Medical Specialties Commons^™

Multisite Evaluation Of The Bd Max Extended Enteric Bacterial Panel For Detection Of Yersinia Enterocolitica, Enterotoxigenic Escherichia Coli, Vibrio, And Plesiomonas Shigelloides From Stool Specimens., Patricia J Simner, Margret Oethinger, Kathleen A Stellrecht, Dylan R Pillai, Ram Yogev, Helene Leblond, Joel Mortensen

Articles, Abstracts, and Reports

The purpose of this study was to perform a multisite evaluation to establish the performance characteristics of the BD Max extended enteric bacterial panel (xEBP) assay directly from unpreserved or Cary-Blair-preserved stool specimens for the detection of Yersinia enterocolitica, enterotoxigenic Escherichia coli (ETEC), Vibrio, and Plesiomonas shigelloides The study included prospective, retrospective, and prepared contrived specimens from 6 clinical sites. BD Max xEBP results were compared to the reference method, which included standard culture techniques coupled with alternate PCR and sequencing, except for ETEC, for which the reference method was two alternate PCRs and sequencing. Alternate PCR was …

Linking Tuberous Sclerosis Complex, Excessive Mtor Signaling, And Age-Related Neurodegeneration: A New Association Between Tsc1 Mutation And Frontotemporal Dementia, Nicholas T. Olney, Carolina Alquezar, Eliana Marisa Ramos, Alissa L. Nana, Jamie C. Fong, Anna M. Karydas, Joanne B Taylor, Melanie L. Stephens, Andrea R. Argouarch, Victoria A. Van Berlo, Deepika R. Dokuru, Elliott H. Sherr, Gregory A. Jicha, William P. Dillon, Rahul S. Desikan, Mary De May, William W. Seeley, Giovanni Coppola, Bruce L. Miller, Aimee W. Kao

Neurology Faculty Publications

No abstract provided.

Understanding The Patient Experience With Carcinoid Syndrome: Exit Interviews From A Randomized, Placebo-Controlled Study Of Telotristat Ethyl, Lowell B. Anthony, Claire Ervin, Pablo Lapuerta, Matthew H. Kulke, Pamela Kunz, Emily Bergsland, Dieter Hörsch, David C. Metz, Janice Pasieka, Nick Pavlakis, Marianne Pavel, Martyn Caplin, Kjell Öberg, John Ramage, Emily Evans, Qi Melissa Yang, Shanna Jackson, Karie Arnold, Linda Law, Dana B. Dibenedetti

Markey Cancer Center Faculty Publications

Purpose: Telotristat ethyl, an oral tryptophan hydroxylase inhibitor, is intended to treat carcinoid syndrome by reducing serotonin production. Telotristat ethyl was evaluated in TELESTAR, a Phase III study for patients who had carcinoid syndrome with at least 4 bowel movements (BMs) per day and who were receiving somatostatin analogue therapy. This interview substudy was conducted to provide insight into the patient experience in TELESTAR and to help understand whether reductions in BM frequency (the primary end point) and other symptoms were clinically meaningful.

Methods: Participating sites were asked to invite (before randomization) all eligible patients to telephone interviews scheduled at …

Pro-Inflammatory Chemokines And Cytokines Dominate The Blister Fluid Molecular Signature In Patients With Epidermolysis Bullosa And Affect Leukocyte And Stem Cell Migration., Vitali Alexeev, Julio Cesar Salas-Alanis, Francis Palisson, Lila Mukhtarzada, Giulio Fortuna, Jouni Uitto, Andrew P. South, Olga Igoucheva

Department of Dermatology and Cutaneous Biology Faculty Papers

Hereditary epidermolysis bullosa (EB) is associated with skin blistering and the development of chronic nonhealing wounds. Although clinical studies have shown that cell-based therapies improve wound healing, the recruitment of therapeutic cells to blistering skin and to more advanced skin lesions remains a challenge. Here, we analyzed cytokines and chemokines in blister fluids of patients affected by dystrophic, junctional, and simplex EB. Our analysis revealed high levels of CXCR1, CXCR2, CCR2, and CCR4 ligands, particularly dominant in dystrophic and junctional EB. In vitro migration assays demonstrated the preferential recruitment of CCR4⁺ lymphocytes and CXCR1⁺, CXCR2⁺, …

