Medicine and Health Sciences Commons^™

Rapid And Sustained Response To Immune Checkpoint Inhibition In Cutaneous Squamous Cell Carcinoma After Allogenic Hematopoietic Cell Transplant For Sézary Syndrome, Karam Khaddour, Amy Musiek, Lynn A Cornelius, Farrokh Dehdashti, Peter Westervelt, Ryan Fields, George Ansstas

2010-2019 OA Pubs

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is not uncommon in association with indolent malignancies that were treated with prior radiotherapy and after allogenic bone marrow transplantation. On the other hand, cutaneous T-cell lymphoma (CTCL) is a subtype of non-Hodgkin's lymphoma which is characterized by an indolent course, with relative refractoriness to conventional chemotherapies and radiotherapy, and occasionally referred for allogeneic hematopoietic cell transplantation (allo-HCT). Recently, the use of immune checkpoint inhibitors has gained attention in the treatment of both cutaneous squamous cell carcinoma and hematological malignancies. However, many patients with hematological malignancies eventually undergo allo-HCT, raising the concern of potential …

Immune Globulin Subcutaneous, Human - Klhw 20% For Primary Humoral Immunodeficiency: An Open-Label, Phase Iii Study, John W Sleasman, William R Lumry, Iftikhar Hussain, H James Wedner, James B Harris, Kecia L Courtney, Elsa Mondou, Jiang Lin, Mark R Stein

2010-2019 OA Pubs

No abstract provided.

Pharmacokinetics Of Once-Daily Extended-Release Tacrolimus Tablets Versus Twice-Daily Capsules In De Novo Liver Transplant, Derek A Dubay, Lewis Teperman, Kimi Ueda, Andrew Silverman, William Chapman, Angel E Alsina, Carmelina Tyler, Daniel R Stevens

2010-2019 OA Pubs

The pharmacokinetics of once-daily extended-release tacrolimus tablets (LCPT) in de novo liver transplantation have not been previously reported. In this phase II, randomized, open-label study, de novo liver transplant recipients were randomized to LCPT 0.07-0.13 mg/kg/day (taken once daily; n = 29) or twice-daily immediate-release tacrolimus capsules (IR-Tac) at 0.10-0.15 mg/kg/day (divided twice daily; n = 29). Subsequent doses of both drugs were adjusted to maintain tacrolimus trough concentrations of 5 to 20 ng/mL through day 90, and 5-15 ng/mL thereafter. Twenty-four-hour pharmacokinetic profiles were obtained on days 1, 7, and 14, with trough concentration and efficacy/safety monitoring through year …

Noninvasive Detection Of Graft Injury After Heart Transplant Using Donor-Derived Cell-Free Dna: A Prospective Multicenter Study, Kiran K Khush, Jignesh Patel, Sean Pinney, Andrew Kao, Rami Alharethi, Eugene Depasquale, Gregory Ewald, Peter Berman, Manreet Kanwar, David Hiller, James P Yee, Robert N Woodward, Shelley Hall, Jon Kobashigawa

2020-Current year OA Pubs

Standardized donor-derived cell-free DNA (dd-cfDNA) testing has been introduced into clinical use to monitor kidney transplant recipients for rejection. This report describes the performance of this dd-cfDNA assay to detect allograft rejection in samples from heart transplant (HT) recipients undergoing surveillance monitoring across the United States. Venous blood was longitudinally sampled from 740 HT recipients from 26 centers and in a single-center cohort of 33 patients at high risk for antibody-mediated rejection (AMR). Plasma dd-cfDNA was quantified by using targeted amplification and sequencing of a single nucleotide polymorphism panel. The dd-cfDNA levels were correlated to paired events of biopsy-based diagnosis …

Sexual Violation Of Patients By Physicians: A Mixed-Methods, Exploratory Analysis Of 101 Cases, James M Dubois, Heidi A Walsh, John T Chibnall, Emily E Anderson, Michelle R Eggers, Mobolaji Fowose, Hannah Ziobrowski

2010-2019 OA Pubs

A mixed-method, exploratory design was used to examine 101 cases of sexual violations in medicine. The study involved content analysis of cases to characterize the physicians, patient-victims, the practice setting, kinds of sexual violations, and consequences to the perpetrator. In each case, a criminal law framework was used to examine how motives, means, and opportunity combined to generate sexual misconduct. Finally, cross-case analysis was performed to identify clusters of causal factors that explain specific kinds of sexual misconduct. Most cases involved a combination of five factors: male physicians (100%), older than the age of 39 (92%), who were not board …

Neoadjuvant Folfirinox In Patients With Borderline Resectable Pancreatic Cancer: A Systematic Review And Patient-Level Meta-Analysis, Quisette P Janssen, Andrea Wang-Gillam, Et Al.

2010-2019 OA Pubs

BACKGROUND: FOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer (BRPC) remains debated.

