Medicine and Health Sciences Commons^™

New Oral Anticoagulants Are Not Superior To Warfarin In Secondary Prevention Of Stroke Or Transient Ischemic Attacks, But Lower The Risk Of Intracranial Bleeding: Insights From A Meta-Analysis And Indirect Treatment Comparisons, Partha Sardar, Saurav Chatterjee, Wen-Chih Wu, Edgar Lichstein, Joydeep Ghosh, Shamik Aikat, Debabrata Mukherjee

Internal Medicine Faculty Publications

PURPOSE: Patients with Atrial Fibrillation (AF) and prior stroke are classified as high risk in all risk stratification schemes. A systematic review and meta-analysis was performed to compare the efficacy and safety of New Oral Anticoagulants (NOACs) to warfarin in patients with AF and previous stroke or transient ischemic attack (TIA).

METHODS: Three randomized controlled trials (RCTs), including total 14527 patients, comparing NOACs (apixaban, dabigatran and rivaroxaban) with warfarin were included in the analysis. Primary efficacy endpoint was ischemic stroke, and primary safety endpoint was intracranial bleeding. Random-effects models were used to pool efficacy and safety data across RCTs. RevMan …

Application Of Flexible Bronchoscopy In Inhalation Lung Injury, Chong Bai, Haidong Huang, Xiaopeng Yao, Shihui Zhu, Bing Li, Jingqing Hang, Wei Zhang, Paul Zarogoulidis, Andreas Gschwendtner, Konstantinos Zarogoulidis, Qiang Li, Michael Simoff

Internal Medicine Faculty Publications

Background: As acute inhalational injury is an uncommon presentation to most institutions, a standard approach to its assessment and management, especially using flexible bronchoscopy, has not received significant attention. Methods: The objective of this study is to evaluate the value of using flexible bronchoscopy as part of the evaluation and management of patients with inhalational lung injury. Twenty-three cases of inhalational lung injury were treated in our three hospitals after a fire in a residential building. The twenty cases that underwent bronchoscopy as part of their management are included in this analysis. After admission, the first bronchoscopy was conducted within …

Asthma And Risk Of Non-Respiratory Tract Infection: A Population-Based Case-Control Study, Duk Won Bang, Hyeon J Yang, Eell Ryoo, Majdi N. Al-Hasan, Brian Lahr, Larry M. Baddour, Barbara P. Yawn, Young J. Juhn

Internal Medicine Faculty Publications

OBJECTIVES: Asthmatics have increased risks of airway-related infections. Little is known about whether this is true for non-airway-related serious infections such as Escherichia coli bloodstream infection (BSI). We assessed whether asthma is associated with a risk of developing community-acquired E coli BSI.

DESIGN: The study was designed as a population-based retrospective case-control study.

SETTING: This population-based study was conducted in Olmsted County, Minnesota.

PARTICIPANTS: The study included 259 all eligible community-acquired E coli BSI cases in Olmsted County, MN between 1998 and 2007 and 259 birthday-matched, gender-matched and residency-matched controls.

PRIMARY AND SECONDARY OUTCOME MEASURES: Only community-acquired E coli BSI …

Multicenter Study Of High-Dose Daptomycin For Treatment Of Enterococcal Infections, Anthony M. Casapao, Ravina Kullar, Susan L. Davis, Donald P. Levine, Jing J. Zhao, Brian A. Potoski, Debra A. Goff, Christopher W. Crank, John Segreti, George Sakoulas, Sara E. Cosgrove, Michael J. Rybak

Internal Medicine Faculty Publications

Enterococci are among the leading pathogens isolated in hospital-acquired infections. Current antimicrobial options for vancomycin-resistant enterococci (VRE) are limited. Prior data suggests that daptomycin > 6mg/kg/day may be used to treat enterococcal infections. We retrospectively evaluated the effectiveness and safety of high-dose daptomycin (HD-daptomycin) therapy (> 6 mg/kg) in a multicenter cohort of adult patients with enterococcal infections to describe the characteristics and outcomes. Two-hundred and forty-five patients were evaluated. Enterococcus faecium was identified in 175 (71%), followed by 49 (20%) Enterococcus faecalis and 21 (9%) Enterococcus spp., overall 204 (83%) were VRE. Enterococcal infections included bacteremia (173, 71%), intra-abdominal (35, …

Autophagy Is Involved In Oligodendroglial Precursor-Mediated Clearance Of Amyloid Peptide, Wenxia Li, Yifen Tang, Zhiqin Fan, Ya Meng, Guang Yang, Jia Luo, Zun-Ji Ke

Internal Medicine Faculty Publications

BACKGROUND: Accumulation of β-amyloid peptides is an important hallmark of Alzheimer's disease (AD). Tremendous efforts have been directed to elucidate the mechanisms of β-amyloid peptides degradation and develop strategies to remove β-amyloid accumulation. In this study, we demonstrated that a subpopulation of oligodendroglial precursor cells, also called NG2 cells, were a new cell type that can clear β-amyloid peptides in the AD transgene mice and in NG2 cell line.