Bimodal Coupling Of Ripples And Slower Oscillations During Sleep In Patients With Focal Epilepsy., Inkyung Song, Iren Orosz, Inna Chervoneva, Zachary J. Waldman, Itzhak Fried, Chengyuan Wu, Ashwini Sharan, Noriko Salamon, Richard Gorniak, Sandra Dewar, Anatol Bragin, Jerome Engel, Michael R. Sperling, Richard Staba, Shennan A. Weiss

Department of Neurology Faculty Papers

OBJECTIVE: Differentiating pathologic and physiologic high-frequency oscillations (HFOs) is challenging. In patients with focal epilepsy, HFOs occur during the transitional periods between the up and down state of slow waves. The preferred phase angles of this form of phase-event amplitude coupling are bimodally distributed, and the ripples (80-150 Hz) that occur during the up-down transition more often occur in the seizure-onset zone (SOZ). We investigated if bimodal ripple coupling was also evident for faster sleep oscillations, and could identify the SOZ.

METHODS: Using an automated ripple detector, we identified ripple events in 40-60 min intracranial electroencephalography (iEEG) recordings from 23 …

Endothelial Cell-Derived Microparticles From Patients With Obstructive Sleep Apnea Hypoxia Syndrome And Coronary Artery Disease Increase Aortic Endothelial Cell Dysfunction., Lixin Jia, Jingyao Fan, Wei Cui, Sa Liu, Na Li, Wayne Bond Lau, Xin-Liang Ma, Jie Du, Shaoping Nie, Yongxiang Wei

Department of Emergency Medicine Faculty Papers

BACKGROUND/AIMS: Obstructive sleep apnea hypoxia syndrome (OSAHS) is an independent risk factor for coronary artery disease (CAD). Treatment of OSAHS improves clinical outcome in some CAD patients, but the relationship between OSAHS and CAD is complex. Microparticles (MPs) are shed by the plasma membrane by either physiologic or pathologic stimulation. In the current study, we investigated the role of MPs in the context of OSAHS.

METHODS AND RESULTS: 54 patients with both suspected coronary artery stenosis and OSAHS were recruited and underwent both coronary arteriography and polysomnography. Circulating MPs were isolated and analyzed by flow cytometry. CAD+OSAHS patients exhibited greater …

Outlier Identification In Radiation Therapy Knowledge-Based Planning: A Study Of Pelvic Cases., Yang Sheng, Yaorong Ge, Lulin Yuan, Taoran Li, Fang-Fang Yin, Qingrong Jackie Wu

Department of Radiation Oncology Faculty Papers

PURPOSE: The purpose of this study was to apply statistical metrics to identify outliers and to investigate the impact of outliers on knowledge-based planning in radiation therapy of pelvic cases. We also aimed to develop a systematic workflow for identifying and analyzing geometric and dosimetric outliers.

METHODS: Four groups (G1-G4) of pelvic plans were sampled in this study. These include the following three groups of clinical IMRT cases: G1 (37 prostate cases), G2 (37 prostate plus lymph node cases) and G3 (37 prostate bed cases). Cases in G4 were planned in accordance with dynamic-arc radiation therapy procedure and include 10 …

A Nationwide Study On The Prevalence Of Functional Gastrointestinal Disorders In School-Children., Miguel Saps, Jairo Enrique Moreno-Gomez, Carmen Rossy Ramírez-Hernández, John M. Rosen, C A. Velasco-Benitez

Manuscripts, Articles, Book Chapters and Other Papers

Introduction: Functional gastrointestinal disorders (FGIDs) are highly prevalent worldwide and are thought to result from the interplay of multiple factors that can vary from region to region. Nationwide studies can help understand the regional epidemiology and the pathogenesis of FGIDs. The objectives of this study were to determine the prevalence of FGIDs in school-children of Colombia and assess associated factors.

