Medical Specialties Commons^™

Completion Dissection Or Observation For Sentinel-Node Metastasis In Melanoma., Mark Faries, John F Thompson, Alistair J Cochran, Robert H Andtbacka, Nicola Mozzillo, Jonathan S Zager, Tiina Jahkola, Tawnya L Bowles, Alessandro Testori, Peter D Beitsch, Harald J Hoekstra, Marc Moncrieff, Christian Ingvar, Michel W J M Wouters, Michael S Sabel, Edward A Levine, Doreen Agnese, Michael Henderson, Reinhard Dummer, Carlo R Rossi, Rogerio I Neves, Steven D Trocha, Frances Wright, David R Byrd, Maurice Matter, Eddy Hsueh, Alastair Mackenzie-Ross, Douglas B Johnson, Patrick Terheyden, Adam C Berger, Tara L Huston, Jeffrey D Wayne, B Mark Smithers, Heather B Neuman, Schlomo Schneebaum, Jeffrey E Gershenwald, Charlotte E Ariyan, Darius C Desai, Lisa Jacobs, Kelly M Mcmasters, Anja Gesierich, Peter Hersey, Steven D Bines, John M Kane, Richard J Barth, Gregory Mckinnon, Jeffrey M Farma, Erwin Schultz, Sergi Vidal-Sicart, Richard A Hoefer, James M Lewis, Randall Scheri, Mark C Kelley, Omgo E Nieweg, R Dirk Noyes, Dave S B Hoon, He-Jing Wang, David A Elashoff, Robert M Elashoff

Articles, Abstracts, and Reports

BACKGROUND: Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear.

METHODS: In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis.

RESULTS: Immediate completion …

Pineal Gland Agenesis: Review And Case Illustration., Marcus A Cox, Michele Davis, Vlad Voin, Mohammadali Shoja, Rod J Oskouian, Marios Loukas, R Shane Tubbs

Articles, Abstracts, and Reports

Agenesis of the pineal gland has rarely been reported in the medical literature. Herein, we report a cadaveric specimen found to have agenesis of the pineal gland. The remaining gross examination of the brain was normal. A review of the literature was performed on this unusual finding.

Genome-Wide Chromatin Accessibility, Dna Methylation And Gene Expression Analysis Of Histone Deacetylase Inhibition In Triple-Negative Breast Cancer., Matias A Bustos, Matthew P Salomon, Nellie Nelson, Sandy C Hsu, Maggie L Dinome, Dave S B Hoon, Diego M Marzese

Articles, Abstracts, and Reports

Triple-negative breast cancer (TNBC), especially the subset with a basal phenotype, represents the most aggressive subtype of breast cancer. Unlike other solid tumors, TNBCs harbor a low number of driver mutations. Conversely, we and others have demonstrated a significant impact of epigenetic alterations, including DNA methylation and histone post-translational modifications, affecting TNBCs. Due to the promising results in pre-clinical studies, histone deacetylase inhibitors (HDACi) are currently being tested in several clinical trials for breast cancer and other solid tumors. However, the genome-wide epigenetic and transcriptomic implications of HDAC inhibition are still poorly understood. Here, we provide detailed information about the …

Modulation Of Bax And Mtor For Cancer Therapeutics., Rui Li, Chunyong Ding, Jun Zhang, Maohua Xie, Dongkyoo Park, Ye Ding, Guo Chen, Guojing Zhang, Melissa Gilbert-Ross, Wei Zhou, Adam I Marcus, Shi-Yong Sun, Zhuo G Chen, Gabriel L Sica, Suresh S Ramalingam, Andrew T Magis, Haian Fu, Fadlo R Khuri, Walter J Curran, Taofeek K Owonikoko, Dong M Shin, Jia Zhou, Xingming Deng

