Medicine and Health Sciences Commons^™

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

Department of Pharmacology and Experimental Therapeutics Faculty Papers

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

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

Applying Multiple Data Collection Tools To Quantify Human Papillomavirus Vaccine Communication On Twitter., Philip M. Massey, Amy Leader, Elad Yom-Tov, Alexandra Budenz, Kara Fisher, Ann C. Klassen

Department of Medical Oncology Faculty Papers

BACKGROUND: Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. There are several vaccines that protect against strains of HPV most associated with cervical and other cancers. Thus, HPV vaccination has become an important component of adolescent preventive health care. As media evolves, more information about HPV vaccination is shifting to social media platforms such as Twitter. Health information consumed on social media may be especially influential for segments of society such as younger populations, as well as ethnic and racial minorities.

OBJECTIVE: The objectives of our study were to quantify HPV vaccine communication on …

Inter-Rater Reliability Of Post-Arrest Cerebral Performance Category (Cpc) Scores., Anne V. Grossestreuer, Benjamin S. Abella, Kelsey R. Sheak, Marisa J. Cinousis, Sarah M. Perman, Marion Leary, Douglas J. Wiebe, David F. Gaieski

Department of Emergency Medicine Faculty Papers

PURPOSE: Cerebral Performance Category (CPC) scores are often an outcome measure for post-arrest neurologic function, collected worldwide to compare performance, evaluate therapies, and formulate recommendations. At most institutions, no formal training is offered in their determination, potentially leading to misclassification.

MATERIALS AND METHODS: We identified 171 patients at 2 hospitals between 5/10/2005 and 8/31/2012 with two CPC scores at hospital discharge recorded independently - in an in-house quality improvement database and as part of a national registry. Scores were abstracted retrospectively from the same electronic medical record by two separate non-clinical researchers. These scores were compared to assess inter-rater reliability …

The Association Between Hemoglobin Concentration And Neurologic Outcome After Cardiac Arrest., Nicholas J. Johnson, Babette Rosselot, Sarah M. Perman, Kalani Dodampahala, Munish Goyal, David F. Gaieski, Anne V. Grossestreuer

Department of Emergency Medicine Faculty Papers

PURPOSE: The purpose of the study is to determine the association between hemoglobin concentration (Hgb) and neurologic outcome in postarrest patients.

METHODS: We conducted a retrospective cohort study using the Penn Alliance for Therapeutic Hypothermia (PATH) cardiac arrest registry. Inclusion criteria were resuscitated cardiac arrest (inhospital or out of hospital) and an Hgb value recorded within 24 hours of return of spontaneous circulation. The primary outcome was favorable neurologic status at hospital discharge. Survival to hospital discharge was a secondary outcome.

RESULTS: There were 598 eligible patients from 21 hospitals. Patients with favorable neurologic outcome had significantly higher median Hgb …

The 2016 Academic Emergency Medicine Consensus Conference, "Shared Decision Making In The Emergency Department: Development Of A Policy-Relevant Patient-Centered Research Agenda" Diagnostic Testing Breakout Session Report., Tyler W. Barrett, Kristin L. Rising, M. Fernanda Bellolio, M. Kennedy Hall, Aaron Brody, Kenneth W. Dodd, Mira Grieser, Phillip D. Levy, Ali S. Raja, Wesley H. Self, Gail Weingarten, Erik P. Hess, Judd Hollander

Department of Emergency Medicine Faculty Papers

Diagnostic testing is an integral component of patient evaluation in the emergency department (ED). Emergency clinicians frequently use diagnostic testing to more confidently exclude "worst-case" diagnoses rather than to determine the most likely etiology for a presenting complaint. Increased utilization of diagnostic testing has not been associated with reductions in disease-related mortality but has led to increased overall healthcare costs and other unintended consequences (e.g., incidental findings requiring further workup, unnecessary exposure to ionizing radiation or potentially nephrotoxic contrast). Shared decision making (SDM) presents an opportunity for clinicians to discuss the benefits and harms associated with diagnostic testing with patients …

