Digital Commons Network^™

Patients' Perceptions And Patient-Reported Outcomes In Progressive-Fibrosing Interstitial Lung Diseases, Jeffrey J. Swigris, Kevin K. Brown, Rayid Abdulqawi, Ketan Buch, Daniel F. Dilling, Dirk Koschel, Krishna Thavarajah, Rade Tomic, Yoshikazu Inoue

Internal Medicine Faculty Publications

The effects of interstitial lung disease (ILD) create a significant burden on patients, unsettling almost every domain of their lives, disrupting their physical and emotional well-being and impairing their quality of life (QoL). Because many ILDs are incurable, and there are limited reliably-effective, life-prolonging treatment options available, the focus of many therapeutic interventions has been on improving or maintaining how patients with ILD feel and function, and by extension, their QoL. Such patient-centred outcomes are best assessed by patients themselves through tools that capture their perceptions, which inherently incorporate their values and judgements. These patient-reported outcome measures (PROs) can be …

Patients' Perceptions And Patient-Reported Outcomes In Progressive-Fibrosing Interstitial Lung Diseases, Jeffrey J. Swigris, Kevin K. Brown, Rayid Abdulqawi, Ketan Buch, Daniel F. Dilling, Dirk Koschel, Krishna Thavarajah, Rade Tomic, Yoshikazu Inoue

Internal Medicine Faculty Publications

The effects of interstitial lung disease (ILD) create a significant burden on patients, unsettling almost every domain of their lives, disrupting their physical and emotional well-being and impairing their quality of life (QoL). Because many ILDs are incurable, and there are limited reliably-effective, life-prolonging treatment options available, the focus of many therapeutic interventions has been on improving or maintaining how patients with ILD feel and function, and by extension, their QoL. Such patient-centred outcomes are best assessed by patients themselves through tools that capture their perceptions, which inherently incorporate their values and judgements. These patient-reported outcome measures (PROs) can be …

Large-Scale Genome-Wide Meta-Analysis Of Polycystic Ovary Syndrome Suggests Shared Genetic Architecture For Different Diagnosis Criteria, Felix Day, Tugce Karaderi, Michelle R. Jones, Cindy Meun, Chunyan He, Alex Drong, Peter Kraft, Nan Lin, Hongyan Huang, Linda Broer, Reedik Magi, Richa Saxena, Triin Laisk, Margrit Urbanek, M. Geoffrey Hayes, Gudmar Thorleifsson, Juan Fernandez-Tajes, Anubha Mahajan, Benjamin H. Mullin, Bronwyn G. A. Stuckey, Timothy D. Spector, Scott G. Wilson, Mark O. Goodarzi, Lea Davis, Barbara Obermayer-Pietsch, André G. Uitterlinden, Verneri Anttila, Benjamin M. Neale, Marjo-Riitta Jarvelin, Bart Fauser

Internal Medicine Faculty Publications

Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Affected women frequently have metabolic disturbances including insulin resistance and dysregulation of glucose homeostasis. PCOS is diagnosed with two different sets of diagnostic criteria, resulting in a phenotypic spectrum of PCOS cases. The genetic similarities between cases diagnosed based on the two criteria have been largely unknown. Previous studies in Chinese and European subjects have identified 16 loci associated with risk of PCOS. We report a fixed-effect, inverse-weighted-variance meta-analysis from 10,074 PCOS cases and 103,164 controls of European ancestry and characterisation of PCOS related …

Clopidogrel Versus Newer P2y12 Antagonists For Percutaneous Coronary Intervention In Patients With Out-Of-Hospital Cardiac Arrest Managed With Therapeutic Hypothermia: A Meta-Analysis, Ayman Elbadawi, Islam Y. Elgendy, Ahmed H. Mohamed, Kirolos Barssoum, Erfan Alotaki, Gbolahan O. Ogunbayo, Khaled M. Ziada

Internal Medicine Faculty Publications

Introduction: The impact of therapeutic hypothermia (TH) on outcomes of percutaneous coronary intervention (PCI) and the optimal antiplatelet treatment remains debatable.