Methods: A cross-sectional study was carried out at twelve private and public schools in ten cities distributed through the four main geographic regions of Colombia. School-children completed a validated questionnaire to assess functional gastrointestinal disorders according to Rome III criteria. …

Diabetes Conflict Outstrips The Positive Impact Of Self-Efficacy On Youth Adherence And Glycemic Control In Type 1 Diabetes., Amy E. Noser, Lindsay Huffhines, Mark A. Clements, Susana R. Patton

Manuscripts, Articles, Book Chapters and Other Papers

Objective: To examine whether self-efficacy buffers the deleterious consequences of diabetes-specific family conflict on self-monitoring blood glucose (SMBG) and glycated hemoglobin (HbA1c) in youth with type 1 diabetes mellitus (T1DM).

Methods: A total of 129 youth with T1DM (aged 10-16 years) completed measures of diabetes-specific family conflict and self-efficacy for diabetes management, and their blood glucose meter data and HbA1c were extracted from the electronic medical record. We preformed moderation analyses to examine whether self-efficacy moderated the association that diabetes-specific family conflict had with SMBG and HbA1c. We used simple slopes analyses to probe significant interactions.

Results: Our results indicated …

Vitamin D, Heidi D Moretti, Vincent J Colucci, Bradley D Berry

Articles, Abstracts, and Reports

BACKGROUND: Vitamin D status may influence heart failure (HF) patient outcomes by affecting b-type natriuretic peptide (BNP), parathyroid hormone (PTH), and enhancing cardiac contractility. Vitamin D deficiency is associated with morbidity and mortality in HF patients. The objective of this study was to determine if vitamin D3 at a comparatively high dose would replete 25-hydroxyvitamin D (25(OH)D) stores, improve BNP, PTH, cardiopulmonary function, reduce inflammatory markers, and improve quality of life (QOL) in HF patients.

METHODS: This was a 6 month, parallel group, double-blind, placebo-controlled, single clinic center, randomized trial of supplemental vitamin D3 using a dose of 10,000 IU …

Ufm1 Founder Mutation In The Roma Population Causes Recessive Variant Of H-Abc., Eline M C Hamilton, Enrico Bertini, Luba Kalaydjieva, Bharti Morar, Dana Dojčáková, Adeline Vanderver, Recessive H-Abc Research Group.

Neurology Faculty Publications

OBJECTIVE: To identify the gene defect in patients with hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) who are negative for TUBB4A mutations.

METHODS: We performed homozygosity mapping and whole exome sequencing (WES) to detect the disease-causing variant. We used a Taqman assay for population screening. We developed a luciferase reporter construct to investigate the effect of the promoter mutation on expression.

RESULTS: Sixteen patients from 14 families from different countries fulfilling the MRI criteria for H-ABC exhibited a similar, severe clinical phenotype, including lack of development and a severe epileptic encephalopathy. The majority of patients had a …

Association Of Metabolic Syndrome And Change In Unified Parkinson's Disease Rating Scale Scores., Maureen Leehey, Sheng Luo, Saloni Sharma, Anne-Marie A. Wills, Jacquelyn L. Bainbridge, Pei Shieen Wong, David K. Simon, Jay S Schneider, Yunxi Zhang, Adriana Pérez, Rohit Dhall, Chadwick W. Christine, Carlos Singer, Franca Cambi, James T Boyd

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

OBJECTIVE: To explore the association between metabolic syndrome and the Unified Parkinson's Disease Rating Scale (UPDRS) scores and, secondarily, the Symbol Digit Modalities Test (SDMT).