V-Src Oncogene Induces Trop2 Proteolytic Activation Via Cyclin D1., Xiaoming Ju, Xuanmao Jiao, Adam Ertel, Mathew C. Casimiro, Gabriele Disante, Shengqiong Deng, Zhiping Li, Agnese Di Rocco, Tingting Zhan, Adam Hawkins, Tanya Stoyanova, Sebastiano Andò, Alessandro Fatatis, Michael P. Lisanti, Leonard G. Gomella, Lucia R. Languino, Richard G. Pestell

Department of Cancer Biology Faculty Papers

Proteomic analysis of castration-resistant prostate cancer demonstrated the enrichment of Src tyrosine kinase activity in approximately 90% of patients. Src is known to induce cyclin D1, and a cyclin D1-regulated gene expression module predicts poor outcome in human prostate cancer. The tumor-associated calcium signal transducer 2 (TACSTD2/Trop2/M1S1) is enriched in the prostate, promoting prostate stem cell self-renewal upon proteolytic activation via a γ-secretase cleavage complex (PS1, PS2) and TACE (ADAM17), which releases the Trop2 intracellular domain (Trop2 ICD). Herein, v-Src transformation of primary murine prostate epithelial cells increased the proportion of prostate cancer stem cells as characterized by gene expression, …

Differential Item Functioning In The Patient Reported Outcomes Measurement Information System Pediatric Short Forms In A Sample Of Children And Adolescents With Cerebral Palsy., Wendy J. Coster, Pengsheng Ni, Mary D. Slavin, Pamela A. Kisala, Ratna Nandakumar, Mary Jane Mulcahey, David S. Tulsky, Alan M. Jette

Department of Occupational Therapy Faculty Papers

AIM: The present study examined the Patient Reported Outcomes Measurement Information System (PROMIS) Mobility, Fatigue, and Pain Interference Short Forms (SFs) in children and adolescents with cerebral palsy (CP) for the presence of differential item functioning (DIF) relative to the original calibration sample.

METHOD: Using the Graded Response Model we compared item parameter estimates generated from a sample of 303 children and adolescents with CP (175 males, 128 females; mean age 15y 5mo) to parameter estimates from the PROMIS calibration sample, which served as the reference group. DIF was assessed in a two-step process using the item response theory-likelihood ratio-differential …

Duration Of Posttraumatic Amnesia Predicts Neuropsychological And Global Outcome In Complicated Mild Traumatic Brain Injury., Tessa Hart, Thomas A. Novack, Nancy Temkin, Jason Barber, Sureyya S. Dikmen, Ramon Diaz-Arrastia, Joseph Ricker, Dale C. Hesdorffer, Jack Jallo, Nancy H. Hsu, Ross Zafonte

Department of Neurosurgery Faculty Papers

OBJECTIVES: Examine the effects of posttraumatic amnesia (PTA) duration on neuropsychological and global recovery from 1 to 6 months after complicated mild traumatic brain injury (cmTBI).

PARTICIPANTS: A total of 330 persons with cmTBI defined as Glasgow Coma Scale score of 13 to 15 in emergency department, with well-defined abnormalities on neuroimaging.

METHODS: Enrollment within 24 hours of injury with follow-up at 1, 3, and 6 months.

MEASURES: Glasgow Outcome Scale-Extended, California Verbal Learning Test II, and Controlled Oral Word Association Test. Duration of PTA was retrospectively measured with structured interview at 30 days postinjury.

RESULTS: Despite all having a …

Bleeding With Direct Oral Anticoagulants Vs Warfarin: Clinical Experience., John Eikelboom, Geno J. Merli

Department of Surgery Faculty Papers

The risk of bleeding in the setting of anticoagulant therapy continues to be re-evaluated following the introduction of a new generation of direct oral anticoagulants (DOACs). Interruption of DOAC therapy and supportive care may be sufficient for the management of patients who present with mild or moderate bleeding, but in those with life-threatening bleeding, a specific reversal agent is desirable. We review the phase 3 clinical studies of dabigatran, rivaroxaban, apixaban, and edoxaban in patients with nonvalvular atrial fibrillation, in the context of bleeding risk and management.