Methods: Electronic databases were searched for randomized trials and observational studies to evaluate the available clinical evidence comparing the use of clopidogrel versus newer P2Y12 antagonists in cases of TH after PCI. The primary outcome was in-hospital definite stent thrombosis while the secondary outcomes were in-hospital mortality and major bleeding. Fixed-effects risk ratios (RRs) were estimated using Mantel–Haenszel method.

Results: The final analysis included five studies with a total of 290 patients. There was no difference in the incidence …

Validation Of Near Infrared Fluorescence (Nirf) Probes In Vivo With Dual Laser Nirf Endoscope, Manisha Shrivastav, Elias Gounaris, Mohammad W. Khan, Jeffrey Ko, Stacy H. Ryu, Matthew Bogyo, Andrew Larson, Terrence A. Barrett, David J. Bentrem

Internal Medicine Faculty Publications

Purpose

The development of NIRF cathepsin activity probes offered the ability to visualize tumor associated tumor reaction and act as a surrogate marker to delineate the dysplastic lesions. One major type is a NIRF substrate of cathepsins (SBP), which is involved in catalytic way to produce high levels of fluorescence emission. The other major type (ABP) reacts with active cathepsins in stoichiometric manner since they bind covalently with their active center. Little is known about the sensitivity and the specificity of the NIRF probes to detect autochthonous developed dysplastic lesions. Dual laser NIRF endoscope provides a good tool to determine …

Are We Missing The Elephant In The Room? A Case For Thyroid Cancer Overdiagnosis As The Etiology For Its Increasing Incidence In India, Janeesh Sekkath Veedu, Aju Mathew

Internal Medicine Faculty Publications

No abstract provided.

Detection Of (1,3)-Β-D-Glucan In Cerebrospinal Fluid In Histoplasma Meningitis, Thein Myint, Felicia C. Chow, Karen C. Bloch, Luke Raymond-Guillen, Thomas E. Davis, Patty W. Wright, Laila Woc-Colburn, Raed N. Khairy, Alan C. Street, Tomotaka Yamamoto, Amanda Albers, L. Joseph Wheat, Chadi A. Hage

Internal Medicine Faculty Publications

The diagnosis of central nervous system (CNS) histoplasmosis is often difficult. Although cerebrospinal fluid (CSF) (1,3)-β-d-glucan (BDG) is available as a biological marker for the diagnosis of fungal meningitis, there are limited data on its use for the diagnosis of Histoplasma meningitis. We evaluated CSF BDG detection, using the Fungitell assay, in patients with CNS histoplasmosis and controls. A total of 47 cases and 153 controls were identified. The control group included 13 patients with a CNS fungal infection other than histoplasmosis. Forty-nine percent of patients with CNS histoplasmosis and 43.8% of controls were immunocompromised. The median CSF …

Abducens Nerve Palsy As Initial Presentation Of Multiple Myeloma And Intracranial Plasmacytoma, Elochukwu Ibekwe, Neil Bradford Horsley, Lan Jiang, Nadine-Stella Achenjang, Azubuogu Anudu, Zeeshan Akhtar, Karina G. Chornenka, Gregory P. Monohan, Yevgen G. Chornenkyy

Internal Medicine Faculty Publications

Central Nervous System (CNS) involvement in multiple myeloma and/or multifocal solitary plasmacytoma is rare. Although they are unique entities, multiple myeloma (MM) and plasmacytoma represent a spectrum of plasma cell neoplastic diseases that can sometimes occur concurrently. Plasmacytomas very often present as late-stage sequelae of MM. In this case report, we report a 53-year-old female presenting with right abducens cranial nerve (CN) VI palsy as an initial presentation secondary to lesion of the right clivus.