METHODS: This is a secondary analysis of data from 1,022 of 1,741 participants of the National Institute of Neurological Disorders and Stroke Exploratory Clinical Trials in Parkinson Disease Long-Term Study 1, a randomized, placebo-controlled trial of creatine. Participants were categorized as having or not having metabolic syndrome on the basis of modified criteria from the National Cholesterol Education Program Adult Treatment Panel III. Those who had the same metabolic syndrome status at consecutive annual visits …

Intravesical Rad-Ifnα/Syn3 For Patients With High-Grade, Bacillus Calmette-Guerin-Refractory Or Relapsed Non-Muscle-Invasive Bladder Cancer: A Phase Ii Randomized Study., Neal D Shore, Stephen A Boorjian, Daniel J Canter, Kenneth Ogan, Lawrence I Karsh, Tracy M Downs, Leonard G Gomella, Ashish M Kamat, Yair Lotan, Robert S Svatek, Trinity J Bivalacqua, Robert L Grubb, Tracey L Krupski, Seth P Lerner, Michael E Woods, Brant A Inman, Matthew I Milowsky, Alan Boyd, F Peter Treasure, Gillian Gregory, David G Sawutz, Seppo Yla-Herttuala, Nigel R Parker, Colin P N Dinney

Department of Medicine Faculty Papers

Purpose Many patients with high-risk non-muscle-invasive bladder cancer (NMIBC) are either refractory to bacillus Calmette-Guerin (BCG) treatment or may experience disease relapse. We assessed the efficacy and safety of recombinant adenovirus interferon alfa with Syn3 (rAd-IFNα/Syn3), a replication-deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG-refractory or relapsed NMIBC. Methods In this open-label, multicenter (n = 13), parallel-arm, phase II study ( ClinicalTrials.gov identifier: NCT01687244), 43 patients with HG BCG-refractory or relapsed NMIBC received intravesical rAd-IFNα/Syn3 (randomly assigned 1:1 to 1 × 10(11) viral particles (vp)/mL or 3 × 10(11) vp/mL). Patients who responded at months 3, …

Characterization Of Pulmonary Metastases In Children With Hepatoblastoma Treated On Children's Oncology Group Protocol Ahep0731 (The Treatment Of Children With All Stages Of Hepatoblastoma): A Report From The Children's Oncology Group., Allison F. O'Neill, Alexander J. Towbin, Mark D. Krailo, Caihong Xia, Yun Gao, M. Beth Mccarville, Rebecka L. Meyers, Eugene D. Mcgahren, Greg M. Tiao, Stephen P. Dunn, Max R. Langham, Christopher B. Weldon, Milton J. Finegold, Sarangarajan Ranganathan, Wayne L. Furman, Marcio Malogolowkin, Carlos Rodriguez-Galindo, Howard M. Katzenstein

Department of Pediatrics Faculty Papers

Purpose To determine whether the pattern of lung nodules in children with metastatic hepatoblastoma (HB) correlates with outcome. Methods Thirty-two patients with metastatic HB were enrolled on Children's Oncology Group Protocol AHEP0731 and treated with vincristine and irinotecan (VI). Responders to VI received two additional cycles of VI intermixed with six cycles of cisplatin/fluorouracil/vincristine/doxorubicin (C5VD), and nonresponders received six cycles of C5VD alone. Patients were imaged after every two cycles and at the conclusion of therapy. All computed tomography scans and pathology reports were centrally reviewed, and information was collected regarding lung nodule number, size, laterality, timing of resolution, and …

Tnf-Α Promotes Nuclear Enrichment Of The Transcription Factor Tonebp/Nfat5 To Selectively Control Inflammatory But Not Osmoregulatory Responses In Nucleus Pulposus Cells., Zariel I. Johnson, Alexandra C. Doolittle, Joseph W. Snuggs, Irving M. Shapiro, Christine L. Le Maitre, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

