Digital Commons Network^™

Associations Between Atrial Cardiopathy And Cerebral Amyloid: The Aric-Pet Study, Michelle C Johansen, Thomas H Mosley, David S Knopman, Dean F Wong, Chiadi Ndumele, Amil M Shah, Scott D Solomon, Rebecca F Gottesman

Open Access Publications

Background Atrial fibrillation (AF) is a risk factor for cognitive decline, possibly from silent brain infarction. Left atrial changes in structure or function (atrial cardiopathy) can lead to AF but may impact cognition independently. It is unknown if AF or atrial cardiopathy also acts on Alzheimer disease-specific mechanisms, such as deposition of β-amyloid. Methods and Results A total of 316 dementia-free participants from the ARIC (Atherosclerosis Risk in Communities) study underwent florbetapir positron emission tomography, electrocardiography, and 2-dimensional echocardiography. Atrial cardiopathy was defined as ≥1: (1) left atrial volume index >34 mL/m

Positive Information Facilitates Response Inhibition In Older Adults Only When Emotion Is Task-Relevant, Samantha E Williams, Eric J Lenze, Jill D Waring

Open Access Publications

Emotional information is integral to everyday life and impacts a variety of cognitive abilities including response inhibition, a critical skill for maintaining appropriate and flexible behaviour. However, reported effects of emotion on response inhibition are inconsistent in younger adults, and very limited in older adults. Effects of aging are especially relevant because emotion regulation improves with aging despite declining inhibitory control over neutral information. Across three studies, we assessed the impact of emotional facial expressions on response inhibition in younger and older adults while manipulating attention to task stimuli. Emotional faces (versus neutral faces) altered response inhibition only when task …

The Perceived Challenge Of Everyday Technologies In Sweden, The United States And England: Exploring Differential Item Functioning In The Everyday Technology Use Questionnaire, Sarah Wallcook, Camilla Malinowsky, Louise Nygård, Georgina Charlesworth, Jenica Lee, Ryan Walsh, Sophie Gaber, Anders Kottorp

Open Access Publications

No abstract provided.

Severe Immunosuppression And Not A Cytokine Storm Characterizes Covid-19 Infections, Kenneth E Remy, Monty Mazer, David A Striker, Ali H Ellebedy, Andrew H Walton, Jacqueline Unsinger, Teresa M Blood, Philip A Mudd, Daehan J Yi, Daniel A Mannion, Dale F Osborne, R Scott Martin, Nitin J Anand, James P Bosanquet, Jane Blood, Anne M Drewry, Charles C Caldwell, Isaiah R Turnbull, Scott C Brakenridge, Lyle L Moldwawer, Richard S Hotchkiss

Open Access Publications

COVID-19-associated morbidity and mortality have been attributed to a pathologic host response. Two divergent hypotheses have been proposed: hyperinflammatory cytokine storm; and failure of host protective immunity that results in unrestrained viral dissemination and organ injury. A key explanation for the inability to address this controversy has been the lack of diagnostic tools to evaluate immune function in COVID-19 infections. ELISpot, a highly sensitive, functional immunoassay, was employed in 27 patients with COVID-19, 51 patients with sepsis, 18 critically ill nonseptic (CINS) patients, and 27 healthy control volunteers to evaluate adaptive and innate immune status by quantitating T cell IFN-ɣ …

Genetic Variants And Functional Pathways Associated With Resilience To Alzheimer's Disease, Logan Dumitrescu, Carlos Cruchaga, Et Al

Open Access Publications

Approximately 30% of older adults exhibit the neuropathological features of Alzheimer's disease without signs of cognitive impairment. Yet, little is known about the genetic factors that allow these potentially resilient individuals to remain cognitively unimpaired in the face of substantial neuropathology. We performed a large, genome-wide association study (GWAS) of two previously validated metrics of cognitive resilience quantified using a latent variable modelling approach and representing better-than-predicted cognitive performance for a given level of neuropathology. Data were harmonized across 5108 participants from a clinical trial of Alzheimer's disease and three longitudinal cohort studies of cognitive ageing. All analyses were run …