Should Family Presence Be Allowed During Cardiopulmonary Resuscitation?, Karen J. Brasel, John W. Entwistle Iii, Md, Phd, Robert M. Sade

Department of Surgery Faculty Papers

No abstract provided.

Introduction To Direct Oral Anticoagulants And Rationale For Specific Reversal Agents., Charles V. Pollack

Department of Emergency Medicine Faculty Papers

No abstract provided.

Evidence Supporting Idarucizumab For The Reversal Of Dabigatran., Charles V. Pollack

Department of Emergency Medicine Faculty Papers

Idarucizumab is a monoclonal antibody fragment specifically targeted to dabigatran. It has demonstrated prompt and durable reversal of the anticoagulant effects of dabigatran in animal studies and phase 1 studies of young, elderly, and renally impaired volunteers. Although elective invasive procedures and most bleeding complications in dabigatran-treated patients can be managed by temporarily stopping dabigatran therapy and using supportive measures, there are rare clinical situations that require urgent reversal of the anticoagulant effect of dabigatran. The effectiveness and safety of 5 g of intravenous idarucizumab is being investigated in a prospective, open-label, single-cohort study in patients with serious bleeding or …

Practice Characteristics Of Emergency Department Extracorporeal Cardiopulmonary Resuscitation (Ecpr) Programs In The United States: The Current State Of The Art Of Emergency Department Extracorporeal Membrane Oxygenation (Ed Ecmo)., Joseph E. Tonna, Nicholas J. Johnson, John Greenwood, David F. Gaieski, Zachary Shinar, Joseph M. Bellezo, Lance Becker, Atman P. Shah, Scott T. Youngquist, Michael P. Mallin, James Franklin Fair, Kyle J. Gunnerson, Cindy Weng, Stephen Mckellar

Department of Emergency Medicine Faculty Papers

PURPOSE: To characterize the current scope and practices of centers performing extracorporeal cardiopulmonary resuscitation (eCPR) on the undifferentiated patient with cardiac arrest in the emergency department.

METHODS: We contacted all US centers in January 2016 that had submitted adult eCPR cases to the Extracorporeal Life Support Organization (ELSO) registry and surveyed them, querying for programs that had performed eCPR in the Emergency Department (ED ECMO). Our objective was to characterize the following domains of ED ECMO practice: program characteristics, patient selection, devices and techniques, and personnel.

RESULTS: Among 99 centers queried, 70 responded. Among these, 36 centers performed ED ECMO. …

Post-Transplant Outcomes In High-Risk Compared With Non-High-Risk Multiple Myeloma: A Cibmtr Analysis., Emma C. Scott, Parameswaran Hari, Manish Sharma, Jennifer Le-Rademacher, Jiaxing Huang, Dan Vogl, Muneer Abidi, Amer Beitinjaneh, Henry Fung, Siddhartha Ganguly, Gerhard Hildebrandt, Leona Holmberg, Matt Kalaycio, Shaji Kumar, Robert Kyle, Hillard Lazarus, Cindy Lee, Richard T. Maziarz, Kenneth Meehan, Joseph Mikhael, Taiga Nishihori, Muthalagu Ramanathan, Saad Usmani, Jason Tay, David Vesole, Baldeep Wirk, Jean Yared, Bipin N. Savani, Cristina Gasparetto, Amrita Krishnan, Tomer Mark, Yago Nieto, Anita D'Souza