Autotaxin-Lpa Signaling Contributes To Obesity-Induced Insulin Resistance In Muscle And Impairs Mitochondrial Metabolism, Kenneth D'Souza, Carine Nzirorera, Andrew M. Cowie, Geena P. Varghese, Purvi Trivedi, Thomas O. Eichmann, Dipsikha Biswas, Mohamed Touaibia, Andrew J. Morris, Vassilis Aidinis, Daniel A. Kane, Thomas Pulinilkunnil, Petra C. Kienesberger

Internal Medicine Faculty Publications

Autotaxin (ATX) is an adipokine that generates the bioactive lipid, lysophosphatidic acid (LPA). ATX-LPA signaling has been implicated in diet-induced obesity and systemic insulin resistance. However, it remains unclear whether the ATX-LPA pathway influences insulin function and energy metabolism in target tissues, particularly skeletal muscle, the major site of insulin-stimulated glucose disposal. The objective of this study was to test whether the ATX-LPA pathway impacts tissue insulin signaling and mitochondrial metabolism in skeletal muscle during obesity. Male mice with heterozygous ATX deficiency (ATX^+/−) were protected from obesity, systemic insulin resistance, and cardiomyocyte dysfunction following high-fat high-sucrose (HFHS) feeding. …

A Case Of Co-Secreting Tsh And Growth Hormone Pituitary Adenoma Presenting With A Thyroid Nodule, Laura Hamilton Adams, Derick Adams

Internal Medicine Faculty Publications

Co-secreting TSH and growth hormone pituitary adenomas are rare. We present a case of a 55-year-old woman who presented with symptoms of neck fullness. Ultrasound revealed multiple thyroid nodules and examination revealed several clinical features of acromegaly. She was found to have a co-secreting TSH and growth hormone pituitary macroadenoma. She underwent surgical resection followed by gamma knife radiation, which resulted in complete remission of her TSH and GH-secreting adenoma.

High-Density Lipoprotein Inhibits Serum Amyloid A-Mediated Reactive Oxygen Species Generation And Nlrp3 Inflammasome Activation, Preetha Shridas, Maria C. De Beer, Nancy R. Webb

Internal Medicine Faculty Publications

Serum amyloid A (SAA) is a high-density apolipoprotein whose plasma levels can increase more than 1000-fold during a severe acute-phase inflammatory response and are more modestly elevated in chronic inflammation. SAA is thought to play important roles in innate immunity, but its biological activities have not been completely delineated. We previously reported that SAA deficiency protects mice from developing abdominal aortic aneurysms (AAAs) induced by chronic angiotensin II (AngII) infusion. Here, we report that SAA is required for AngII-induced increases in interleukin-1β (IL-1β), a potent proinflammatory cytokine that is tightly controlled by the Nod-like receptor protein 3 (NLRP3) inflammasome and …

What Insights Do Patients And Caregivers Have On Acute Kidney Injury And Posthospitalization Care? A Single-Centre Qualitative Study From Toronto, Canada, Samuel A. Silver, Marianne Saragosa, Neill K. Adhikari, Chaim M. Bell, Ziv Harel, Andrea Harvey, Abhijat Kitchlu, Javier A. Neyra, Ron Wald, Lianne Jeffs

Internal Medicine Faculty Publications

Objectives Hospitalisation with acute kidney injury (AKI) is associated with short-term and long-term adverse events, but patient and caregiver experiences with AKI are not well described. We sought to better understand patient and caregiver perspectives after a hospitalisation with AKI to inform discharge strategies that may improve outcomes for this high-risk population.

Design Qualitative study with semistructured interviews.

Setting Tertiary care hospital in Toronto, Ontario, Canada.