Molecular And Clinicopathologic Features Of Gliomas Harboring Ntrk Fusions, Matthew Torre, Sonika Dahiya, Et Al

Open Access Publications

Fusions involving neurotrophic tyrosine receptor kinase (NTRK) genes are detected in ≤2% of gliomas and can promote gliomagenesis. The remarkable therapeutic efficacy of TRK inhibitors, which are among the first Food and Drug Administration-approved targeted therapies for NTRK-fused gliomas, has generated significant clinical interest in characterizing these tumors. In this multi-institutional retrospective study of 42 gliomas with NTRK fusions, next generation DNA sequencing (n = 41), next generation RNA sequencing (n = 1), RNA-sequencing fusion panel (n = 16), methylation profile analysis (n = 18), and histologic evaluation (n = 42) were performed. All infantile NTRK-fused gliomas (n = 7) …

Association Of Interleukin 7 Immunotherapy With Lymphocyte Counts Among Patients With Severe Coronavirus Disease 2019 (Covid-19), Pierre Francois Laterre, Bruno François, Christine Collienne, Philippe Hantson, Robin Jeannet, Kenneth E. Remy, Richard S. Hotchkiss

Open Access Publications

No abstract provided.

Systemic Inflammatory Response Syndrome In Patients With Acute Obstructive Upper Tract Urinary Stone: A Risk Factor For Urgent Renal Drainage And Revisit To The Emergency Department, Spencer Larkin, Jeremy Johnson, Trisha Venkatesh, Joel Vetter, Ramakrishna Venkatesh

Open Access Publications

BACKGROUND: In patients seen in the emergency department (ED) with acute stone obstruction many risk factors that indicate need for urgent renal drainage are known. However, in patients discharged from ED without renal drainage factors that can minimize revisit to the emergency department are not fully identified. We evaluated SIRS (systemic inflammatory response syndrome) as a risk factor for urgent renal drainage and revisit to the ED in patients with acute stone colic during their ED visit.

METHODS: Retrospective review was performed of patients presenting to a tertiary academic emergency department (ED) from an obstructing ureteral or UPJ stone with …

Bosutinib For Pretreated Patients With Chronic Phase Chronic Myeloid Leukemia: Primary Results Of The Phase 4 Byond Study, Andreas Hochhaus, Camille Abboud, Et Al

Open Access Publications

Bosutinib is approved for newly diagnosed Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML) and for Ph+ CP, accelerated (AP), or blast (BP) phase CML after prior treatment with tyrosine kinase inhibitors (TKIs). In the ongoing phase 4 BYOND study (NCT02228382), 163 CML patients resistant/intolerant to prior TKIs (n = 156 Ph+ CP CML, n = 4 Ph+ AP CML, n = 3 Ph-negative/BCR-ABL1+ CML) received bosutinib 500 mg once daily (starting dose). As of ≥1 year after last enrolled patient (median treatment duration 23.7 months), 56.4% of Ph+ CP CML patients remained on bosutinib. Primary endpoint of …

A Dose-Finding Phase 2 Study Of Single Agent Isatuximab (Anti-Cd38 Mab) In Relapsed/Refractory Multiple Myeloma, Joseph Mikhael, Ravi Vij, Et Al

Open Access Publications

A Phase 2 dose-finding study evaluated isatuximab, an anti-CD38 monoclonal antibody, in relapsed/refractory multiple myeloma (RRMM; NCT01084252). Patients with ≥3 prior lines or refractory to both immunomodulatory drugs and proteasome inhibitors (dual refractory) were randomized to isatuximab 3 mg/kg every 2 weeks (Q2W), 10 mg/kg Q2W(2 cycles)/Q4W, or 10 mg/kg Q2W. A fourth arm evaluated 20 mg/kg QW(1 cycle)/Q2W. Patients (N = 97) had a median (range) age of 62 years (38-85), 5 (2-14) prior therapy lines, and 85% were double refractory. The overall response rate (ORR) was 4.3, 20.0, 29.2, and 24.0% with isatuximab 3 mg/kg Q2W, 10 mg/kg …

Coronary Heart Disease And Mortality Following A Breast Cancer Diagnosis, Aixia Guo, Kathleen W Zhang, Kristi Reynolds, Randi E Foraker

Open Access Publications

BACKGROUND: Coronary heart disease (CHD) is a leading cause of morbidity and mortality for breast cancer survivors, yet the joint effect of adverse cardiovascular health (CVH) and cardiotoxic cancer treatments on post-treatment CHD and death has not been quantified.