Department of Medical Oncology Faculty Papers

Conventional cytogenetics and interphase fluorescence in situ hybridization (FISH) identify high-risk multiple myeloma (HRM) populations characterized by poor outcomes. We analyzed these differences among HRM versus non-HRM populations after upfront autologous hematopoietic cell transplantation (autoHCT). Between 2008 and 2012, 715 patients with multiple myeloma identified by FISH and/or cytogenetic data with upfront autoHCT were identified in the Center for International Blood and Marrow Transplant Research database. HRM was defined as del17p, t(4;14), t(14;16), hypodiploidy (-Y) or chromosome 1 p and 1q abnormalities; all others were non-HRM. Among 125 HRM patients (17.5%), induction with bortezomib and immunomodulatory agents (imids) was higher …

Detection And Characterization Of Circulating Tumor Associated Cells In Metastatic Breast Cancer., Zhaomei Mu, Naoual Benali-Furet, Georges Uzan, Anaëlle Znaty, Zhong Ye, Carmela Paolillo, Chun Wang, Laura Austin, Giovanna Rossi, Paolo Fortina, Hushan Yang, Massimo Cristofanilli

Department of Medical Oncology Faculty Papers

The availability of blood-based diagnostic testing using a non-invasive technique holds promise for real-time monitoring of disease progression and treatment selection. Circulating tumor cells (CTCs) have been used as a prognostic biomarker for the metastatic breast cancer (MBC). The molecular characterization of CTCs is fundamental to the phenotypic identification of malignant cells and description of the relevant genetic alterations that may change according to disease progression and therapy resistance. However, the molecular characterization of CTCs remains a challenge because of the rarity and heterogeneity of CTCs and technological difficulties in the enrichment, isolation and molecular characterization of CTCs. In this …

Tau Phosphorylation At Alzheimer's Disease-Related Ser356 Contributes To Tau Stabilization When Par-1/Mark Activity Is Elevated., Kanae Ando, Mikiko Oka, Yosuke Ohtake, Motoki Hayashishita, Sawako Shimizu, Shin-Ichi Hisanaga, Koichi M. Iijima

Department of Neuroscience Faculty Papers

Abnormal phosphorylation of the microtubule-associated protein tau is observed in many neurodegenerative diseases, including Alzheimer's disease (AD). AD-related phosphorylation of two tau residues, Ser262 and Ser356, by PAR-1/MARK stabilizes tau in the initial phase of mismetabolism, leading to subsequent phosphorylation events, accumulation, and toxicity. However, the relative contribution of phosphorylation at each of these sites to tau stabilization has not yet been elucidated. In a Drosophila model of human tau toxicity, we found that tau was phosphorylated at Ser262, but not at Ser356, and that blocking Ser262 phosphorylation decreased total tau levels. By contrast, when PAR-1 was co-overexpressed with tau, …

Polypharmacy And Potentially Inappropriate Medication Use In Geriatric Oncology., Manvi Sharma, Kah Poh Loh, Ginah Nightingale Pharmd, Bcop, Supriya G. Mohile, Holly M. Holmes

College of Pharmacy Faculty Papers

Polypharmacy is a highly prevalent problem in older persons, and is challenging to assess and improve due to variations in definitions of the problem and the heterogeneous methods of medication review and reduction. The purpose of this review is to summarize evidence regarding the prevalence and impact of polypharmacy in geriatric oncology patients and to provide recommendations for assessment and management. Polypharmacy has somewhat variably been incorporated into geriatric assessment studies in geriatric oncology, and polypharmacy has not been consistently evaluated as a predictor of negative outcomes in patients with cancer. Once screened, interventions for polypharmacy are even more uncertain. …

Recurrent Violent Injury: Magnitude, Risk Factors, And Opportunities For Intervention From A Statewide Analysis., Elinore Kaufman, Kristin L. Rising, Md, Ms, Douglas J. Wiebe, David J. Ebler, Marie L. Crandall, M. Kit Delgado

Department of Emergency Medicine Faculty Papers

INTRODUCTION: Although preventing recurrent violent injury is an important component of a public health approach to interpersonal violence and a common focus of violence intervention programs, the true incidence of recurrent violent injury is unknown. Prior studies have reported recurrence rates from 0.8% to 44%, and risk factors for recurrence are not well established.

