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Katelyn Paz, Ryan Flynn, Jing Du, Stacey Tannheimer, Amy J Johnson, Shuai Dong, Anne-Katrien Stark, Klaus Okkenhaug, Angela Panoskaltsis-Mortari, Peter T Sage, Arlene H Sharpe, Leo Luznik, Jerome Ritz, Robert J Soiffer, Corey S Cutler, John Koreth, Joseph H Antin, David B Miklos, Kelli P MacDonald, Geoffrey R Hill, Ivan Maillard, Jonathan S Serody, William J Murphy, David H Munn, Colby Feser, Michael Zaiken, Bart Vanhaesebroeck, Laurence A Turka, John C Byrd, Bruce R Blazar
Chronic graft-versus-host disease is a leading cause of morbidity and mortality following allotransplant. Activated donor effector T-cells can differentiate into pathogenic T helper (Th)-17 cells and germinal center -promoting Tfollicular helper cells, resulting in cGVHD. Phosphoinositide-3-kinase-δ, a lipid kinase, is critical for activated T-cell survival, proliferation, differentiation, and metabolism. We demonstrate PI3Kδ activity in donor T-cells that become Tfhs is required for cGVHD in a non-sclerodermatous multi-organ system disease model that includes bronchiolitis obliterans, dependent upon GC B-cells, Tfhs, and counterbalanced by Tfollicular regulatory cells, each requiring PI3Kδ signaling for function and survival...
February 12, 2019: American Journal of Transplantation
Sarah Melville, James Brian Byrd
PURPOSE OF REVIEW: The purpose of this review is to discuss the implications of personalized medicine for the treatment of hypertension, including resistant hypertension. RECENT FINDINGS: We suggest a framework for the personalized treatment of hypertension based on the concept of a trade-off between simplicity and personalization. This framework is based on treatment strategies classified as low, medium, or high information burden personalization approaches. The extent to which a higher information burden is justified depends on the clinical scenario, particularly the ease with which the blood pressure can be controlled...
February 12, 2019: Current Hypertension Reports
Kaitlyn M Eck, Colleen L Delaney, Melissa D Olfert, Karla P Shelnutt, Carol Byrd-Bredbenner
Objective: Obesity is a public health concern for children and adults and effective obesity prevention programming is needed urgently. The effectiveness of health-related messaging and interventions is influenced by the way content is framed. HomeStyles is an obesity prevention program, which aims to promote health through the frame of improved quality of life. Methods: Thus, focus groups were conducted with English- and Spanish-speaking parents of school-aged children (ages 6-11) to identify key quality-of-life determinants as described by parents...
2019: SAGE Open Medicine
Chao Gao, Melinda S Hanes, Lauren A Byrd-Leotis, Mohui Wei, Nan Jia, Robert J Kardish, Tanya R McKitrick, David A Steinhauer, Richard D Cummings
The glycan ligands recognized by Siglecs, influenza viruses, and galectins, as well as many plant lectins, are not well defined. To explore their binding to asparagine (Asn)-linked N-glycans, we synthesized a library of isomeric multiantennary N-glycans that vary in terminal non-reducing sialic acid, galactose, and N-acetylglucosamine residues, as well as core fucose. We identified specific recognition of N-glycans by several plant lectins, human galectins, influenza viruses, and Siglecs, and explored the influence of sialic acid linkages and branching of the N-glycans...
January 22, 2019: Cell Chemical Biology
Krzysztof Mrózek, Ann-Kathrin Eisfeld, Jessica Kohlschmidt, Andrew J Carroll, Christopher J Walker, Deedra Nicolet, James S Blachly, Marius Bill, Dimitrios Papaioannou, Eunice S Wang, Geoffrey L Uy, Jonathan E Kolitz, Bayard L Powell, William Blum, Richard M Stone, John C Byrd, Clara D Bloomfield
Complex karyotype (CK) with ≥ 3 abnormalities is detected in 10-12% of patients with acute myeloid leukemia (AML) and associated with poor prognosis. The most common unbalanced abnormalities found in CK result in loss of material from the 5q, 7q, and/or 17p chromosome arms. The presence of 5q, 7q, and/or 17p abnormalities denotes typical CK and their absence denotes atypical CK. Since molecular features of CK-AML are not well characterized, we investigated mutational status of 81 leukemia/cancer-associated genes in 160 clinically well-characterized patients...