Intervertebral disc degeneration (IDD) causes chronic back pain and is linked to production of proinflammatory molecules by nucleus pulposus (NP) and other disc cells. Activation of tonicity-responsive enhancer-binding protein (TonEBP)/NFAT5 by non-osmotic stimuli, including proinflammatory molecules, occurs in cells involved in immune response. However, whether inflammatory stimuli activate TonEBP in NP cells and whether TonEBP controls inflammation during IDD is unknown. We show that TNF-α, but not IL-1β or LPS, promoted nuclear enrichment of TonEBP protein. However, TNF-α-mediated activation of TonEBP did not cause induction of osmoregulatory genes. RNA sequencing showed that 8.5% of TNF-α transcriptional responses were TonEBP-dependent and …

Effect Of Oral Semaglutide Compared With Placebo And Subcutaneous Semaglutide On Glycemic Control In Patients With Type 2 Diabetes: A Randomized Clinical Trial., Melanie Davies, Thomas R. Pieber, Marie-Louise Hartoft-Nielsen, Oluf K.H. Hansen, Serge Jabbour, Julio Rosenstock

Department of Medicine Faculty Papers

Importance: Glucagon-like peptide-1 (GLP-1) receptor agonists are effective therapies for the treatment of type 2 diabetes and are all currently available as an injection.

Objectives: To compare the effects of oral semaglutide with placebo (primary) and open-label subcutaneous semaglutide (secondary) on glycemic control in patients with type 2 diabetes.

Design, Setting, and Patients: Phase 2, randomized, parallel-group, dosage-finding, 26-week trial with 5-week follow-up at 100 sites (hospital clinics, general practices, and clinical research centers) in 14 countries conducted between December 2013 and December 2014. Of 1106 participants assessed, 632 with type 2 diabetes and insufficient glycemic control using diet and …

Detection Of Activating Estrogen Receptor Gene (Esr1) Mutations In Single Circulating Tumor Cells, Carmela Paolillo, Zhaomei Mu, Giovanna Rossi, Matthew J. Schiewer, Thomas Nguyen, Laura Austin, Ettore Capoluongo, Karen E. Knudsen, Massimo Cristofanilli, Paolo Fortina

Department of Cancer Biology Faculty Papers

Purpose: Early detection is essential for treatment plans before onset of metastatic disease. Our purpose was to demonstrate feasibility to detect and monitor estrogen receptor 1 (ESR1) gene mutations at the single circulating tumor cell (CTC) level in metastatic breast cancer (MBC). Experimental Design: We used a CTC molecular characterization approach to investigate heterogeneity of 14 hotspot mutations in ESR1 and their correlation with endocrine resistance. Combining the CellSearch and DEPArray technologies allowed recovery of 71 single CTCs and 12 WBC from 3 ER-positive MBC patients. Forty CTCs and 12 WBC were subjected to whole genome amplification by MALBAC and …

A Two-Biomarker Model Predicts Mortality In The Critically Ill With Sepsis., Carmen Mikacenic, Brenda L Price, Susanna Harju-Baker, D Shane O'Mahony, Cassianne Robinson-Cohen, Frank Radella, William O Hahn, Ronit Katz, David C Christiani, Jonathan Himmelfarb, W Conrad Liles, Mark M Wurfel

Articles, Abstracts, and Reports

RATIONALE: Improving the prospective identification of patients with systemic inflammatory response syndrome (SIRS) and sepsis at low risk for organ dysfunction and death is a major clinical challenge.

OBJECTIVES: To develop and validate a multibiomarker-based prediction model for 28-day mortality in critically ill patients with SIRS and sepsis.

METHODS: A derivation cohort (n = 888) and internal test cohort (n = 278) were taken from a prospective study of critically ill intensive care unit (ICU) patients meeting two of four SIRS criteria at an academic medical center for whom plasma was obtained within 24 hours. The validation cohort (n = …

Oral Morphine Versus Ibuprofen Administered At Home For Postoperative Orthopedic Pain In Children: A Randomized Controlled Trial, Naveen Poonai, Natasha Datoo, Samina Ali, Megan Cashin, Amy L Drendel, Rongbo Zhu, Natasha Lepore, Michael Greff, Michael Rieder, Debra Bartley

Paediatrics Publications

BACKGROUND: Oral morphine for postoperative pain after minor pediatric surgery, while increasingly popular, is not supported by evidence. We evaluated whether oral morphine was superior to ibuprofen for at-home management of children's postoperative pain.

