Medicine and Health Sciences Commons^™

National Trends In Admission And In-Hospital Mortality Of Patients With Heart Failure In The United States (2001–2014), Emmanuel Akintoye, Alexandros Briasoulis, Alexander Egbe, Shannon M. Dunlay, Sudhir Kushwaha, Diane Levine, Luis Afonso, Dariush Mozaffarian, Jarrett Weinberger

Internal Medicine Faculty Publications

Background-—To investigate heart failure (HF) hospitalization trends in the United States and change in trends after publication of management guidelines.

Methods and Results-—Using data from the National Inpatient Sample and the US Census Bureau, annual national estimates in HF admissions and in-hospital mortality were estimated for years 2001 to 2014, during which an estimated 57.4 million HF-associated admissions occurred. Rates (95% confidence intervals) of admissions and in-hospital mortality among primary HF hospitalizations declined by an average annual rate of 3% (2.5%–3.5%) and 3.5% (2.9%–4.0%), respectively. Compared with 2001 to 2005, the average annual rate of decline in primary HF admissions …

Hydroxyurea Lowers The Frequency Of Sickle Cell Vaso-Occlusive Crises, Corey S. Macrander

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Charache S, Terrin ML, Moore RD, et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. N Engl J Med 1995;(332):1317-1322 doi: 10.1056/nejm199505183322001

Clopidogrel Alone Is Safer Than Clopidogrel And Aspirin For Secondary Prevention Of Acute Ischemic Stroke., Bradford J. Woelke, Daniel Angell Do, Katherine Litow Md

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Diener HC, Bogousslavsky J, Brass LM, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet. 2004;364(9431):331-337. doi: 10.1016/s0140-6736(04)16721-4

Quality? Safety? Stop Being Naïve., Rana K. Zaban Do, Steven Istephan, Jonathan Serman Md

Clinical Research in Practice: The Journal of Team Hippocrates

The first day of our inpatient medicine rotation, the Emergency Department (ED) admitted a patient to a general medical floor without notifying our rounding team. We used the institution’s system improvement tracking software to draw attention to communication breakdown in the interest of patient safety. This piece illustrates how there is a prominent hierarchy in medicine; it is inherent to the framework of the way in which hospitals function. A discussion ensues with our attending physician supervisor on our patient medicine service. During this discussion, we ponder whether it is possible to impact quality and safety from our position as …

Treating Diabetic Ketoacidosis With Subcutaneous Insulin?, Marlene Aziza Azar

Clinical Research in Practice: The Journal of Team Hippocrates

The author examines the evidence for treating diabetic ketoacidosis with subcutaneous insulin vs IV insulin.

Low Molecular-Weight Heparin Is Better Than Warfarin For Prevention Of Recurrent Venous Thromboembolism In Cancer Patients, Sarah Choi

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Lee AYY, Levin MN, Bake RI, et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003;349:146-153. doi: 10.1056/NEJMoa025313

H3k4 Demethylase Kdm5b Regulates Global Dynamics Of Transcription Elongation And Alternative Splicing In Embryonic Stem Cells, Runsheng He, Benjamin L. Kidder

Oncology Faculty Publications

Epigenetic regulation of chromatin plays a critical role in controlling embryonic stem (ES) cell selfrenewal and pluripotency. However, the roles of histone demethylases and activating histone modifications such as trimethylated histone 3 lysine 4 (H3K4me3) in transcriptional events such as RNA polymerase II (RNAPII) elongation and alternative splicing are largely unknown. In this study, we show that KDM5B, which demethylates H3K4me3, plays an integral role in regulating RNAPII occupancy, transcriptional initiation and elongation, and alternative splicing events in ES cells. Depletion of KDM5B leads to altered RNAPII promoter occupancy, and decreased RNAPII initiation and elongation rates at active genes and …

Galactose And Its Metabolites Deteriorate Metaphase Ii Mouse Oocyte Quality And Subsequent Embryo Development By Disrupting The Spindle Structure, Mili Thakur, Faten Shaeib, Sana N. Khan, Hamid-Reza Kohan-Ghader, Roohi Jeelani, Sarah R. Aldhaheri, Bernard Gonik, Husam M. Abu-Soud

C.S. Mott Center Research Publications

Premature ovarian insufficiency (POI) is a frequent long-term complication of classic galactosemia. The majority of women with this disorder develop POI, however rare spontaneous pregnancies have been reported. Here, we evaluate the effect of D-galactose and its metabolites, galactitol and galactose 1-phosphate, on oocyte quality as well as embryo development to elucidate the mechanism through which these compounds mediate oocyte deterioration. Metaphase II mouse oocytes (n=240), with and without cumulus cells (CCs), were exposed for 4hours to D-galactose (2μM), galactitol (11μM) and galactose 1-phosphate (0.1mM), (corresponding to plasma concentrations in patients on galactoserestricted diet) and compared to controls. The treated …