February 8, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Emily M McWilliams, Christopher R Lucas, Timothy Chen, Bonnie K Harrington, Ronni Wasmuth, Amanda Campbell, Kerry A Rogers, Carolyn M Cheney, Xiaokui Mo, Leslie A Andritsos, Farrukh T Awan, Jennifer Woyach, William E Carson, Jonathan Butchar, Susheela Tridandapani, Erin Hertlein, Carlos E Castro, Natarajan Muthusamy, John C Byrd
The Bruton tyrosine kinase inhibitor (BTKi) ibrutinib has transformed chronic lymphocytic leukemia (CLL) therapy but requires continuous administration. These factors have spurred interest in combination treatments. Unlike with chemotherapy, CD20-directed antibody therapy has not improved the outcome of BTKi treatment. Whereas CD20 antigen density on CLL cells decreases during ibrutinib treatment, the B-cell activating factor (BAFF) and its receptor (BAFF-R) remain elevated. Furthermore, BAFF signaling via noncanonical NF-κB remains elevated with BTKi treatment...
February 12, 2019: Blood Advances
Yifei Li, Olivier Soubias, Jess Li, Shangjin Sun, Paul A Randazzo, R Andrew Byrd
Lipidated small GTP-binding proteins of the Arf family interact with multiple cellular partners and with membranes to regulate intracellular traffic and organelle structure. Here, we focus on the ADP-ribosylation factor 1 (Arf1), which interacts with numerous proteins in the Arf pathway, such as the ArfGAP ASAP1 that is highly expressed and activated in several cancer cell lines and associated with enhanced migration, invasiveness, and poor prognosis. Understanding the molecular and mechanistic details of Arf1 regulation at the membrane via structural and biophysical studies requires large quantities of fully functional protein bound to lipid bilayers...
February 8, 2019: Biochemistry
Jiayun Fang, Amanda Kornfield, Alex Clavijo, Shikhar Vyas, Alison Ulbrandt, Carsten Schroeder, J Kenneth Byrd, Daniel Kleven
Myoepithelial carcinoma is an uncommon tumor of the salivary glands, most commonly the parotid gland. Clear cell myoepithelial carcinoma is a rare variant with an aggressive behavior. Here, we describe a case of clear cell myoepithelial carcinoma arising from the hard palate in an elderly male who underwent resection of the tumor and postop radiation. Posttreatment imaging demonstrated bilateral pulmonary nodules and a C2 body lesion concerning for metastasis. Biopsy of the lung lesions revealed a monomorphous population of optically clear cells with hyperchromatic and pleomorphic nuclei which were morphologically similar to the prior resection specimen...
2019: Case Reports in Pathology
Victoria Byrd, Attila Nemeth
Epidermolysis bullosa acquisita is a rare autoimmune bullous disease involving the skin and mucosa, most commonly treated with systemic corticosteroids. This case illustrates the importance of counseling patients on medication side effects and ensuring close physician follow-up during an extended course of steroids. A 46-year-old man presented to the emergency department with weakness, fatigue, dizziness and polyuria in the setting of eight weeks of prednisone therapy for a flare-up of his bullous disease...
November 19, 2018: Curēus
Shaneice R Mitchell, Karilyn Larkin, Nicole R Grieselhuber, Tzung-Huei Lai, Matthew Cannon, Shelley Orwick, Pratibha Sharma, Yerdanose Asemelash, Pu Zhang, Virginia M Goettl, Larry Beaver, Alice Mims, Vinay K Puduvalli, James S Blachly, Amy Lehman, Bonnie Harrington, Sally Henderson, Justin T Breitbach, Katie E Williams, Shuai Dong, Erkan Baloglu, William Senapedis, Karl Kirschner, Deepa Sampath, Rosa Lapalombella, John C Byrd
Treatment options for acute myeloid leukemia (AML) remain extremely limited and associated with significant toxicity. Nicotinamide phosphoribosyltransferase (NAMPT) is involved in the generation of NAD+ and a potential therapeutic target in AML. We evaluated the effect of KPT-9274, a p21-activated kinase 4/NAMPT inhibitor that possesses a unique NAMPT-binding profile based on in silico modeling compared with earlier compounds pursued against this target. KPT-9274 elicited loss of mitochondrial respiration and glycolysis and induced apoptosis in AML subtypes independent of mutations and genomic abnormalities...