Participants Adult patients (n=15) who survived a hospitalisation with Kidney Disease Improving Global Outcomes stage 2 or 3 AKI from May to December 2016. We also interviewed five patient caregivers. We required patients to …

Isolated Sporothrix Schenckii Monoarthritis, Aram Barbaryan, Wissam El Atrouni, Stefania Bailuc, Matthew W. Jones, Maharshi Bhakta, Khaldoun Haj Mahmoud, Aibek E. Mirrakhimov

Internal Medicine Faculty Publications

Sporothrix schenkii sensu lato is a rare cause of arthritis. Its course is indolent with lack of constitutional symptoms resulting in delayed presentation and diagnosis. It is a dimorphic fungus found ubiquitously in sphagnum moss, decaying vegetation, soil, and hay. Inoculation of dirt into the skin and soft tissues and, in rare instances, inhalation of aerosolized conidia from soil and plants can lead to infection. Subacute and chronic involvement of skin and subcutaneous tissues is the most common manifestation of sporotrichosis in immunocompetent hosts. In patients with underlying risk factors (HIV, alcoholism, diabetes mellitus, organ transplant patients, immunosuppressive medications, steroids, …

First Results On Survival From A Large Phase 3 Clinical Trial Of An Autologous Dendritic Cell Vaccine In Newly Diagnosed Glioblastoma, Linda M. Liau, Keyoumars Ashkan, David D. Tran, Jian L. Campian, John E. Trusheim, Charles S. Cobbs, Jason A. Heth, Michael Salacz, Sarah Taylor, Stacy D. D'Andre, Fabio M. Iwamoto, Edward J. Dropcho, Yaron A. Moshel, Kevin A. Walter, Clement P. Pillainayagam, Robert Aiken, Rekha Chaudhary, Samuel A. Goldlust, Daniela A Bota, Paul Duic, Jai Grewal, Heinrich Elinzano, Steven A. Toms, Kevin O. Lillehei, Tom Mikkelsen, Tobias Walbert, Steven R. Abram, Andrew J. Brenner, Steven Brem, Matthew G. Ewend, John L. Villano

Internal Medicine Faculty Publications

Background: Standard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax^®-L) to standard therapy for newly diagnosed glioblastoma.

Methods: After surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99). Following recurrence, all patients were allowed to receive DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); the secondary endpoint was overall survival (OS).

Results: For the intent-to-treat (ITT) population (n = 331), median OS (mOS) was 23.1 months …

Synaptic Phospholipids As A New Target For Cortical Hyperexcitability And E/I Balance In Psychiatric Disorders, Carine Thalman, Guilherme Horta, Lianyong Qiao, Heiko Endle, Irmgard Tegeder, Hong Cheng, Gregor Laube, Torfi Sigurdsson, Maria Jelena Hauser, Stefan Tenzer, Ute Distler, Junken Aoki, Andrew J. Morris, Gerd Geisslinger, Jochen Röper, Sergei Kirischuk, Heiko J. Luhmann, Konstantin Radyushkin, Robert Nitsch, Johannes Vogt

Internal Medicine Faculty Publications

Lysophosphatidic acid (LPA) is a synaptic phospholipid, which regulates cortical excitation/inhibition (E/I) balance and controls sensory information processing in mice and man. Altered synaptic LPA signaling was shown to be associated with psychiatric disorders. Here, we show that the LPA-synthesizing enzyme autotaxin (ATX) is expressed in the astrocytic compartment of excitatory synapses and modulates glutamatergic transmission. In astrocytes, ATX is sorted toward fine astrocytic processes and transported to excitatory but not inhibitory synapses. This ATX sorting, as well as the enzymatic activity of astrocyte-derived ATX are dynamically regulated by neuronal activity via astrocytic glutamate receptors. Pharmacological and genetic ATX inhibition …

Capecitabine And Temozolomide In Neuroendocrine Tumor Of Unknown Primary, Aman Chauhan, Zainab Farooqui, Leaundra Murray, Heidi L. Weiss, Zin W. Myint, Arun Kumar A. Raajasekar, B. Mark Evers, Susanne M. Arnold, Lowell B. Anthony

Internal Medicine Faculty Publications

Incidence of low grade well-differentiated neuroendocrine tumors (NET) is on the rise. The North American Neuroendocrine Tumor Society estimates that the United States has more than 150,000 gastroenteropancreatic NET patients. About 10% of metastatic NETs can be unknown primary, and due to their rarity, dedicated treatment algorithms and regimens are not defined. Combination of capecitabine and temozolomide (CAPTEM) is one of the systemic treatments used in gastroenteropancreatic NETs. We explored clinical activity of CAPTEM in NET of unknown primary. Methods. Retrospective review of NET of unknown primary managed at the University of Kentucky over the past five years (2012–2016). …