RESULTS: NG2 cells were recruited and clustered around the amyloid plaque in the APPswe/PS1dE9 mice, which is Alzheimer's disease mouse model. In vitro, NG2 cell line and primary NG2 cells engulfed …

Bridging Storytelling Traditions With Digital Technology, Melany Cueva, Regina Kuhnley, Laura J. Revels, Katie Cueva, Mark B. Dignan, Anne P. Lanier

Internal Medicine Faculty Publications

Objective. The purpose of this project was to learn how Community Health Workers (CHWs) in Alaska perceived digital storytelling as a component of the “Path to Understanding Cancer” curriculum and as a culturally respectful tool for sharing cancer-related health messages.

Design. A pre-course written application, end-of-course written evaluation, and internet survey informed this project.

Methods. Digital storytelling was included in seven 5-day cancer education courses (May 2009–2012) in which 67 CHWs each created a personal 2–3 minute cancer-related digital story. Participant-chosen digital story topics included tobacco cessation, the importance of recommended cancer screening exams, cancer survivorship, loss, …

Telenovela: An Innovative Colorectal Cancer Screening Health Messaging Tool, Melany Cueva, Regina Kuhnley, Jozieta Slatton, Mark B. Dignan, Emily Underwood, Kate Landis

Internal Medicine Faculty Publications

Background. Alaska Native people have nearly twice the rate of colorectal cancer (CRC) incidence and mortality as the US White population.

Objective. Building upon storytelling as a culturally respectful way to share information among Alaska Native people, a 25-minute telenovela-style movie, What's the Big Deal?, was developed to increase CRC screening awareness and knowledge, role-model CRC conversations, and support wellness choices.

Design. Alaska Native cultural values of family, community, storytelling, and humor were woven into seven, 3–4 minute movie vignettes. Written post-movie viewing evaluations completed by 71.3% of viewers (305/428) were collected at several venues, including the …

Intratumoral Chemotherapy For Lung Cancer: Re-Challenge Current Targeted Therapies, Wolfgang Hohenforst-Schmidt, Paul Zarogoulidis, Kaid Darwiche, Thomas Vogl, Eugene P. Goldberg, Haidong Huang, Michael Simoff, Qiang Li, Robert Browning, Francis J. Turner, Patrick Le Pivert, Dionysios Spyratos, Konstantinos Zarogoulidis, Seyhan I. Celikoglu, Firuz Celikoglu, Johannes Brachmann

Internal Medicine Faculty Publications

Strategies to enhance the already established doublet chemotherapy regimen for lung cancer have been investigated for more than 20 years. Initially, the concept was to administer chemotherapy drugs locally to the tumor site for efficient diffusion through passive transport within the tumor. Recent advances have enhanced the diffusion of pharmaceuticals through active transport by using pharmaceuticals designed to target the genome of tumors. In the present study, five patients with non-small cell lung cancer epidermal growth factor receptor (EGFR) negative stage IIIa–IV International Union Against Cancer 7 (UICC-7), and with Eastern Cooperative Oncology Group (ECOG) 2 scores were administered platinum-based …

Diaphragm Weakness In Mechanically Ventilated Critically Ill Patients, Gerald S. Supinski, Leigh Ann Callahan

Internal Medicine Faculty Publications

INTRODUCTION: Studies indicate that mechanically ventilated patients develop significant diaphragm muscle weakness, but the etiology of weakness and its clinical impact remain incompletely understood. We assessed diaphragm strength in mechanically ventilated medical ICU patients, correlated the development of diaphragm weakness with multiple clinical parameters, and examined the relationship between the level of diaphragm weakness and patient outcomes.

