Medicine and Health Sciences Commons^™

Point-Of-Care Lung Ultrasound For Covid-19: Findings And Prognostic Implications From 105 Consecutive Patients, Kosuke Yasukawa, Taro Minami, David R Boulware, Ayako Shimada, Ernest A Fischer

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Background: The prognostic value of point-of-care lung ultrasound has not been evaluated in a large cohort of patients with COVID-19 admitted to general medicine ward in the United States. The aim of this study was to describe lung ultrasound findings and their prognostic value in patients with COVID-19 admitted to internal medicine ward.

Method: This prospective observational study consecutively enrolled 105 hospitalized participants with COVID-19 at 2 tertiary care centers. Ultrasound was performed in 12 lung zones within 24 hours of admission. Findings were assessed relative to 4 outcomes: intensive care unit (ICU) need, need for intensive respiratory support, length …

Epidemiology Of Covid-19 And Predictors Of Outcome In Nigeria: A Single-Center Study., Olayinka Rasheed Ibrahim, Bello Muhammed Suleiman, Suleiman Bello Abdullahi, Taofeek Oloyede, Abdallah Sanda, Maruf Sanusi Gbadamosi, Bashir Olajide Yusuf, Rabilu Yandoma Iliyasu, Lawal Magaji Ibrahim, Adamu Danladi Dawud, Sulaiman Saidu Bashir, Nwawueze Efam Okonta, Wasinda Francis Umar, Abiodun Gbenga Tekobo, Muhammadu Sani Abubakar, Bashir Taiye Aminu, Shuaibu Onoruoyiza Ibrahim, Rasaq Olaosebikan, Olugbenga Ayodeji Mokuolu

Department of Pharmacology and Experimental Therapeutics Faculty Papers

There is a paucity of information regarding the epidemiology and outcome of COVID-19 from low/middle-income countries, including from Nigeria. This single-center study described the clinical features, laboratory findings, and predictors of in-hospital mortality of COVID-19 patients. Patients admitted between April 10, 2020 and June 10, 2020 were included. Forty-five patients with a mean age of 43 (16) years, predominantly male (87%), presented with fever (38%), cough (29%), or dyspnea (24%). In-hospital mortality was 16%. The independent predictors of mortality were hypoxemia (adjusted odds ratio [aOR]: 2.5; 95% CI: 1.3-5.1) and creatinine > 1.5 mg/dL (aOR: 4.3; 95% CI: 1.9-9.8).

Simulation-Based Mastery Learning Compared To Standard Education For Discussing Diagnostic Uncertainty With Patients In The Emergency Department: A Randomized Controlled Trial., Danielle M. Mccarthy, Rhea E. Powell, Kenzie A. Cameron, David H. Salzman, Dimitrios Papanagnou, Amanda Doty, Benjamin E. Leiby, Katherine Piserchia, Matthew R. Klein, Xiao C. Zhang, William C. Mcgaghie, Kristin L. Rising

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Diagnostic uncertainty occurs frequently in emergency medical care, with more than one-third of patients leaving the emergency department (ED) without a clear diagnosis. Despite this frequency, ED providers are not adequately trained on how to discuss diagnostic uncertainty with these patients, who often leave the ED confused and concerned. To address this training need, we developed the Uncertainty Communication Education Module (UCEM) to teach physicians how to discuss diagnostic uncertainty. The purpose of the study is to evaluate the effectiveness of the UCEM in improving physician communications.

METHODS: The trial is a multicenter, two-arm randomized controlled trial designed to …

Role Of A Plausible Nuisance Contributor In The Declining Obesity-Mortality Risks Over Time., Tapan Mehta, Nicholas M. Pajewski, Scott W. Keith, Kevin Fontaine, David B. Allison

Department of Pharmacology and Experimental Therapeutics Faculty Papers

CONTEXT: Recent analyses of epidemiological data including the National Health and Nutrition Examination Survey (NHANES) have suggested that the harmful effects of obesity may have decreased over calendar time. The shifting BMI distribution over time coupled with the application of fixed broad BMI categories in these analyses could be a plausible "nuisance contributor" to this observed change in the obesity-associated mortality over calendar time.