METHODS: We used a statewide, all-payer database to perform a retrospective cohort study of emergency department visits for injury due to interpersonal violence in Florida, following up patients injured in 2010 for recurrence through 2012. We assessed risk factors for recurrence with multivariable logistic regression and …

Chemical Modification Of Extracellular Matrix By Cold Atmospheric Plasma-Generated Reactive Species Affects Chondrogenesis And Bone Formation., Peter Eisenhauer, Natalie Chernets, You Song, Danil Dobrynin, Nancy Pleshko, Marla J Steinbeck, Theresa A. Freeman

Department of Orthopaedic Surgery Faculty Papers

The goal of this study was to investigate whether cold plasma generated by dielectric barrier discharge (DBD) modifies extracellular matrices (ECM) to influence chondrogenesis and endochondral ossification. Replacement of cartilage by bone during endochondral ossification is essential in fetal skeletal development, bone growth and fracture healing. Regulation of this process by the ECM occurs through matrix remodelling, involving a variety of cell attachment molecules and growth factors, which influence cell morphology and protein expression. The commercially available ECM, Matrigel, was treated with microsecond or nanosecond pulsed (μsp or nsp, respectively) DBD frequencies conditions at the equivalent frequencies (1 kHz) or …

Mitochondrial Akt Regulation Of Hypoxic Tumor Reprogramming., Young Chan Chae, Valentina Vaira, M. Cecilia Caino, Hsin-Yao Tang, Jae Ho Seo, Andrew V. Kossenkov, Luisa Ottobrini, Cristina Martelli, Giovanni Lucignani, Irene Bertolini, Marco Locatelli, Kelly G. Bryant, Jagadish C. Ghosh, Sofia Lisanti, Bonsu Ku, Silvano Bosari, Lucia R. Languino, David W. Speicher, Dario C. Altieri

Department of Cancer Biology Faculty Papers

Hypoxia is a universal driver of aggressive tumor behavior, but the underlying mechanisms are not completely understood. Using a phosphoproteomics screen, we now show that active Akt accumulates in the mitochondria during hypoxia and phosphorylates pyruvate dehydrogenase kinase 1 (PDK1) on Thr346 to inactivate the pyruvate dehydrogenase complex. In turn, this pathway switches tumor metabolism toward glycolysis, antagonizes apoptosis and autophagy, dampens oxidative stress, and maintains tumor cell proliferation in the face of severe hypoxia. Mitochondrial Akt-PDK1 signaling correlates with unfavorable prognostic markers and shorter survival in glioma patients and may provide an "actionable" therapeutic target in cancer.

Statins And Exercise Training Response In Heart Failure Patients: Insights From Hf-Action., Jacob P. Kelly, Allison Dunning, Phillip J. Schulte, Mona Fiuzat, Eric S. Leifer, Jerome L. Fleg, Lawton S. Cooper, Steven J. Keteyian, Dalane W. Kitzman, Ileana L. Pina, William E. Kraus, David J. Whellan, Christopher M. O'Connor, Robert J. Mentz

Division of Cardiology Faculty Papers

OBJECTIVES: The aim of this study was to assess for a treatment interaction between statin use and exercise training (ET) response.

BACKGROUND: Recent data suggest that statins may attenuate ET response, but limited data exist in patients with heart failure (HF).