METHODS: We performed a systematic review and patient-level meta-analysis on neoadjuvant FOLFIRINOX in patients with BRPC. Studies with BRPC patients who received FOLFIRINOX as first-line neoadjuvant treatment were included. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival, resection rate, R0 resection rate, and grade III-IV adverse events. Patient-level survival outcomes were obtained from authors of the included studies and analyzed using the Kaplan-Meier method.

RESULTS: We included 24 studies …

White Matter Damage, Neuroinflammation, And Neuronal Integrity In Hand, Aljoharah Alakkas, David B Clifford, Et Al.

2010-2019 OA Pubs

HIV-associated neurocognitive disorders (HANDs) persist even with virologic suppression on combination antiretroviral therapy (cART), and the underlying pathophysiological mechanisms are not well understood. We performed structural magnetic resonance imaging and MR spectroscopy (MRS) in HIV+ individuals without major neurocognitive comorbidities. Study participants were classified as neurocognitively unimpaired (NU), asymptomatic (ANI), mild neurocognitive disorder (MND), or HIV-associated dementia (HAD). Using structural MRI, we measured volumes of cortical and subcortical gray matter and total and abnormal white matter (aWM). Using single-voxel MRS, we estimated metabolites in frontal gray matter (FGM) and frontal white matter (FWM) and basal ganglia (BG) regions. Adjusted odds …

Association Between Reductions Of Number Of Cigarettes Smoked Per Day And Mortality Among Older Adults In The United States, Maki Inoue-Choi, Patricia Hartge, Yikyung Park, Christian C Abnet, Neal D Freedman

2010-2019 OA Pubs

Many smokers do not quit but instead reduce the number of cigarettes they smoke per day (CPD) over their lifetime. Yet the associations of such changes in CPD with health risks are unclear. We examined the association of changes in CPD with subsequent death in the period 2004-2011 among 253,947 participants of the National Institutes of Health-AARP Diet and Health Study. Using a questionnaire assessing responders' history of smoking cigarettes, we identified cigarette smokers who quit, decreased, maintained, or increased their CPD between ages 25-29 and 50-59 years. Hazard ratios and 95% confidence intervals were obtained from multivariable adjusted Cox …

Developing And Assessing The Feasibility Of A Home-Based Preexposure Prophylaxis Monitoring And Support Program, Aaron J Siegler, Kenneth H Mayer, Albert Y Liu, Rupa R Patel, Lauren M Ahlschlager, Colleen S Kraft, Rossi Fish, Sarah E Wiatrek, Patrick S Sullivan

2010-2019 OA Pubs

We piloted PrEP@Home, a preexposure prophylaxis system of remote laboratory and behavioral monitoring designed to replace routine quarterly follow-up visits with home care to reduce the patient and provider burden. The system was highly acceptable and in-demand for future use, and more than one-third of participants reported greater likelihood of persisting in care if available.

Understanding The Association Between Negative Symptoms And Performance On Effort-Based Decision-Making Tasks: The Importance Of Defeatist Performance Beliefs, L Felice Reddy, William P Horan, Deanna M Barch, Robert W Buchanan, James M Gold, Stephen R Marder, Jonathan K Wynn, Jared Young, Michael F Green

2010-2019 OA Pubs

Effort-based decision-making paradigms are increasingly utilized to gain insight into the nature of motivation deficits. Research has shown associations between effort-based decision making and experiential negative symptoms; however, the associations are not consistent. The current study had two primary goals. First, we aimed to replicate previous findings of a deficit in effort-based decision making among individuals with schizophrenia on a test of cognitive effort. Second, in a large sample combined from the current and a previous study, we sought to examine the association between negative symptoms and effort by including the related construct of defeatist beliefs. The results replicated previous …

White Matter Diffusion Alterations Precede Symptom Onset In Autosomal Dominant Alzheimer's Disease, Miguel Ángel Araque Caballero, Tammie Benzinger, Anne M Fagan, Randall J Bateman, Celeste Karch, John C Morris, Jason Hassenstab, Et Al.

2010-2019 OA Pubs

White matter alterations are present in the majority of patients with Alzheimer's disease type dementia. However, the spatiotemporal pattern of white matter changes preceding dementia symptoms in Alzheimer's disease remains unclear, largely due to the inherent diagnostic uncertainty in the preclinical phase and increased risk of confounding age-related vascular disease and stroke in late-onset Alzheimer's disease. In early-onset autosomal-dominantly inherited Alzheimer's disease, participants are destined to develop dementia, which provides the opportunity to assess brain changes years before the onset of symptoms, and in the absence of ageing-related vascular disease. Here, we assessed mean diffusivity alterations in the white matter …

Randomized, Double-Blind, Phase Ii Study Of Temozolomide In Combination With Either Veliparib Or Placebo In Patients With Relapsed-Sensitive Or Refractory Small-Cell Lung Cancer, M Catherine Pietanza, Saiama N Waqar, Et Al

2010-2019 OA Pubs

Purpose Both temozolomide (TMZ) and poly (ADP-ribose) polymerase (PARP) inhibitors are active in small-cell lung cancer (SCLC). This phase II, randomized, double-blind study evaluated whether addition of the PARP inhibitor veliparib to TMZ improves 4-month progression-free survival (PFS). Patients and Methods A total of 104 patients with recurrent SCLC were randomly assigned 1:1 to oral veliparib or placebo 40 mg twice daily, days 1 to 7, and oral TMZ 150 to 200 mg/m

