a spectrum of difficult to treat neurosurgical pathologies in multiple small and/or retrospective single-institutional series. Here, we present the safety profile of SLA of intracranial lesions from the Laser Ablation of Abnormal Neurological Tissue using Robotic NeuroBlate System (LAANTERN; Monteris Medical) multi-institutional, international prospective observational registry.

OBJECTIVE: To determine the procedural safety of SLA for intracranial lesions.

METHODS: Prospective procedural safety and hospitalization data from the first 100 treated LAANTERN patients was collected and analyzed.

RESULTS: Mean age and baseline Karnofsky Performance Status (KPS) were 51(± 17) yr and 83(± …

Negative Pressure Wound Therapy With Instillation: International Consensus Guidelines Update., Paul J Kim, Christopher E Attinger, Thomas Constantine, Brett D Crist, Elizabeth Faust, Christoph R Hirche, Lawrence A Lavery, Valerie J Messina, Norihiko Ohura, Laurie J Punch, Garrett A Wirth, Ibby Younis, Luc Téot

2020-Current year OA Pubs

The use of negative pressure wound therapy with instillation and dwell time (NPWTi-d) has gained wider adoption and interest due in part to the increasing complexity of wounds and patient conditions. Best practices for the use of NPWTi-d have shifted in recent years based on a growing body of evidence and expanded worldwide experience with the technology. To better guide the use of NPWTi-d with all dressing and setting configurations, as well as solutions, there is a need to publish updated international consensus guidelines, which were last produced over 6 years ago. An international, multidisciplinary expert panel of clinicians was …

Who Benefits From A Prostate Rectal Spacer? Secondary Analysis Of A Phase Iii Trial, Thomas J. Quinn, Walter Bosch, Et Al.

2020-Current year OA Pubs

PURPOSE: Previously a phase III trial of a hydrogel rectal spacer during prostate radiation therapy found decreased toxicity and a clinically significant improvement in bowel quality of life (QOL) at 3 years by the Expanded Prostate Cancer Index. We performed a secondary analysis to identify men less likely to benefit.

METHODS AND MATERIALS: Clinical and dosimetric data for the 222 patients enrolled on the SpaceOAR phase III trial were analyzed. The volume of rectum treated to 70 Gy (V70) and the quantitative analysis of normal tissue effects in the clinic (QUANTEC) rectal dose goals were used as surrogates for clinical …