METHODS: We conducted statistical and machine learning approaches to evaluate 10-year risk of these outcomes among 1934 women diagnosed with breast cancer during 2006 and 2007. Overall CVH scores were classified as poor, intermediate, or ideal for 5 factors, smoking, body mass index, blood pressure, glucose/hemoglobin A1c, and cholesterol from clinical data within 5 years prior to the breast cancer diagnosis. …

The Safety Of Combined Triple Drug Therapy With Ivermectin, Diethylcarbamazine And Albendazole In The Neglected Tropical Diseases Co-Endemic Setting Of Fiji: A Cluster Randomised Trial, Myra Hardy, Josaia Samuela, Mike Kama, Meciusela Tuicakau, Lucia Romani, Margot J. Whitfeld, Christopher L. King, Gary J. Weil, Anneke C. Grobler, Leanne J. Robinson, John M. Kaldor, Andrew C. Steer

Open Access Publications

Lymphatic filariasis has remained endemic in Fiji despite repeated mass drug administration using the well-established and safe combination of diethylcarbamazine and albendazole (DA) since 2002. In certain settings the addition of ivermectin to this combination (IDA) remains a safe strategy and is more efficacious. However, the safety has yet to be described in scabies and soil-transmitted helminth endemic settings like Fiji. Villages of Rotuma and Gau islands were randomised to either DA or IDA. Residents received weight-based treatment unblinded with standard exclusions. Participants were actively found and asked by a nurse about their health daily for the first two days …

Second-Line Lenvatinib In Patients With Recurrent Endometrial Cancer, Ignace Vergote, Matthew A Powell, Michael G Teneriello, David S Miller, Agustin A Garcia, Olga N Mikheeva, Mariusz Bidzinski, Cristina Ligia Cebotaru, Corina E Dutcus, Min Ren, Tadashi Kadowaki, Yasuhiro Funahashi, Richard T Penson

Open Access Publications

OBJECTIVE: This study assessed the efficacy of lenvatinib, a multitargeted tyrosine kinase inhibitor, as second-line therapy in patients with unresectable endometrial cancer. The primary end point was the objective response rate (ORR) as assessed by independent radiologic review (IRR). Secondary end points included median progression-free survival (PFS), overall survival (OS), and clinical benefit rate. Exploratory end points examined the association of baseline levels of plasma biomarkers (50 circulating cytokine and/or angiogenic factors measured by immunoassays) with efficacy outcomes.

METHODS: An international, open-label, single-arm, multicenter, phase 2 trial was conducted. Eligible patients had histologically confirmed unresectable endometrial cancer that relapsed after …

Decision-Making Based On 3d Printed Models In Laparoscopic Liver Resections With Intraoperative Ultrasound: A Prospective Observational Study, Jan Witowski, Andrzej Budzyński, Anna Grochowska, David H Ballard, Piotr Major, Mateusz Rubinkiewicz, Adriana Złahoda-Huzior, Tadeusz J Popiela, Mateusz Wierdak, Michał Pędziwiatr

Open Access Publications

OBJECTIVES: The aim of this study was to evaluate impact of 3D printed models on decision-making in context of laparoscopic liver resections (LLR) performed with intraoperative ultrasound (IOUS) guidance.

METHODS: Nineteen patients with liver malignances (74% were colorectal cancer metastases) were prospectively qualified for LLR or radiofrequency ablation in a single center from April 2017 to December 2018. Models were 3DP in all cases based on CT and facilitated optical visualization of tumors' relationships with portal and hepatic veins. Planned surgical extent and its changes were tracked after CT analysis and 3D model inspection, as well as intraoperatively using IOUS. …

Association Of Clinical Outcomes With Left Ventricular Assist Device Use By Bridge To Transplant Or Destination Therapy Intent: The Multicenter Study Of Maglev Technology In Patients Undergoing Mechanical Circulatory Support Therapy With Heartmate 3 (Momentum 3) Randomized Clinical Trial, Daniel J Goldstein, Akinobu Itoh, Et Al

Open Access Publications

Importance: Left ventricular assist devices (LVADs) are well established in the treatment of advanced heart failure, but it is unclear whether outcomes are different based on the intended goal of therapy in patients who are eligible vs ineligible for heart transplant.