METHODS: We conducted a randomized superiority trial comparing oral morphine (0.5 mg/kg) with ibuprofen (10 mg/kg) in children 5 to 17 years of age who had undergone minor outpatient orthopedic surgery (June 2013 to September 2016). Participants took up to 8 doses of the intervention drug every 6 hours as needed for pain at home. The primary outcome was pain, according to the Faces Pain Scale …

Circulating Early- And Mid-Pregnancy Micrornas And Risk Of Gestational Diabetes., Pandora L Wander, Edward J Boyko, Karin Hevner, Viraj J Parikh, Mahlet G Tadesse, Tanya K Sorensen, Michelle A Williams, Daniel A Enquobahrie

Articles, Abstracts, and Reports

AIMS: Epigenetic regulators, including microRNAs (miRNAs), are implicated in type 2 diabetes, but evidence linking circulating miRNAs in pregnancy and risk of gestational diabetes (GDM) is sparse. Potential modifiers, including pre-pregnancy overweight/obesity and offspring sex, are unexamined. We hypothesized that circulating levels of early-mid-pregnancy (range 7-23weeks of gestation) candidate miRNAs are related to subsequent development of GDM. We also hypothesized that miRNA-GDM associations might vary by pre-pregnancy body-mass index (ppBMI) or offspring sex.

METHODS: In a case-control analysis (36GDM cases/80 controls) from the Omega study, a prospective cohort study of pregnancy complications, we measured early-mid-pregnancy plasma levels of 10miRNAs chosen …

Exosomal Microrna For Detection Of Cardiac Sarcoidosis., Elliott D Crouser, Nabeel Y Hamzeh, Lisa A Maier, Mark W Julian, May Gillespie, Mohammad Rahman, David Baxter, Xiaogang Wu, S Patrick Nana-Sinkam, Kai Wang

Articles, Abstracts, and Reports

No abstract provided.

Neurological Improvement Of Perineural And Leptomeningeal Spread Of Squamous Cell Carcinoma Treated With Intrathecal Chemotherapy And Systemic Egfr Inhibition., Vincent Alexander Van Vugt, Marlon Garzo Saria, Andres Javier, Navin Kesari, Tiffany Turpin, Santosh Kesari

Articles, Abstracts, and Reports

Squamous cell carcinoma (SCC) is a common cancer of the skin. Risk factors include fair skin, excessive sun and ultraviolet light exposure, and history of xeroderma pigmentosa. Perineural invasion (PNI), an uncommon manifestation of SCC, involves microscopic tumor cells invading various layers of the nerve sheath. It is associated with a poorer prognosis. Standard treatment for PNI includes radiation therapy. Here, we describe a case an older gentleman with a history of SCC with PNI successfully treated with erlotinib and intrathecal chemotherapy.

Clinically Silent Alzheimer's And Vascular Pathologies Influence Brain Networks Supporting Executive Function In Healthy Older Adults, Brian T. Gold, Christopher A. Brown, Jonathan G. Hakun, Leslie M. Shaw, John Q. Trojanowski, Charles D. Smith

Neuroscience Faculty Publications

Aging is associated with declines in executive function. We examined how executive functional brain systems are influenced by clinically silent Alzheimer’s disease (AD) pathology and cerebral white matter hyperintensities (WMHs). Twenty-nine younger adults and thirty-four cognitively normal older adults completed a working memory paradigm while functional magnetic resonance imaging (fMRI) was performed. Older adults further underwent lumbar cerebrospinal fluid (CSF) draw for assessment of AD pathology and FLAIR imaging for assessment of WMHs. Accurate working memory performance in both age groups was associated with high fronto-visual functional connectivity (fC). However, in older adults, higher expression of fronto-visual fC was linked …

Hypothermic Cooling Measured By Thermal Magnetic Resonance Imaging; Feasibility And Implications For Virtual Imaging In The Urogenital Pelvis., Douglas Skarecky, Hon Yu, Jennifer Linehan, Blanca Morales, Min-Ying Su, Peter Fwu, Thomas Ahlering

Articles, Abstracts, and Reports

OBJECTIVE: To study the combination of thermal magnetic resonance imaging (MRI) and novel hypothermic cooling, via an endorectal cooling balloon (ECB), to assess the effective dispersion and temperature drop in pelvic tissue to potentially reduce inflammatory cascade in surgical applications.