METHODS: Transdiaphragmatic twitch pressure (PdiTw) in response to bilateral magnetic stimulation of the phrenic nerves was measured. Diaphragm weakness was correlated with the presence of infection, blood urea nitrogen, albumin, and glucose levels. The relationship of diaphragm strength to patient outcomes, including mortality …

Green Tea Polyphenols And Sulfasalazine Have Parallel Anti-Inflammatory Properties In Colitis Models, Helieh S. Oz, Theresa Chen, Willem J.S. De Villiers

Internal Medicine Faculty Publications

Background: There is no cure for autoimmune chronic inflammatory bowel disease (IBD). IBD patients commonly use complementary and alternative medications of which the safety, efficacy, and interaction with standard-of-care therapies are not fully known. Thus the consequences can become life-threatening. Sulfasalazine commonly used in IBD, potentially has severe adverse effects, including infertility, pulmonary fibrosis, lack of response, and ultimately patients may require intestinal resection. We hypothesized that green tea polyphenols (GrTP, EGCG) and sulfasalazine have similar anti-inflammatory properties.

Methods: BALB/c mice received Dextran sodium sulfate (DSS) to induce colitis (ulcerative colitis model). Exposure of IL-10 deficient mice (BALB/c-background) to normal …

Bioactive Lipids And Cationic Antimicrobial Peptides As New Potential Regulators For Trafficking Of Bone Marrow-Derived Stem Cells In Patients With Acute Myocardial Infarction, Anush V. Karapetyan, Yuri M. Klyachkin, Samy Selim, Manjula Sunkara, Khaled M. Ziada, Donald A. Cohen, Ewa K. Zuba-Surma, Janina Ratajczak, Susan S. Smyth, Mariusz Z. Ratajczak, Andrew J. Morris, Ahmed Abdel-Latif

Internal Medicine Faculty Publications

Acute myocardial infarction (AMI) triggers mobilization of stem cells from bone marrow (BM) into peripheral blood (PB). Based on our observation that the bioactive sphingophospholipids, sphingosine-1 phosphate (S1P), and ceramide-1 phosphate (C1P) regulate trafficking of hematopoietic stem cells (HSCs), we explored whether they also direct trafficking of non-hematopoietic stem cells (non-HSCs). We detected a 3–6-fold increase in circulating CD34+, CD133+, and CXCR4+ lineage-negative (Lin−)/CD45− cells that are enriched in non-HSCs [including endothelial progenitors (EPCs) and very small embryonic-like stem cells (VSELs)] in PB from AMI patients (P<0.05 vs. controls). Concurrently, we measured a 3-fold increase in S1P and C1P levels in plasma from AMI patients. At the same time, plasma obtained at hospital admission and 6 h after AMI strongly chemoattracted human BM-derived CD34+/Lin− and CXCR4+/Lin− cells in Transwell chemotaxis assays. This effect of plasma was blunted after depletion of S1P level by charcoal stripping and was further inhibited by the specific S1P1 receptor antagonist such as W146 and VPC23019. We also noted that the expression of S1P receptor 1 (S1P1), which is dominant in naïve BM, is reduced after the exposure to S1P at concentrations similar to the plasma S1P levels in patients with AMI, thus influencing the role of S1P in homing to the injured myocardium. Therefore, we examined mechanisms, other than bioactive lipids, that may contribute to the homing of BM non-HSCs to the infarcted myocardium. Hypoxic cardiac tissue increases the expression of cathelicidin and β-2 defensin, which could explain why PB cells isolated from patients with AMI migrated more efficiently to a low, yet physiological, gradient of stromal-derived factor-1 in Transwell migration assays. Together, these observations suggest that while elevated S1P and C1P levels early in the course of AMI may trigger mobilization of non-HSCs into PB, cathelicidin and β-2 defensin could play an important role in their homing to damaged myocardium.

Necrotizing Sarcoid Granulomatosis With Hemoptysis: A Case Report And Literature Review, Haidong Huang, Chen Li, Chong Bai, Qiang Li, Weiqiang Zheng, Zhi Zhu, Paul Zarogoulidis, Konstantinos Zarogoulidis, Andreas Gschwendtner, Wolfgang Hohenforst-Schmidt, Michael Simoff

Internal Medicine Faculty Publications

We present a case of 39-year-old male with the symptoms of fever, cough, chest pain and bloody phlegm, whose chest CT showed multiple subpleural nodules and inflammatory infiltration. Video-Assisted Thoracic Surgery ( VATS ) for right subplural nodule was performed and confirmed the diagnosis of necrotizing sarcoid granulomatosis. Prednisolone was administered and the symptoms were under control untill the occurrence of intermittent hemoptysis after 10 months. Chest CT and bronchoscope revealed the right lower lobe nodule with intraluminal necrotic tissue in the right lower lobe posterior basal segment respectively. Fatal hemoptysis happened during endobronchial biopsy by flexible bronchoscope forcep. Based …

Lrp5 And Lrp6 Exert Overlapping Functions In Osteoblasts During Postnatal Bone Acquisition, Ryan C. Riddle, Cassandra R. Diegel, Julie M. Leslie, Kyle K. Van Koevering, Marie-Claude Faugere, Thomas L. Clemens, Bart O. Williams