METHODS: HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) was a randomized trial of 2,331 patients with chronic HF with ejection fraction ≤35% who were randomized to usual care with or without ET. We evaluated whether there was a treatment interaction between statins and ET response for the change in quality of life and aerobic capacity …

Adverse Drug Effects And Preoperative Medication Factors Related To Perioperative Low-Dose Ketamine Infusions., Eric S. Schwenk, Stephen F. Goldberg, Ronak D. Patel, Jon Zhou, Douglas R. Adams, Jaime L. Baratta, Eugene R. Viscusi, Richard H. Epstein

Department of Anesthesiology Faculty Papers

High-dose opioid administration is associated with significant adverse events. Evidence suggests that low-dose ketamine infusions improve perioperative analgesia over conventional opioid management, but usage is highly variable. Ketamine's adverse drug effects (ADEs) are well known, but their prevalence during low-dose infusions in a clinical setting and how often they lead to infusion discontinuation are unknown. The purposes of this study were 3-fold: (1) to identify patient factors associated with initiation of ketamine infusions during spine surgery, (2) to identify specific spine procedures in which ketamine has been used most frequently, and (3) to identify ADEs associated with postoperative ketamine infusions …

Adiponectin Ameliorates The Apoptotic Effects Of Paraquat On Alveolar Type Ⅱ Cells Via Improvements In Mitochondrial Function., Yarong He, Liqun Zou, Yaxiong Zhou, Hai Hu, Rong Yao, Yaowen Jiang, Wayne Bond Lau, Tun Yuan, Wen Huang, Zhi Zeng, Yu Cao

Department of Emergency Medicine Faculty Papers

Previous studies have demonstrated that excessive reactive oxygen/nitrogen species (ROS/RNS)‑induced apoptosis is an important feature of the injury to the lung epithelium in paraquat (PQ) poisoning. However the precise mechanisms of PQ‑induced dysfunction of the mitochondria, where ROS/RNS are predominantly produced, remain to be fully elucidated. Whether globular adiponectin (gAd), a potent molecule protective to mitochondria, regulates the mitochondrial function of alveolar type II cells to reduce PQ‑induced ROS/RNS production remains to be investigated. The current study aimed to investigate the precise mechanisms of PQ poisoning in the mitochondria of alveolar type II cells, and to elucidate the role of …

Franklin Delano Roosevelt: The Diagnosis Of Poliomyelitis Revisited., John F. Ditunno, Jr, Bruce E. Becker, Gerald J. Herbison

Department of Rehabilitation Medicine Faculty Papers

Revisiting the ailments of famous historical persons in light of contemporary medical understanding has become a common academic hobby. Public discussion of Franklin Delano Roosevelt's (FDR) diagnosis of poliomyelitis after his sudden onset of paralysis in 1921 has received just such a revisitation. Recently, this 2003 historical analysis has been referenced widely on the Internet and in biographies, raising speculation that his actual diagnosis should have been Guillain-Barré Syndrome, a noncontagious disease of the peripheral nervous system rather than poliomyelitis. The authors of that 2003 analysis used a statistical analysis of his case by selectively choosing some of his reported …

Heart Rhythm Monitoring Strategies For Cryptogenic Stroke: 2015 Diagnostics And Monitoring Stroke Focus Group Report., Gregory W. Albers, Richard A. Bernstein, Johannes Brachmann, John Camm, J. Donald Easton, Peter Fromm, Shinya Goto, Christopher B. Granger, Stefan H. Hohnloser, Elaine Hylek, Amir K. Jaffer, Derk W. Krieger, Rod Passman, Jesse M. Pines, Shelby D. Reed, Peter M. Rothwell, Peter R. Kowey

Department of Medicine Faculty Papers

No abstract provided.

Big Data Transforms Discovery-Utilization Therapeutics Continuum., Scott A. Waldman, Andre Terzic

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Enabling omic technologies adopt a holistic view to produce unprecedented insights into the molecular underpinnings of health and disease, in part, by generating massive high-dimensional biological data. Leveraging these systems-level insights as an engine driving the healthcare evolution is maximized through integration with medical, demographic, and environmental datasets from individuals to populations. Big data analytics has accordingly emerged to add value to the technical aspects of storage, transfer, and analysis required for merging vast arrays of omic-, clinical-, and eco-datasets. In turn, this new field at the interface of biology, medicine, and information science is systematically transforming modern therapeutics across …