OBJECTIVE: To evaluate the extent to which observed temporal changes in the obesity-mortality association may be due to a shifting population distribution for body mass index (BMI), coupled with analyses based on static, broad BMI categories. …

Gm1 Ganglioside In Parkinson's Disease: Pilot Study Of Effects On Dopamine Transporter Binding., Jay S. Schneider, Franca Cambi, Stephen M. Gollomp, Hiroto Kuwabara, James R. Brašić, Benjamin E. Leiby, Stephanie Sendek, Dean F. Wong

Department of Pharmacology and Experimental Therapeutics Faculty Papers

OBJECTIVE: GM1 ganglioside has been suggested as a treatment for Parkinson's disease (PD), potentially having symptomatic and disease modifying effects. The current pilot imaging study was performed to examine effects of GM1 on dopamine transporter binding, as a surrogate measure of disease progression, studied longitudinally.

METHODS: Positron emission tomography (PET) imaging data were obtained from a subset of subjects enrolled in a delayed start clinical trial of GM1 in PD [1]: 15 Early-start (ES) subjects, 14 Delayed-start (DS) subjects, and 11 Comparison (standard-of-care) subjects. Treatment subjects were studied over a 2.5 year period while Comparison subjects were studied over 2 …

Adolescent And Adult African Americans Have Similar Metabolic Dyslipidemia., Samuel S. Gidding, Scott W. Keith, Bonita Falkner

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: African Americans (AAs) have lower triglyceride (TG) and higher high-density lipoprotein cholesterol (HDL-C) than other ethnic groups; yet, they also have higher risk for developing diabetes mellitus despite the strong relationship of dyslipidemia with insulin resistance. No studies directly compare adolescents and adults with regard to relationships among dyslipidemia, high-sensitivity C-reactive protein (hs-CRP), and insulin resistance. Here, we compare AA adolescents to adults with regard to the relationships of adiposity-related lipid risk markers (TG-to-HDL ratio and non-HDL-C) with body mass index (BMI), waist circumference (WC), homeostasis model of insulin resistance (HOMA), and hs-CRP.

METHODS: Two cohorts of healthy AA …

Analytic Lymph Node Number Establishes Staging Accuracy By Occult Tumor Burden In Colorectal Cancer., Terry Hyslop, David S. Weinberg, Stephanie Schulz, Alan Barkun, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND AND OBJECTIVES: Recurrence in lymph node-negative (pN0) colorectal cancer suggests the presence of undetected occult metastases. Occult tumor burden in nodes estimated by GUCY2C RT-qPCR predicts risk of disease recurrence. This study explored the impact of the number of nodes analyzed by RT-qPCR (analytic) on the prognostic utility of occult tumor burden.

METHODS: Lymph nodes (range: 2-159) from 282 prospectively enrolled pN0 colorectal cancer patients, followed for a median of 24 months (range: 2-63), were analyzed by GUCY2C RT-qPCR. Prognostic risk categorization defined using occult tumor burden was the primary outcome measure. Association of prognostic variables and risk category …

The Incidence Of Deep Vein Thrombosis Detected By Routine Surveillance Ultrasound In Neurosurgery Patients Receiving Dual Modality Prophylaxis., Patricia C Henwood, Thomas M Kennedy, Lynda Thomson, Taki Galanis, George L Tzanis, Geno J Merli, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The optimal method of thromboprophylaxis and the value of screening ultrasonography for detection of deep venous thrombosis (DVT) in neurosurgery patients remains unclear. The goal of this study was to determine the incidence of DVT in neurosurgical patients who, by hospital protocol, receive surveillance ultrasonography of the lower extremities twice weekly, in addition to prophylaxis with unfractionated heparin and external pneumatic compression sleeves. A retrospective review of 7,298 ultrasound studies carried out on 2,593 patients over 4 years at a university neurosurgical hospital was conducted. There was a 7.4% incidence of proximal lower extremity DVT and a 9.7% total incidence …