Transcription Factor Gata4 Associates With Mesenchymal-Like Gene Expression In Human Hepatoblastoma Cells, Tea Soini, Katja Eloranta, Marjut Pihlajoki, Antti Kyrönlahti, Oyediran Akinrinade, Noora Andersson, Jouko Lohi, Mikko P Pakarinen, David B Wilson, Markku Heikinheimo

2010-2019 OA Pubs

GATA4, a transcription factor crucial for early liver development, has been implicated in the pathophysiology of hepatoblastoma, an embryonal tumor of childhood. However, the molecular and phenotypic consequences of GATA4 expression in hepatoblastoma are not fully understood. We surveyed GATA4 expression in 24 hepatoblastomas using RNA in situ hybridization and immunohistochemistry. RNA interference was used to inhibit GATA4 in human HUH6 hepatoblastoma cells, and changes in cell migration were measured with wound healing and transwell assays. RNA microarray hybridization was performed on control and GATA4 knockdown HUH6 cells, and differentially expressed genes were validated by quantitative polymerase chain reaction or …

Left Frontal Hub Connectivity Delays Cognitive Impairment In Autosomal-Dominant And Sporadic Alzheimer's Disease, Nicolai Franzmeier, Anne M Fagan, Katrina Paumier, Tammie Benzinger, John C Morris, Randall J Bateman, Et Al.

2010-2019 OA Pubs

Patients with Alzheimer's disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer's pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer's disease. However, no study has yet assessed whether such hub connectivity of the left …

Prevalence, Incidence, And Clearance Of Anal High-Risk Human Papillomavirus Infection Among Hiv-Infected Men In The Sun Study, Pragna Patel, Tim Bush, Erna Milunka Kojic, Lois Conley, Elizabeth R Unger, Teresa M Darragh, Keith Henry, John Hammer, Gerome Escota, Joel M Palefsky, John T Brooks

2010-2019 OA Pubs

BACKGROUND: The natural history of anal human papilloma virus (HPV) infection among human immunodeficiency virus (HIV)-infected men is unknown.

METHODS: Annually, from 2004 to 2012, we examined baseline prevalence, incidence, and clearance of anal HPV infection at 48 months, and associated factors among HIV-infected men.

RESULTS: We examined 403 men who have sex with men (MSM) and 96 men who have sex with women (MSW) (median age 42 years for both, 78% versus 81% prescribed cART, median CD4+ T-lymphocyte cell count 454 versus 379 cells/mm3, and 74% versus 75% had undetectable viral load, respectively). Type 16 prevalence among MSM and …

Insights Into Onchocerca Volvulus Population Biology Through Multilocus Immunophenotyping, Carmelle T Norice-Tra, José Ribeiro, Sasisekhar Bennuru, Michael P Fay, Rahul Tyagi, Makedonka Mitreva, Thomas B Nutman

2010-2019 OA Pubs

We have developed a serologically based immunophenotyping approach to study Onchocerca volvulus (Ov) population diversity. Using genomic sequence data and polymerase chain reaction-based genotyping, we identified nonsynonymous single-nucleotide polymorphisms (SNPs) in the genes of 16 major immunogenic Ov proteins: Ov-CHI-1/Ov-CHI-2, Ov16, Ov-FAR-1, Ov-CPI-1, Ov-B20, Ov-ASP-1, Ov-TMY-1, OvSOD1, OvGST1, Ov-CAL-1, M3/M4, Ov-RAL-1, Ov-RAL-2, Ov-ALT-1, Ov-FBA-1, and Ov-B8. We assessed the immunoreactivity of onchocerciasis patient sera (n = 152) from the Americas, West Africa, Central Africa, and East Africa against peptides derived from 10 of these proteins containing SNPs. Statistically significant variation in immunoreactivity among the regions was seen in SNP-containing peptides …

Subcutaneous Peginterferon Β-1a Injection-Site Reaction Experience And Mitigation: Delphi Analysis Of The Allow Study, Barry Hendin, Deren Huang, Sibyl Wray, Robert T Naismith, Sheri Rosenblatt, Javier Zambrano, Brian Werneburg

2010-2019 OA Pubs

AIM: The objective of this Delphi analysis was to obtain consensus on injection-site reaction (ISR) experience and mitigation strategies for patients with relapsing-remitting multiple sclerosis switching from nonpegylated interferons (IFNs) to peginterferon β-1a in the ALLOW Phase IIIb trial using a three-step approach.

METHODS: Study investigators and coordinators from investigative sites enrolling four or more patients in ALLOW participated in three rounds of questionnaires and interviews.

RESULTS: Respondents (n = 37) agreed that the most common ISR, erythema, was not disruptive to daily activities. Patient education, as a conversation with a clinician about ISR potential, was recommended.

CONCLUSION: The consensus …