Obesity-Induced Colorectal Cancer Is Driven By Caloric Silencing Of The Guanylin-Gucy2c Paracrine Signaling Axis., Jieru E. Lin, Francheska Colon-Gonzalez, Erik S. Blomain, Gilbert W. Kim, Amanda Aing, Brian Stoecker, Justin Rock, Adam E. Snook, Tingting Zhan, Terry M. Hyslop, Michal Tomczak, Richard S. Blumberg, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Obesity is a well-known risk factor for colorectal cancer but precisely how it influences risks of malignancy remains unclear. During colon cancer development in humans or animals, attenuation of the colonic cell surface receptor guanylyl cyclase C (GUCY2C) that occurs due to loss of its paracrine hormone ligand guanylin contributes universally to malignant progression. In this study, we explored a link between obesity and GUCY2C silencing in colorectal cancer. Using genetically engineered mice on different diets, we found that diet-induced obesity caused a loss of guanylin expression in the colon with subsequent GUCY2C silencing, epithelial dysfunction, and tumorigenesis. Mechanistic investigations …

Cogstate Computerized Memory Tests In Patients With Brain Metastases: Secondary Endpoint Results Of Nrg Oncology Rtog 0933., Chip Caine, Snehal Deshmukh, Vinai Gondi, Minesh Mehta, Wolfgang Tomé, Benjamin W. Corn, Andrew Kanner, Howard Rowley, Vijayananda Kundapur, Albert Denittis, Jeffrey Noah Greenspoon, Andre A. Konski, Glenn S. Bauman, Adam Raben, Wenyin Shi, Merideth Wendland, Lisa Kachnic

Department of Radiation Oncology Faculty Papers

Whole brain radiotherapy (WBRT) is associated with memory dysfunction. As part of NRG Oncology RTOG 0933, a phase II study of WBRT for brain metastases that conformally avoided the hippocampal stem cell compartment (HA-WBRT), memory was assessed pre- and post-HA-WBRT using both traditional and computerized memory tests. We examined whether the computerized tests yielded similar findings and might serve as possible alternatives for assessment of memory in multi-institution clinical trials. Adult patients with brain metastases received HA-WBRT to 30 Gy in ten fractions and completed Hopkins Verbal Learning Test-Revised (HVLT-R), CogState International Shopping List Test (ISLT) and One Card Learning …

Endothelial Cells Expressing Endothelial And Mesenchymal Cell Gene Products In Lung Tissue From Patients With Systemic Sclerosis-Associated Interstitial Lung Disease., Fabian A. Mendoza, Sonsoles Piera-Velazquez, John L. Farber, Carol Feghali-Bostwick, Sergio A. Jimenez

Department of Dermatology and Cutaneous Biology Faculty Papers

OBJECTIVE: To examine whether lung endothelial cells (ECs) from patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD) express mesenchymal cell-specific proteins and gene transcripts, indicative of the occurrence of endothelial-to-mesenchymal phenotypic transition (EndoMT).

METHODS: Lung tissue from 6 patients with SSc-associated pulmonary fibrosis was examined by histopathology and immunohistochemistry. Confocal laser microscopy was utilized to assess the simultaneous expression of EC and myofibroblast molecular markers. CD31+CD102+ ECs were isolated from the lung tissue of 2 patients with SSc-associated ILD and 2 normal control subjects, and the expression of EC and mesenchymal cell markers and other relevant genes was analyzed …

Bioinnovation Enterprise: An Engine Driving Breakthrough Therapies., Scott A. Waldman, Andre Terzic

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Biological advances have radically expanded our insights into the underpinnings of health and disease. New knowledge has formed the substrate for translation-expedited in turn by the biotechnology and pharmaceutical industry into novel therapeutic solutions impacting the management of patients and populations. Indeed, this Bioinnovation Enterprise has become the dominant growth sector in drug development and the engine driving the translation of breakthrough therapies worldwide. This annual Therapeutic Innovations issue highlights recent exceptional advances by the Bioinnovation Enterprise in translating molecular insights in pathobiology into transformative therapies.