METHODS: Three male subjects, before undergoing robot-assisted radical prostatectomy, were cooled via an ECB, rendered MRI compatible for patient safety before ECB hypothermia. MRI studies were performed using a 3T scanner and included T2-weighted anatomic scan for the pelvic structures, followed by a temperature mapping scan. The sequence was performed repeatedly during the cooling experiment, whereas the phase data were …

Secondhand Smoke Exposure And Preclinical Markers Of Cardiovascular Risk In Toddlers, Judith A Groner, Hong Huang, Mandar S. Joshi, Nicholas Eastman, Lisa Nicholson, John Anthony Bauer

Pediatrics Faculty Publications

Objective: Links between secondhand smoke (SHS) exposure and cardiovascular disease in adults are well established but seldom reported during childhood. Although rates of smoking have decreased, young children from low-income backgrounds remain likely to be exposed to SHS. The purpose of this study was to investigate relationships between SHS exposure in young children and several preclinical markers of cardiovascular risk that have been established as relevant to adult populations.

Methods: 139 children, 2–5 years of age, were enrolled in a cross-sectional study. SHS exposure was objectively determined by hair nicotine level; a comprehensive panel of clinical markers (AM blood pressure, …

Phase 1b Trial Of Proteasome Inhibitor Carfilzomib With Irinotecan In Lung Cancer And Other Irinotecan-Sensitive Malignancies That Have Progressed On Prior Therapy (Onyx Ist Reference Number: Car-Ist-553)., Susanne M Arnold, Kari Chansky, Markos Leggas, Michael A Thompson, John L Villano, John Hamm, Rachel E Sanborn, Glen J Weiss, Gurkamal Chatta, Maria Q Baggstrom

Articles, Abstracts, and Reports

Introduction Proteasome inhibition is an established therapy for many malignancies. Carfilzomib, a novel proteasome inhibitor, was combined with irinotecan to provide a synergistic approach in relapsed, irinotecan-sensitive cancers. Materials and Methods Patients with relapsed irinotecan-sensitive cancers received carfilzomib (Day 1, 2, 8, 9, 15, and 16) at three dose levels (20/27 mg/m2, 20/36 mg/m2 and 20/45 mg/m2/day) in combination with irinotecan (Days 1, 8 and 15) at 125 mg/m2/day. Key eligibility criteria included measurable disease, a Zubrod PS of 0 or 1, and acceptable organ function. Patients with stable asymptomatic brain metastases were eligible. Dose escalation utilized a standard 3 …

Randomized Phase Ii Study Comparing Prophylactic Cranial Irradiation Alone To Prophylactic Cranial Irradiation And Consolidative Extracranial Irradiation For Extensive-Disease Small Cell Lung Cancer (Ed Sclc): Nrg Oncology Rtog 0937, Elizabeth M. Gore, Chen Hu, Alexander Y. Sun, Daniel F. Grimm, Suresh S. Ramalingam, Neal E. Dunlap, Kristin A. Higgins, Maria Werner-Wasik, Aaron M. Allen, Puneeth Iyengar, Gregory M. M. Videtic, Russell K. Hales, Ronald C. Mcgarry, James J. Urbanic, Anthony T. Pu, Candice A. Johnstone, Volker W. Stieber, Rebecca Paulus, Jeffrey D. Bradley

Radiation Medicine Faculty Publications

Introduction—RTOG-0937 is a randomized phase-II trial evaluating 1-year OS with PCI or PCI plus consolidative radiation therapy (cRT) to intra-thoracic disease and extracranial metastases for ED-SCLC.