Innate Immune Pathways Associated With Lung Radioprotection By Soy Isoflavones, Lisa M. Abernathy, Matthew D. Fountain, Michael C. Joiner, Gilda G. Hillman

Oncology Faculty Publications

Introduction: Radiation therapy for lung cancer causes pneumonitis and fibrosis. Soy isoflavones protect against radiation-induced lung injury, but the mediators of radio- protection remain unclear. We investigated the effect of radiation on myeloid-derived suppressor cells (MDSCs) in the lung and their modulation by soy isoflavones for a potential role in protection from radiation-induced lung injury.

Methods: BALB/c mice (5–6 weeks old) received a single 10 Gy dose of thoracic irra- diation and soy isoflavones were orally administrated daily before and after radiation at 1 mg/day. Arginase-1 (Arg-1) and nuclear factor κB (NF-κB) p65 were detected in lung tissue by western …

The Ethics Of Offering Futile Treatment, Rebekah L. Eddy, Viktoria Krajnc, Lauren Smith

Clinical Research in Practice: The Journal of Team Hippocrates

It important to acknowledge our own emotional biases and be cognizant of how we present evidence-based options to patients and their families, so that they may provide truly informed consent.

Stem Cell Therapy For End Stage Copd: A Cautionary Tale Of Direct-To-Consumer Advertising, Blake J. Arthurs, Scott Yaekle

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Weiss DJ, Casaburi R, Flannery R, LeRoux-Williams M, Tashkin DP. A placebo-controlled, randomized trial of mesenchymal stem cells in COPD. Chest. 2013;143(6):1590-1598. doi: 10.1378/chest.12-2094

It Is Reasonable To Recommended Intrapleural Alteplase For Loculated Pleural Effusions, Tricia Fernandez

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Thommi G, Shehan J, Robison K, Christensen M, Backemeyer L, McLeay M. A double blind randomized cross over trial comparing rate of decortication and efficacy of intrapleural instillation of alteplase vs placebo in patients with empyemas and complicated parapneumonic effusions. Respir Med. 2012;17(2):716-723. doi: 10.1016/j.rmed.2012.02.005

Combination Octreotide, Midodrine, And Albumin May Improve Survival In Patients With Hepatorenal Syndrome, But The Evidence Is Weak, Jacob Szafranski

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Skagen C, Einstein M, Lucey MR, Said A. Combination treatment with octreotide, midodrine, and albumin improves survival in patients with type 1 and type 2 hepatorenal syndrome. J Clin Gastroenterol. 2009 Aug;43(7):680-5. doi: 10.1097/MCG.0b013e318188947c

Manage Terminal Ileum Diverticulitis Comparably To Diverticulitis Elsewhere, James Yip

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Park HC, Lee BH. The management of terminal ileum diverticulitis. Am Surg. 2009 Dec;75(12):1199-202.

Functional Analysis Of Rad6 In Brca1 Wild Type And Brca1 Mutant Triple Negative Breast Cancer Drug Response, Brittany Haynes

Wayne State University Dissertations

TNBCs account for 15-20% of all breast and are unsuitable for common targeted therapies as they lack expression of estrogen, progesterone, and Her2/neu receptors. Cisplatin, a DNA damaging agent, is currently under clinical investigation for treatment of TNBCs and paclitaxel, a mitotic spindle poison, is a first-line treatment option for this disease. While both agents elicit therapeutic benefit BRCA1 mutation status, toxicity, and resistance are limiting factors. Rad6 functions as an E2 ubiquitin conjugating protein and its enzymatic activity is critical for its cellular function. Rad6 is known to play a critical role in the translesion synthesis (TLS) damage response …

Mechanisms Of Hormonal Regulation Of Invasiveness And Metastasis Of Luminal Breast Cancer, Thomas Mcfall

Wayne State University Dissertations

ABSTRACT

MECHANISMS OF HORMONAL REGULATION OF INVASIVENESS AND METASTASIS OF LUMINAL BREAST CANCER

By

THOMAS MCFALL

December 2017

Advisor: Dr. Manohar Ratnam

Major: Cancer Biology

Degree: Doctor of Philosophy

Over 20% of breast cancer cases present with distal metastasis and they are predominantly of luminal subtypes. As luminal breast cancer is relatively indolent, it is believed that progression to metastasis must occur over many years, generally well into post-menopausal years. Unfortunately, very little is known about the mechanisms by which these hormone receptor positive tumors metastasize, likely in part due to their slow metastatic rates in animal model systems as …