Articles, Abstracts, and Reports

A rationale exists for pharmacologic manipulation of the serine (S)184 phosphorylation site of the proapoptotic Bcl2 family member Bax as an anticancer strategy. Here, we report the refinement of the Bax agonist SMBA1 to generate CYD-2-11, which has characteristics of a suitable clinical lead compound. CYD-2-11 targeted the structural pocket proximal to S184 in the C-terminal region of Bax, directly activating its proapoptotic activity by inducing a conformational change enabling formation of Bax homooligomers in mitochondrial membranes. In murine models of small-cell and non-small cell lung cancers, including patient-derived xenograft and the genetically engineered mutant KRAS-driven lung cancer models, CYD-2-11 …

The Quest For Sustained Multiple Morbidity Reduction In Very Low-Birth-Weight Infants: The Antifragility Project., Joseph Kaempf, N M Schmidt, S Rogers, C Novack, M Friant, L Wang, N Tipping

Articles, Abstracts, and Reports

OBJECTIVE: Can a comprehensive, explicitly directive evidence-based guideline for all therapies that might affect the major morbidities of very low-birth-weight (VLBW) infants help a neonatal intensive care unit (NICU) further improve generally favorable morbidity rates? Can Antifragility principles of provider adaptive growth from stressors, enhanced infant risk assessment and adherence to effective therapies minimize unproven treatments and reduce all morbidities?

STUDY DESIGN: Prospectively planned observational trial in VLBW infants: control group born October 2011 to September 2013 and study group October 2013 to September 2015. Multi-disciplinary evidence-based review assigned all NICU treatments into one of four distinct categories: (1) always …

The First Histological Analysis Of The Tissues Lining The Fossa Navicularis: Insights To Its Etiology., Sarvenaz Sheikh, Joe Iwanaga, Steven Rostad, Tarush Rustagi, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

The fossa navicularis (FN) is an anatomical variant on the ventral surface of the basilar part of the occipital bone that, to date, has only been investigated in bone specimens. We aim to clarify the structure of the fossa navicularis by gross anatomical, radiological, and histological methods. The FN was found in the occipital bone of the Caucasian male cadaver. There was no bony or histological continuity between the FN and posterior cranial fossa. The histological analysis found that the overlying tissue was composed of loose connective tissue with a mixture of collagen and elastic fibers and a vascular matrix …

Internal Hernia Of The Greater Omentum: Cadaveric Findings Of A Previously Unreported Variant., Andrea Andrea, Vy Tran, Cameron K Schmidt, Christian Fisahn, Joe Iwanaga, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

Transomental hernias (TOHs) are a rare finding, constituting a fraction of all intestinal hernias. Here, we report the cadaveric discovery of a spontaneous TOH involving the sigmoid colon in an 82-year-old female and discuss the relevant literature. To our knowledge, a TOH involving the sigmoid colon has not been previously reported.

Johann Gaspar Spurzheim: A Life Dedicated To Phrenology., Mohammad Bilal, Bryan Edwards, Marios Loukas, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

Loved for his empathetic nature but admired for his analytical mind, Gaspar Spurzheim (1776-1832) was a prominent contributor to phrenology, a field of neuroscience focused on studying the shapes of the skulls in relation to the activity levels of certain functional areas of the brain. This curiosity about the connection between physical characteristics and brain function was seeded in the young mind of Spurzheim when he observed that classmates with seemingly superb memories also appeared to have bright eyes. It launched Spurzheim on a journey to study the shape and function of the brain, which eventually led him to his …

Median Nerve Palsies Due To Injections: A Review., Andrea Andrea, Jocelyn R Gonzales, Joe Iwanaga, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

Injection nerve palsy (INP) in the median nerve is an iatrogenic peripheral nerve injury that can be inflicted by a faulty intramuscular injection in the median nerve area. The literature reports a 2% incidence of INP among all peripheral nerve injuries. The incidence of INP in developed countries has decreased significantly during the past decade, but the injury appears to remain prevalent in developing countries. A deep understanding of the anatomy of the peripheral nerves, and a precise intramuscular injection technique, have been shown to be vital for preventing INP in the median nerve. Debates continue regarding what, if any, …