Analysis Of College Students’ Personal Health Information Activities: Online Survey, Sujin Kim, Donghee Sinn, Sue Yeon Syn

Internal Medicine Faculty Publications

Background: With abundant personal health information at hand, individuals are faced with a critical challenge in evaluating the informational value of health care records to keep useful information and discard that which is determined useless. Young, healthy college students who were previously dependents of adult parents or caregivers are less likely to be concerned with disease management. Personal health information management (PHIM) is a special case of personal information management (PIM) that is associated with multiple interactions among varying stakeholders and systems. However, there has been limited evidence to understand informational or behavioral underpinning of the college students’ PHIM activities, …

N-Terminal Pro-B-Type Natriuretic Peptide And Microsize Myocardial Infarction Risk In The Reasons For Geographic And Racial Differences In Stroke Study, Madeline R. Sterling, Raegan W. Durant, Joanna Bryan, Emily B. Levitan, Todd M. Brown, Yulia Khodneva, Stephen P. Glasser, Joshua S. Richman, George Howard, Mary Cushman, Monika M. Safford

Internal Medicine Faculty Publications

Background: N-terminal pro B-type peptide (NT-proBNP) has been associated with risk of myocardial infarction (MI), but less is known about the relationship between NT-proBNP and very small non ST-elevation MI, also known as microsize MI. These events are now routinely detectable with modern troponin assays and are emerging as a large proportion of all MI. Here, we sought to compare the association of NT-proBNP with risk of incident typical MI and microsize MI in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

Methods: The REGARDS Study is a national cohort of 30,239 US community-dwelling black and white …

Quality Of Life During Treatment With Chemohormonal Therapy: Analysis Of E3805 Chemohormonal Androgen Ablation Randomized Trial In Prostate Cancer, Alicia K. Morgans, Yu-Hui Chen, Christopher J. Sweeney, David F. Jarrard, Elizabeth R. Plimack, Benjamin A. Gartrell, Michael A. Carducci, Maha Hussain, Jorge A. Garcia, David Cella, Robert S. Dipaola, Linda J. Patrick-Miller

Internal Medicine Faculty Publications

Purpose

Chemohormonal therapy with docetaxel and androgen deprivation therapy (ADT+D) for metastatic hormone-sensitive prostate cancer improves overall survival as compared with androgen deprivation therapy (ADT) alone. We compared the quality of life (QOL) between patients with metastatic hormone-sensitive prostate cancer who were treated with ADT+D and those who were treated with ADT alone.

Methods

Men were randomly assigned to ADT+ D (six cycles) or to ADT alone. QOL was assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P), FACT-Taxane, Functional Assessment of Chronic Illness Therapy-Fatigue, and the Brief Pain Inventory at baseline and at 3, 6, 9, and 12 months. The …

Chemohormonal Therapy In Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis Of The Randomized Phase Iii E3805 Chaarted Trial, Christos E. Kyriakopoulos, Yu-Hui Chen, Michael A. Carducci, Glenn Liu, David F. Jarrard, Noah M. Hahn, Daniel H. Shevrin, Robert Dreicer, Maha Hussain, Mario Eisenberger, Manish Kohli, Elizabeth R. Plimack, Nicholas J. Vogelzang, Joel Picus, Matthew M. Cooney, Jorge A. Garcia, Robert S. Dipaola, Christopher J. Sweeney

Internal Medicine Faculty Publications

Purpose

Docetaxel added to androgen-deprivation therapy (ADT) significantly increases the longevity of some patients with metastatic hormone-sensitive prostate cancer. Herein, we present the outcomes of the CHAARTED (Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) trial with more mature follow-up and focus on tumor volume.