Internal Medicine Faculty Publications

The canonical Wnt signaling pathway is critical for skeletal development and maintenance, but the precise roles of the individual Wnt co-receptors, Lrp5 and Lrp6, that enable Wnt signals to be transmitted in osteoblasts remain controversial. In these studies, we used Cre-loxP recombination, in which Cre-expression is driven by the human osteocalcin promoter, to determine the individual contributions of Lrp5 and Lrp6 in postnatal bone acquisition and osteoblast function. Mice selectively lacking either Lrp5 or Lrp6 in mature osteoblasts were born at the expected Mendelian frequency but demonstrated significant reductions in whole-body bone mineral density. Bone architecture measured by microCT revealed …

Osteoblast-Restricted Disruption Of The Growth Hormone Receptor In Mice Results In Sexually Dimorphic Skeletal Phenotypes, Vandana Singhal, Brian C. Goh, Mary L. Bouxsein, Marie-Claude Faugere, Douglas J. Digirolamo

Internal Medicine Faculty Publications

Growth hormone (GH) exerts profound anabolic actions during postnatal skeletal development, in part, through stimulating the production of insulin-like growth factor-1 (IGF-1) in liver and skeletal tissues. To examine the requirement for the GH receptor (GHR) in osteoblast function in bone, we used Cre-LoxP methods to disrupt the GHR from osteoblasts, both in vitro and in vivo. Disruption of GHR from primary calvarial osteoblasts in vitro abolished GH-induced signaling, as assessed by JAK2/STAT5 phosphorylation, and abrogated GH-induced proliferative and anti-apoptotic actions. Osteoblasts lacking GHR exhibited reduced IGF-1-induced Erk and Akt phosphorylation and attenuated IGF-1-induced proliferation and anti-apoptotic action. In …

An Acacb Variant Implicated In Diabetic Nephropathy Associates With Body Mass Index And Gene Expression In Obese Subjects, Lijun Ma, Mariana Murea, James A. Snipes, Alejandra Marinelarena, Jacqueline Krüger, Pamela J. Hicks, Kurt A. Langberg, Meredith A. Bostrom, Jessica N. Cooke, Daisuke Suzuki, Tetsuya Babazono, Takashi Uzu, Sydney C. W. Tang, Ashis K. Mondal, Neeraj K. Sharma, Sayuko Kobes, Peter A. Antinozzi, Matthew Davis, Swapan K. Das, Neda Rasouli, Philip A. Kern, Nathan J. Shores, Lawrence L. Rudel, Matthias Blüher, Michael Stumvoll, Donald W. Bowden, Shiro Maeda, John S. Parks, Peter Kovacs, Robert L. Hanson, Leslie J. Baier, Steven C. Elbein, Barry I. Freedman

Internal Medicine Faculty Publications

Acetyl coenzyme A carboxylase B gene (ACACB) single nucleotide polymorphism (SNP) rs2268388 is reproducibly associated with type 2 diabetes (T2DM)-associated nephropathy (DN). ACACB knock-out mice are also protected from obesity. This study assessed relationships between rs2268388, body mass index (BMI) and gene expression in multiple populations, with and without T2DM. Among subjects without T2DM, rs2268388 DN risk allele (T) associated with higher BMI in Pima Indian children (n = 2021; p-additive = 0.029) and African Americans (AAs) (n = 177; p-additive = 0.05), with a trend in European Americans (EAs) (n = 512; p-additive = 0.09), but not Germans (n …

Bronchial Thermoplasty, Javier Diaz-Mendoza, Chong Bai, Hai-Dong Huang, Michael J. Simoff

Internal Medicine Faculty Publications

No abstract provided.

Role Of 18F-Fdg Pet Scan In Rheumatoid Lung Nodule: Case Report And Review Of The Literature, Christine L. Chhakchhuak, Mehdi Khosravi, Kristine M. Lohr

Internal Medicine Faculty Publications

Flourine-18 fluoro-2-deoxy-glucose (¹⁸F-FDG) positron emission tomography combined with computed tomography (PET/CT) is a useful test for the management of malignant conditions. Inflammatory and infectious processes, however, can cause increased uptake on PET scanning, often causing diagnostic dilemmas. This knowledge is important to the rheumatologist not only because of the inflammatory conditions we treat but also because certain rheumatic diseases impose an increased risk of malignancy either due to the disease itself or as a consequence of medications used to treat the rheumatic diseases. There is an increasing body of evidence investigating the role of PET scans in inflammatory …