A Cell-Surface Membrane Protein Signature For Glioblastoma., Dhimankrishna Ghosh, Cory C Funk, Juan Caballero, Nameeta Shah, Katherine Rouleau, John C Earls, Liliana Soroceanu, Greg Foltz, Charles Cobbs, Nathan D Price, Leroy Hood

Articles, Abstracts, and Reports

We present a systems strategy that facilitated the development of a molecular signature for glioblastoma (GBM), composed of 33 cell-surface transmembrane proteins. This molecular signature, GBMSig, was developed through the integration of cell-surface proteomics and transcriptomics from patient tumors in the REMBRANDT (n = 228) and TCGA datasets (n = 547) and can separate GBM patients from control individuals with a Matthew's correlation coefficient value of 0.87 in a lock-down test. Functionally, 17/33 GBMSig proteins are associated with transforming growth factor β signaling pathways, including CD47, SLC16A1, HMOX1, and MRC2. Knockdown of these genes impaired GBM invasion, reflecting their role …

Impact Of Ibrutinib Dose Adherence On Therapeutic Efficacy In Patients With Previously Treated Cll/Sll., Paul M Barr, Jennifer R Brown, Peter Hillmen, Susan O'Brien, Jacqueline C Barrientos, Nishitha M Reddy, Steven Coutre, Stephen P Mulligan, Ulrich Jaeger, Richard R Furman, Florence Cymbalista, Marco Montillo, Claire Dearden, Tadeusz Robak, Carol Moreno, John M Pagel, Jan A Burger, Samuel Suzuki, Juthamas Sukbuntherng, George Cole, Danelle F James, John C Byrd

Articles, Abstracts, and Reports

Ibrutinib, an oral inhibitor of Bruton's tyrosine kinase (BTK), at a once-daily dose of 420 mg achieved BTK active-site occupancy in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) that was maintained at 24 hours. It is unknown if intermittent interruption of ibrutinib therapy contributes to altered clinical outcomes. We therefore evaluated the effect of ibrutinib dose adherence on patient outcomes in the phase 3 RESONATE trial. The overall mean dose intensity (DI) was 95% with median treatment duration of ∼9 months. Pharmacokinetic assessment of ibrutinib exposure at 420-mg dose suggested similar exposure regardless of patient weight or age. …

Ccr4 Is A Determinant Of Melanoma Brain Metastasis., Anat Klein, Orit Sagi-Assif, Tsipi Meshel, Alona Telerman, Sivan Izraely, Shlomit Ben-Menachem, Jagadeesh Bayry, Diego M Marzese, Shuichi Ohe, Dave S B Hoon, Neta Erez, Isaac P Witz

Articles, Abstracts, and Reports

We previously identified the chemokine receptor CCR4 as part of the molecular signature of melanoma brain metastasis. The aim of this study was to determine the functional significance of CCR4 in melanoma brain metastasis. We show that CCR4 is more highly expressed by brain metastasizing melanoma cells than by local cutaneous cells from the same melanoma. Moreover, we found that the expression of CCR4 is significantly higher in paired clinical specimens of melanoma metastases than in samples of primary tumors from the same patients. Notably, the expression of the CCR4 ligands, Ccl22 and Ccl17 is upregulated at the earliest stages …

Biomarkers Of Acute Stroke Etiology (Base) Study Methodology., Edward C Jauch, Andrew D Barreto, Joseph P Broderick, Doug M Char, Brett L Cucchiara, Thomas G Devlin, Alison J Haddock, William J Hicks, Brian C Hiestand, Glen C Jickling, Jeff June, David S Liebeskind, Ted J Lowenkopf, Joseph B Miller, John O'Neill, Tim L Schoonover, Frank R Sharp, W Frank Peacock