Patients and Methods

In this phase III study, 790 patients with metastatic hormone-sensitive prostate cancer were equally randomly assigned to receive either ADT in combination with docetaxel 75 mg/mm² for up to six cycles or ADT alone. The primary end point of the study was overall survival (OS). Additional …

Early Relapse After Autologous Hematopoietic Cell Transplantation Remains A Poor Prognostic Factor In Multiple Myeloma But Outcomes Have Improved Over Time, Shaji K. Kumar, Angela Dispenzieri, Raphael Fraser, Fei Mingwei, Gorgun Akpek, Robert Cornell, Mohamed Kharfan-Dabaja, Cesar Freytes, Shahrukh Hashmi, Gerhard C. Hildebrandt, Leona Holmberg, Robert Kyle, Hillard Lazarus, Cindy Lee, Jospeh Mikhael, Taiga Nishihori, Jason Tay, Saad Usmani, David Vesole, Ravi Vij, Baldeep Wirk, Amrita Krishnan, Cristina Gasparetto, Tomer Mark, Yago Nieto, Parameswaran Hari, Anita D'Souza

Internal Medicine Faculty Publications

Duration of initial disease response remains a strong prognostic factor in multiple myeloma (MM) particularly for upfront autologous hematopoietic cell transplant (AHCT) recipients. We hypothesized that new drug classes and combinations employed prior to AHCT as well as after post-AHCT relapse may have changed the natural history of MM in this population. We analyzed the Center for International Blood and Marrow Transplant Research database to track overall survival (OS) of MM patients receiving single AHCT within 12 months after diagnosis (N=3256) and relapsing early post-AHCT (< 24 months), and to identify factors predicting for early vs late relapses (24−48 months post-AHCT). Over three periods (2001–2004, 2005–2008, 2009–2013), patient characteristics were balanced except for lower proportion of Stage III, higher likelihood of one induction therapy with novel triplets and higher rates of planned post-AHCT maintenance over time. The proportion of patients relapsing early was stable over time at 35–38%. Factors reducing risk of early relapse included lower stage, chemosensitivity, transplant after 2008 and post-AHCT maintenance. Shorter post-relapse OS was associated with early relapse, IgA MM, Karnofsky < 90, stage III, > 1 line of induction and lack of maintenance. Post-AHCT early relapse remains …

Mobilization Of Hematopoietic Stem Cells As A Result Of Innate Immunity-Mediated Sterile Inflammation In The Bone Marrow Microenvironment—The Involvement Of Extracellular Nucleotides And Purinergic Signaling, Mariusz Z. Ratajczak, Mateusz Adamiak, Monika Plonka, Ahmed Abdel-Latif, Janina Ratajczak

Internal Medicine Faculty Publications

Hematopoietic stem/progenitor cells (HSPCs) circulate in peripheral blood (PB) under normal conditions and their number increases in response to stress, inflammation, tissue/organ injury, and may increase up to 100-fold after administration of mobilization-inducing drugs. Mounting evidence suggests that mobilizing agent-induced mobilization of HSPCs from bone marrow into PB is a result of innate immunity-mediated sterile inflammation in the bone marrow (BM) microenvironment. A critical initiating role in this process is played by tissue/organ injury-mediated or pharmacologically induced release from bone marrow-residing granulocytes and monocytes of (i) danger-associated molecular patterns (DAMPs), (ii) reactive oxygen species (ROS), and (iii) proteolytic and lipolytic …

Outcome Of Patients With Small Vessel Vasculitis After Renal Transplantation: National Database Analysis, Amr El-Husseini, Sherif Saleh, Omer Hamad, Xiaonan Mei, Ana L. Castellanos, Daniel L. Davenport, Roberto Gedaly, B. Peter Sawaya

Internal Medicine Faculty Publications

Background. Small vessel vasculitis commonly affects the kidney and can progress to end-stage renal disease. The goal of this study is to compare outcomes of patients who received a renal transplant as a result of small vessel vasculitis (group A) with those who received kidney transplants because of other causes (group B). Methods. This is a retrospective analysis of United Network for Organ Sharing registry data for adult primary kidney transplants from January 2000 to December 2014. Group A patients (N = 2196) were compared with a group B (N = 6588); groups were case matched for age, race, sex, …