Association Of Gucy2c Expression In Lymph Nodes With Time To Recurrence And Disease-Free Survival In Pn0 Colorectal Cancer., Scott A Waldman, Terry Hyslop, Stephanie Schulz, Alan Barkun, Karl Nielsen, Janis Haaf, Christine Bonaccorso, Yanyan Li, David S Weinberg

Department of Pharmacology and Experimental Therapeutics Faculty Papers

CONTEXT: The established relationship between lymph node metastasis and prognosis in colorectal cancer suggests that recurrence in 25% of patients with lymph nodes free of tumor cells by histopathology (pN0) reflects the presence of occult metastases. Guanylyl cyclase 2C (GUCY2C) is a marker expressed by colorectal tumors that could reveal occult metastases in lymph nodes and better estimate recurrence risk.

OBJECTIVE: To examine the association of occult lymph node metastases detected by quantifying GUCY2C messenger RNA, using the reverse transcriptase-polymerase chain reaction, with recurrence and survival in patients with colorectal cancer.

DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 257 patients …

A Glycosylated Recombinant Human Granulocyte Colony Stimulating Factor Produced In A Novel Protein Production System (Avi-014) In Healthy Subjects: A First-In Human, Single Dose, Controlled Study., Roslyn Varki, Ed Pequignot, Mark C Leavitt, Andres Ferber, Walter K Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: AVI-014 is an egg white-derived, recombinant, human granulocyte colony-stimulating factor (G-CSF). This healthy volunteer study is the first human investigation of AVI-014. METHODS: 24 male and female subjects received a single subcutaneous injection of AVI-014 at 4 or 8 mcg/kg. 16 control subjects received 4 or 8 mcg/kg of filgrastim (Neupogen, Amgen) in a partially blinded, parallel fashion. RESULTS: The Geometric Mean Ratio (GMR) (90% CI) of 4 mcg/kg AVI-014/filgrastim AUC(0-72 hr) was 1.00 (0.76, 1.31) and Cmax was 0.86 (0.66, 1.13). At the 8 mcg/kg dose, the AUC(0-72) GMR was 0.89 (0.69, 1.14) and Cmax was 0.76 (0.58, …

Overexpression Of Matrix Metalloproteinase 9 In Tumor Epithelial Cells Correlates With Colorectal Cancer Metastasis., David S Zuzga, Ahmara Vivian Gibbons, Peng Li, Wilhelm Johannes Lubbe, Inna Chervoneva, Giovanni Mario Pitari

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Colorectal cancer mortality largely reflects metastasis, the spread of the disease to distant organs. Matrix metalloproteinase 9 (MMP-9) is a key regulator of metastasis and a target for anticancer strategies in colon cancer. Here, the overexpression of MMP-9 in pure tumor epithelial, but nor stromal, cell populations was associated with metastatic progression of colorectal cancer, as defined by reverse transcriptase-polymerase chain reaction (qRT-PCR) and confirmed by immunostaining. Thus, cancer cell MMP-9 represents a novel, selective prognostic and predictive factor that may be exploited for more effective disease stage stratification and therapeutic regimen selection in patients with colorectal cancer.

Transgenic Avian-Derived Recombinant Human Interferon-Alpha2b (Avi-005) In Healthy Subjects: An Open-Label, Single-Dose, Controlled Study., T B Patel, E Pequignot, S H Parker, M C Leavitt, H E Greenberg, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND/AIMS: This study characterized the safety and pharmacological properties of AVI-005, a novel glycosylated recombinant human interferon-alpha2b produced from the egg whites of chickens transfected with human cDNA.

METHODS: 18 healthy volunteers received single subcutaneous rising doses (0.5, 1.66 or 5 million international units, MIU) of AVI-005. A randomized parallel comparator group of 10 subjects received 5 MIU of unglycosylated IFN-alpha2b (Intron A). The pharmacokinetic parameters t1/2, tmax, Cmax, AUC0-24h, Vd, and clearance were compared between AVI-005 and unglycosylated IFN-alpa2b.

RESULTS: At equipotent doses, AVI-005 had a larger AUC0-24h than the control interferon. Pharmacodynamic markers ofneopterin and beta2-microglobulin for the …