Objective: To determine whether clinical outcomes in the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 (MOMENTUM 3) trial differed by preoperative categories of bridge to transplant (BTT) or bridge to transplant candidacy (BTC) vs destination therapy (DT).

Design, Setting, and Participants: This study was a prespecified secondary analysis of the MOMENTUM …

Distinct Inflammatory Profiles Distinguish Covid-19 From Influenza With Limited Contributions From Cytokine Storm, Philip A Mudd, Jackson S Turner, Daniel Reynolds, Diane Bender, Adrianus C M Boon, Stacey L House, Kenneth E Remy, Richard S Hotchkiss, Rachel M Presti, Jane A O'Halloran, William G Powderly, Ali H Ellebedy, Et Al

Open Access Publications

We pursued a study of immune responses in coronavirus disease 2019 (COVID-19) and influenza patients. Compared to patients with influenza, patients with COVID-19 exhibited largely equivalent lymphocyte counts, fewer monocytes, and lower surface human leukocyte antigen (HLA)-class II expression on selected monocyte populations. Furthermore, decreased HLA-DR on intermediate monocytes predicted severe COVID-19 disease. In contrast to prevailing assumptions, very few (7 of 168) patients with COVID-19 exhibited cytokine profiles indicative of cytokine storm syndrome. After controlling for multiple factors including age and sample time point, patients with COVID-19 exhibited lower cytokine levels than patients with influenza. Up-regulation of IL-6, G-CSF, …

Sars-Cov-2 Viral Rna Shedding For More Than 87 Days In An Individual With An Impaired Cd8+ T Cell Response, Jackson S Turner, Aaron Day, Wafaa B Alsoussi, Zhuoming Liu, Jane A O'Halloran, Rachel M Presti, Bruce K Patterson, Sean P J Whelan, Ali H Ellebedy, Philip A Mudd

Open Access Publications

Prolonged shedding of viral RNA occurs in some individuals following SARS-CoV-2 infection. We perform comprehensive immunologic evaluation of one individual with prolonged shedding. The case subject recovered from severe COVID-19 and tested positive for SARS-CoV-2 viral RNA repeatedly as many as 87 days after the first positive test, 97 days after symptom onset. The subject did not have any associated rise in anti-Spike protein antibody titers or plasma neutralization activity, arguing against re-infection. This index subject exhibited a profoundly diminished circulating CD8+ T cell population and correspondingly low SARS-CoV-2-specific CD8+ T cell responses when compared with a cohort of other …

End Of An Era Of Administering Erythropoiesis Stimulating Agents Among Veterans Administration Cancer Patients With Chemotherapy-Induced Anemia, Shamia Hoque, Brian J. Chen, Martin W. Schoen, Kenneth R. Carson, Jesse Keller, Bartlett J. Witherspoon, Kevin B. Knopf, Y Tony Yang, Benjamin Schooley, Chadi Nabhan, Oliver Sartor, Paul R. Yarnold, Paul Ray, Laura Bobolts, William J. Hrushesky, Michael Dickson, Charles L. Bennett

Open Access Publications

Erythropoisis stimulating agent (ESA) use was addressed in Food and Drug Administration (FDA) Oncology Drug Advisory Committee (ODAC) meetings between 2004 and 2008. FDA safety-focused regulatory actions occurred in 2007 and 2008. In 2007, black box warnings advised of early death and venous thromboembolism (VTE) risks with ESAs in oncology. In 2010, a Risk Evaluation Strategies (REMS) was initiated, with cancer patient consent that mortality and VTE risks were noted with ESAs. We report warnings and REMS impacts on ESA utilization among Veterans Administration (VA) cancer patients with chemotherapy-induced anemia (CIA). Data were from Veterans Affairs database (2003-2012). Epoetin and …