Methods—Patients with 1–4 extracranial metastases were eligible after CR or PR to chemotherapy. Randomization was to PCI or PCI+cRT to the thorax and metastases. Original stratification included PR vs CR after chemotherapy and 1 vs 2–4 metastases; age < 65 vs ≥ 65 was added after an observed imbalance. PCI was 25GY/10 fractions. cRT was 45GY/15 fractions. To detect an OS improvement from 30% to 45% with a 34% hazard reduction (HR=0·66) under a 0.1 type-1 error (1-sided) and 80% power, 154 patients were required.

Results—Ninety-seven patients were randomized between March, 2010 and February, 2015. Eleven patients were ineligible (nine PCI, two PCI+cRT), leaving 42 randomized to PCI and 44 to PCI+cRT. At planned interim analysis the study …

Impact Of Superstorm Sandy On Medicare Patients' Utilization Of Hospitals And Emergency Departments., Benoit Stryckman, Lauren Walsh, Brendan G. Carr, Nathaniel Hupert, Nicole Lurie

Department of Emergency Medicine Faculty Papers

INTRODUCTION: National health security requires that healthcare facilities be prepared to provide rapid, effective emergency and trauma care to all patients affected by a catastrophic event. We sought to quantify changes in healthcare utilization patterns for an at-risk Medicare population before, during, and after Superstorm Sandy's 2012 landfall in New Jersey (NJ).

METHODS: This study is a retrospective cohort study of Medicare beneficiaries impacted by Superstorm Sandy. We compared hospital emergency department (ED) and healthcare facility inpatient utilization in the weeks before and after Superstorm Sandy landfall using a 20% random sample of Medicare fee-for-service beneficiaries continuously enrolled in 2011 …

Acute Treatment With Doxorubicin Affects Glutamate Neurotransmission In The Mouse Frontal Cortex And Hippocampus, Theresa Currier Thomas, Joshua A. Beitchman, Francois Pomerleau, Teresa Noel, Paiboon Jungsuwadee, D. Allan Butterfield, Daret K. St. Clair, Mary Vore, Greg A. Gerhardt

Spinal Cord and Brain Injury Research Center Faculty Publications

Doxorubicin (DOX) is a potent chemotherapeutic agent known to cause acute and long-term cognitive impairments in cancer patients. Cognitive function is presumed to be primarily mediated by neuronal circuitry in the frontal cortex (FC) and hippocampus, where glutamate is the primary excitatory neurotransmitter. Mice treated with DOX (25 mg/kg i.p.) were subjected to in vivo recordings under urethane anesthesia at 24h post-DOX injection or 5 consecutive days of cognitive testing (Morris Water Maze; MWM). Using novel glutamate-selective microelectrode arrays, amperometric recordings measured parameters of extracellular glutamate clearance and potassium-evoked release of glutamate within the medial FC and dentate gyrus (DG) …

Association Of Disease Location And Treatment With Survival In Diffuse Large B-Cell Lymphoma Of The Eye And Ocular Adnexal Region., Aseef H H. Ahmed, C. Stephen Foster, Carol L. Shields

Wills Eye Hospital Papers

Importance: Primary diffuse large B-cell lymphoma (DLBCL) of the ocular region is rare, and the utility of surgery and radiation therapy remains unresolved.

Objective: To explore the clinical characteristics and determine factors associated with overall survival in primary vitreoretinal lymphoma (PVRL) and ocular adnexal (OA)-uveal DLBCL.

Design, Setting, and Participants: This retrospective analysis included 396 patients with ophthalmic DLBCL from January 1, 1973, through December 31, 2014, using the Surveillance, Epidemiology, and End Results database. The median follow-up was 39.0 months (interquartile range, 5.1-72.9 months). All patients diagnosed with primary DLBCL of the eye or retina (PVRL) or the eyelid, …