Telotristat Ethyl In Carcinoid Syndrome: Safety And Efficacy In The Telecast Phase 3 Trial, Marianne Pavel, David J. Gross, Marta Benavent, Petros Perros, Raj Srirajaskanthan, Richard R. P. Warner, Matthew H. Kulke, Lowell B. Anthony, Pamela L. Kunz, Dieter Hörsch, Martin O Weickert, Pablo Lapuerta, Wenjun Jiang, Kenneth Kassler-Taub, Suman Wason, Rosanna Fleming, Douglas Fleming, Rocio Garcia-Carbonero

Internal Medicine Faculty Publications

Telotristat ethyl, a tryptophan hydroxylase inhibitor, was efficacious and well tolerated in the phase 3 TELESTAR study in patients with carcinoid syndrome (CS) experiencing ≥ 4 bowel movements per day (BMs/day) while on somatostatin analogs (SSAs). TELECAST, a phase 3 companion study, assessed the safety and efficacy of telotristat ethyl in patients with CS (diarrhea, flushing, abdominal pain, nausea or elevated urinary 5-hydroxyindoleacetic acid (u5-HIAA)) with < 4 BMs/day on SSAs (or ≥ 1 symptom or ≥ 4 BMs/day if not on SSAs) during a 12-week double-blind treatment period followed by a 36-week open-label extension (OLE). The primary safety and efficacy endpoints were incidence of treatment-emergent adverse events (TEAEs) and percent change from baseline in 24-h u5-HIAA at week 12. Patients (N = 76) were randomly assigned (1:1:1) to receive placebo or telotristat ethyl 250 mg or 500 mg 3 times per day (tid); 67 continued receiving telotristat ethyl 500 mg tid during the OLE. …

Delayed Sternal Closure Does Not Reduce Complications Associated With Coagulopathy And Right Ventricular Failure After Left Ventricular Assist Device Implantation, Roh Yanagida, Navin Rajagopalan, Daniel L. Davenport, Thomas A. Tribble, Mark A. Bradley, Charles W. Hoopes

Internal Medicine Faculty Publications

Delayed sternal closure (DSC) is occasionally adopted after implantation of left ventricular assist device (LVAD). Recent studies suggest that DSC be used for high risk group of patients with coagulopathy, hemodynamic instability or right ventricular failure. However, whether DSC is efficacious for bleeding complication or right ventricular failure is not known. This study is single center analysis of 52 patients, who underwent LVAD implantation. Of those 52 patients, 40 consecutive patients underwent DSC routinely. The sternum was left open with vacuum assist device after implantation of LVAD. Perioperative outcome of the patients who underwent routine DSC were compared with 12 …

Central Nervous System Histoplasmosis: Multicenter Retrospective Study On Clinical Features, Diagnostic Approach And Outcome Of Treatment, Joseph Wheat, Thein Myint, Ying Guo, Phebe Kemmer, Chadi A. Hage, Colin Terry, Marwan M. Azar, James Riddell, Peter Ender, Sharon Chen, Kareem Shehab, Kerry Cleveland, Eden Esguerra, James Johnson, Patty Wright, Vanja Douglas, Pascalis Vergidis, Winnie Ooi, John Baddley, David Bamberger, Raed N. Khairy, Holenarasipur R. Vikram, Elizabeth Jenny-Avital, Geetha Sivasubramanian, Karen Bowlware, Barbara Pahud, Juan Sarria, Townson Tsai, Maha Assi, Satish Mocherla

Internal Medicine Faculty Publications

Central nervous system (CNS) involvement occurs in 5 to 10% of individuals with disseminated histoplasmosis. Most experience has been derived from small single center case series, or case report literature reviews. Therefore, a larger study of central nervous system (CNS) histoplasmosis is needed in order to guide the approach to diagnosis, and treatment.