Anti-Cancer Effects Of Tocotrienols In Nsclc, Lichchavi Raj Raj

Wayne State University Dissertations

Lung cancer is one of the leading causes of death among cancers, with non-small cell lung cancer (NSCLC) accounting for 80-85% of all lung cancers and a five-year survival rate of 5 % at stage IIIB. Delta-tocotrienol (δT) including other tocotrienol isomers has been shown to exhibit anti-tumor activity via inhibition of different signaling pathways in tumors including NSCLC. Previously we reported that δT reduced cell invasion via inhibition of the Notch-1 and NF-κb pathway.

Matrix metallopeptidase 9 (MMP9) dependent cell migration and invasion are key processes in cancer metastasis. Hence, its suppression is a promising strategy for cancer therapeutics. …

The Effects Of Bone Marrow Adipocytes On Metabolic Regulation In Metastatic Prostate Cancer, Jonathan Diedrich

Wayne State University Dissertations

Bone is a preferential site of metastasis from prostate cancer (PCa). Although there have been many advances in therapeutic options for patients suffering from metastatic PCa, this disease remains incurable with an estimated five-year survival of 33%. To design effective therapeutic interventions for metastatic PCa, it is essential that we elucidate the molecular mechanisms responsible for tumor cell adaptation to and the ability to thrive within the bone metastatic niche. Age and obesity, conditions that increase adipocyte numbers in bone marrow, are risk factors for skeletal metastases from PCa; therefore, our laboratory is focused on the interactions between marrow adipocytes …

Pet Imaging Of Early Therapeutic Response In Solid Tumors, Stephanie J. Blocker

Wayne State University Dissertations

An important pillar of precision medicine for oncology is the ability to identify patients who respond to treatment early into their therapy. Positron emission tomography (PET) allows physicians and researchers to measure changes in tumor behavior prior to noticeable differences in morphology.

Objective: Determine the utility of multiple tracers for PET in assessing early changes in tumor activity that result from treatment.

Methods: Two tracers for PET were studied. 64Cu-labeled liposomes were used to assess changes in liposome delivery two solid colon tumors early into treatment with bevacizumab (Bev). 18F-FMAU thymidine analog (1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)thymine), was utilized to detect early response to …

New Mechanism Based Approaches For Treating Prostate Cancer, Rayna Rosati

Wayne State University Dissertations

Prostate cancer (PC) is generally dependent on the androgen signaling axis for tumor growth. PC is managed by androgen deprivation therapy (ADT). The tumors then frequently progress by restoring ADT-resistant AR signaling through mechanisms such as intratumoral androgen synthesis, overexpression of AR, expression of splice variants of AR and alteration in the balance of AR co-regulators. This stage of progression is termed castrate recurrent prostate cancer (CRPC). Moreover, ADT has many major undesirable acute and chronic side effects on various normal tissues. Therefore a more strategic therapy approach is one that would disrupt a functional arm of AR signaling critical …

Functions Of Atr/Mec1 In Meiosis And The Cell Cycle, Layne Weatherford

Wayne State University Dissertations

Mec1 is a protein kinase in S. cerevisiae that is critical for the DNA damage checkpoint response, and is the yeast orthologue of the human ATR protein. Cancer cells rely on ATR to arrest the cell cycle and allow sufficient time to repair DNA damage before proceeding through the cell cycle, and ATR inhibitors have been developed as possible anti-cancer agents. DBF4 is the regulatory subunit of DBF4-dependent kinase (DDK) that regulates initiation of DNA replication and is overexpressed in a number of different cancer types. To better understand ATR and DBF4 function, we took advantage of yeast genetics to …

Clinicopathology And Molecular Determinants Underlying Benign Breast And Breast Cancer Lesions, Andreana Holowatyj Holowatyj

Wayne State University Dissertations

Despite converging incidence rates for breast cancers by race, disparities in mortality persist where black women suffer from poorer prognosis compared to white counterparts. To understand the clinical, demographic, and molecular characteristics underlying these disparities, we examined differences among patients with breast cancer to understand the role of human epidermal growth factor receptor 2 (HER2) status, age, and race/ethnicity among women diagnosed with hormone receptor-positive breast cancer, and disparities in surgical therapy among female patients with early stage young-onset breast cancer. Benign breast disease, another known risk factor for breast cancer, includes a histological spectrum of lesions, could contribute to …