February 12, 2019: Blood Advances
Nikki Clauss, Jennifer Byrd-Craven
Literature suggests that stress-induced consumption of highly palatable food is a behavior pertaining almost exclusively to women. Given the overall association between stress levels and obesity in the United States transcends sex, it seems likely that males also engage in stress-induced consumption of highly palatable food in certain contexts. In the current study, 168 males and females (54.2% female) were randomly assigned to one of three experimental groups: achievement stress, social rejection stress, and a control condition...
January 23, 2019: Physiology & Behavior
Jim H Hughes, Mitch A Phelps, Richard N Upton, Stephanie E Reuter, Yue Gao, John C Byrd, Michael R Grever, Craig C Hofmeister, Guido Marcucci, William Blum, Kristie A Blum, David J R Foster
AIMS: Lenalidomide is an immunomodulatory imide drug (IMiD) used broadly in the treatment of multiple myeloma and lymphoma. It continues to be evaluated in chronic lymphocytic leukaemia (CLL) at lower doses due to dose-related toxicities including tumour flare and tumour lysis syndrome. This study aimed to develop a population pharmacokinetic model for lenalidomide in multiple cancers, including CLL, to identify any disease-related differences in disposition. METHODS: Lenalidomide concentrations from four clinical trials were collated (1999 samples, 125 subjects), covering four cancers (multiple myeloma, CLL, acute myeloid leukaemia and acute lymphoblastic leukaemia) and a large dose range (2...
January 22, 2019: British Journal of Clinical Pharmacology
Sompop Bencharit, Thiago Morelli, Silvana Barros, Jackson Seagroves, Steven Kim, Ning Yu, Kevin Byrd, Christian Brenes, Steven Offenbacher
Porous tantalum trabecular metal (PTTM) has long been used in orthopedics to enhance neovascularization, wound healing, and osteogenesis; recently it has been incorporated into titanium alloy dental implants. However, little is known about the biological responses to PTTM in the human oral cavity. We hypothesized that, compared to conventional titanium alloy; PTTM had greater expression of genes specific to neovascularization, wound healing, and osteogenesis during the initial healing period. Twelve subjects required at least four implants in the mandible were enrolled...
January 21, 2019: Journal of Oral Implantology
William G Wierda, John C Byrd, Jeremy S Abramson, Syed F Bilgrami, Greg Bociek, Danielle Brander, Jennifer Brown, Asher A Chanan-Khan, Julio C Chavez, Steve E Coutre, Randall S Davis, Christopher D Fletcher, Brian Hill, Brad S Kahl, Manali Kamdar, Lawrence D Kaplan, Nadia Khan, Thomas J Kipps, Shuo Ma, Sami Malek, Anthony Mato, Claudio Mosse, Vishala T Neppalli, Mazyar Shadman, Tanya Siddiqi, Deborah Stephens, Nina Wagner, Mary A Dwyer, Hema Sundar
Chronic lymphocytic leukemia (CLL) is generally characterized by an indolent disease course. Histologic transformation (also known as Richter's transformation) to more aggressive lymphomas, such as diffuse large B-cell lymphoma or Hodgkin lymphoma, occurs in approximately 2% to 10% of patients and is associated with a poor prognosis. These NCCN Guidelines Insights discuss the recommendations for the diagnosis and management of patients with histologic transformation.