A convenience sample of 77 patients with histoplasmosis infection of the CNS was evaluated. Data was collected that focused on recognition of infection, diagnostic techniques, and outcomes of treatment.

Twenty nine percent of patients were not immunosuppressed. Histoplasma antigen, or anti-Histoplasma antibodies were detected in the …

Global Survey Of Clinical Oncology Workforce, Aju Mathew

Internal Medicine Faculty Publications

A lack of well-trained clinical oncologists can result in significant cancer health disparities. The magnitude of this problem around the world is poorly described in the literature. A comprehensive global survey of the clinical oncology workforce was conducted. Data on the number of clinical oncologists in 93 countries were obtained from 30 references. The mortality-to-incidence ratio was estimated by using data on incidence and mortality rates from the GLOBOCAN 2012 database; the ratio was > 70% in 26 countries (28%), which included 21 countries in Africa (66%) and five countries in Asia (26%). Eight countries had no clinical oncologist available to …

Effects Of Six Common Dietary Nutrients On Murine Intestinal Organoid Growth, Tenson Cai, Yijun Qi, Albert Jergens, Michael Wannemuehler, Terrence A. Barrett, Qun Wang

Internal Medicine Faculty Publications

The intestinal epithelium of the gastrointestinal (GI) tract constantly renews itself to absorb nutrients and provide protection for the body from the outside world. Since the intestinal epithelium is constantly exposed to various chemicals and dietary components, it is critical to determine which constituents promote or inhibit intestinal epithelium health and growth rate. Intestinal organoids, three-dimensional miniature models of the intestines, represent an ex vivo tool to investigate intestinal physiology and growth patterns. In this study, we measured the growth rates of murine intestinal organoids exposed to various concentrations of different dietary constituents. Results indicate that caffeic acid inhibited organoid …

Beta-Catenin Cleavage Enhances Transcriptional Activation, Tatiana Goretsky, Emily M. Bradford, Qing Ye, Olivia F. Lamping, Tomas Vanagunas, Mary Pat Moyer, Patrick C. Keller, Preetika Sinh, Josep M. Llovet, Tianyan Gao, Qing-Bai She, Linheng Li, Terrence A. Barrett

Internal Medicine Faculty Publications

Nuclear activation of Wnt/β-catenin signaling is required for cell proliferation in inflammation and cancer. Studies from our group indicate that β-catenin activation in colitis and colorectal cancer (CRC) correlates with increased nuclear levels of β-catenin phosphorylated at serine 552 (pβ-Cat⁵⁵²). Biochemical analysis of nuclear extracts from cancer biopsies revealed the existence of low molecular weight (LMW) pβ-Cat⁵⁵², increased to the exclusion of full size (FS) forms of β-catenin. LMW β-catenin lacks both termini, leaving residues in the armadillo repeat intact. Further experiments showed that TCF4 predominantly binds LMW pβ-Cat⁵⁵² in the nucleus of inflamed and …

A Plasma Telomeric Cell-Free Dna Level In Unaffected Women With Brca1 Or/And Brca2 Mutations: A Pilot Study, Shatovisha Dey, Natascia Marino, Kanokwan Bishop, Paige N. Dahlgren, Aditi Shendre, Anna Maria Storniolo, Chunyan He, Hiromi Tanaka

Internal Medicine Faculty Publications

Plasma cell-free DNA (cfDNA) is a small DNA fragment circulating in the bloodstream originating from both non-tumor- and tumor-derived cells. A previous study showed that a plasma telomeric cfDNA level decreases in sporadic breast cancer patients compared to controls. Tumor suppressor gene products including BRCA1 and BRCA2 (BRCA1&2) play an important role in telomere maintenance. In this study, we hypothesized that the plasma telomeric cfDNA level is associated with the mutation status of BRCA1&2 genes. To test this hypothesis, we performed plasma telomeric cfDNA quantitative PCR (qPCR)-based assays to compare 28 women carriers of the BRCA1&2 mutation with age-matched controls …