January 2019: Journal of the National Comprehensive Cancer Network: JNCCN
Lyndsey Runaas, Flora Hoodin, Anna Munaco, Alex Fauer, Roshun Sankaran, Tracey Churay, Saara Mohammed, Sajjad Seyedsalehi, Grant Chappell, Noelle Carlozzi, Michael D Fetters, Rachel Kentor, Leah McDiarmid, Kristina Brookshire, Casiana Warfield, Michelle Byrd, Sharon Kaziunas, Molly Maher, John Magenau, Larry An, Amy Cohn, David A Hanauer, Sung Won Choi
PURPOSE: Health information technology (IT) is an ideal medium to improve the delivery of patient-centered care and increase patient engagement. Health IT interventions should be designed with the end user in mind and be specific to the needs of a given population. Hematopoietic cell transplantation (HCT), commonly referred to as blood and marrow transplantation (BMT), is a prime example of a complex medical procedure where patient-caregiver-provider engagement is central to a safe and successful outcome...
December 2018: JCO Clinical Cancer Informatics
Kathy K Byrd, Felicia Hardnett, Patrick G Clay, Ambrose Delpino, Ron Hazen, Michael D Shankle, Nasima M Camp, Sumihiro Suzuki, Paul J Weidle
Poor retention in HIV care is associated with higher morbidity and mortality and greater risk of HIV transmission. The Patient-Centered HIV Care Model (PCHCM) integrated community-based pharmacists with medical providers. The model required sharing of patient clinical information and collaborative therapy-related action planning. The proportion of persons retained in care (≥1 medical visit in each 6-month period of a 12-month measurement period with ≥60 days between visits), pre- and post-PCHCM implementation, was modeled using log binomial regression...
January 16, 2019: AIDS Patient Care and STDs
Ashley Palvic, Dana Liu, Kara Baker, Joseph House, Michael Byrd, Tina Martinek, Diana O'Leary, Sally A Santen
Introduction: Feedback provides valuable input for improving physician performance. Conventionally, feedback is obtained from attending physicians; however, residents work in close contact with other members of the care team, especially nurses. Nurses may have more opportunity to directly observe trainees. In addition, they may value different behaviors and provide unique feedback. The objective of this study was to examine the nurse's perspective of resident performance in the emergency department...
January 2019: Western Journal of Emergency Medicine
Deborah M Stephens, John C Byrd
Chronic lymphocytic leukemia (CLL) therapy has changed dramatically with the introduction of several targeted therapeutics. Ibrutinib was the first approved for use in 2014 and now is used for initial and salvage therapy of CLL patients. With its widespread use in clinical practice, ibrutinib's common and uncommon adverse events reported less frequently in earlier clinical trials have been experienced more frequently in real-world practice. In particular, atrial fibrillation, bleeding, infections, and arthralgias have been reported...
January 14, 2019: Blood
Aykut A Unsal, J Renee Booth, Nicholas A Rossi, J Kenneth Byrd, Stilianos E Kountakis
OBJECTIVES: Basaloid nasopharyngeal carcinoma (BNPC) is an extremely rare malignancy with a paucity of cases reported in the literature. This analysis represents the largest cohort of BNPC to date. STUDY DESIGN: Retrospective population-based analysis. METHODS: The Surveillance, Epidemiology, and End Results registry from 2001 to 2015 was utilized to extract a total of 82 cases of BNPC. Data were analyzed for incidence trends, demographic, and tumor characteristics, as well as potential outcome prognosticators...
January 10, 2019: Laryngoscope
Christine P Stewart, Kathryn G Dewey, Audrie Lin, Amy J Pickering, Kendra A Byrd, Kaniz Jannat, Shahjahan Ali, Gouthami Rao, Holly N Dentz, Marion Kiprotich, Charles D Arnold, Benjamin F Arnold, Lindsay H Allen, Setareh Shahab-Ferdows, Ayse Ercumen, Jessica A Grembi, Abu Mohd Naser, Mahbubur Rahman, Leanne Unicomb, John M Colford, Stephen P Luby, Clair Null
Background: Anemia in young children is a global health problem. Risk factors include poor nutrient intake and poor water quality, sanitation, or hygiene. Objective: We evaluated the effects of water quality, sanitation, handwashing, and nutrition interventions on micronutrient status and anemia among children in rural Kenya and Bangladesh. Design: We nested substudies within 2 cluster-randomized controlled trials enrolling pregnant women and following their children for 2 y...
January 1, 2019: American Journal of Clinical Nutrition
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