Articles, Abstracts, and Reports

Acute ischemic stroke affects over 800,000 US adults annually, with hundreds of thousands more experiencing a transient ischemic attack. Emergent evaluation, prompt acute treatment, and identification of stroke or TIA (transient ischemic attack) etiology for specific secondary prevention are critical for decreasing further morbidity and mortality of cerebrovascular disease. The Biomarkers of Acute Stroke Etiology (BASE) study is a multicenter observational study to identify serum markers defining the etiology of acute ischemic stroke. Observational trial of patients presenting to the hospital within 24 h of stroke onset. Blood samples are collected at arrival, 24, and 48 h later, and RNA …

Undetected Small Accessory Mental Foramina Using Cone-Beam Computed Tomography., Joe Iwanaga, Koichi Watanabe, Tsuyoshi Saga, Shogo Kikuta, Yoko Tabira, Sadaharu Kitashima, Christian Fisahn, Fernando Alonso, R Shane Tubbs, Jingo Kusukawa, Koh-Ichi Yamaki

Articles, Abstracts, and Reports

INTRODUCTION: The accessory foramina could not be identified on some imaging modalities such as surface-rendered images. The purpose of this study was to investigate the ability of surface-rendered images in detecting these foramina.

MATERIALS AND METHODS: We analyzed 20 accessory mental foramina (AMF) in nine mandibles removed from cadavers with cone-beam computed tomography (CBCT) and assessed in surface-rendered images. All AMF were divided into three groups depending on their visibility.

RESULTS: Group 1 included AMF that were clearly visible as foramina, Group 2 were not clearly visible but could be recognized with concave parts, and Group 3 were not visible …

A Novel Agonist Of The Trif Pathway Induces A Cellular State Refractory To Replication Of Zika, Chikungunya, And Dengue Viruses., Kara M Pryke, Jinu Abraham, Tina M Sali, Bryan J Gall, Iris Archer, Andrew Liu, Shelly Bambina, Jason R Baird, Michael J. Gough, Marita Chakhtoura, Elias K Haddad, Ilsa T Kirby, Aaron Nilsen, Daniel N Streblow, Alec J Hirsch, Jessica L Smith, Victor R Defilippis

Articles, Abstracts, and Reports

The ongoing concurrent outbreaks of Zika, Chikungunya, and dengue viruses in Latin America and the Caribbean highlight the need for development of broad-spectrum antiviral treatments. The type I interferon (IFN) system has evolved in vertebrates to generate tissue responses that actively block replication of multiple known and potentially zoonotic viruses. As such, its control and activation through pharmacological agents may represent a novel therapeutic strategy for simultaneously impairing growth of multiple virus types and rendering host populations resistant to virus spread. In light of this strategy's potential, we undertook a screen to identify novel interferon-activating small molecules. Here, we describe …

Sex-Specific Associations Of Maternal Birthweight With Offspring Birthweight In The Omega Study., Collette N Ncube, Amelia R Gavin, Michelle A Williams, Chunfang Qiu, Tanya K Sorensen, Daniel A Enquobahrie

Articles, Abstracts, and Reports

PURPOSE: We investigated nonlinear and offspring sex-specific associations of maternal birthweight (BW) with offspring BW among participants of the Omega study, a pregnancy cohort.

METHODS: Maternal BW was modeled as a continuous variable, linear spline and binary variable indicating low birthweight (LBW;≥2500 grams). Offspring BW was modeled as a continuous and binary variable in regression models. Nonlinearity was assessed using likelihood ratio tests (LRTs) in marginal linear spline models.

RESULTS: For every 100-gram increase of maternal BW, offspring BW increased by 22.29 (95% CI: 17.57, 27.02) or 23.41 (95% CI: 6.87, 39.96) grams among mothers with normal BW or born …

The Acttion-Aps-Aapm Pain Taxonomy (Aaapt) Multidimensional Approach To Classifying Acute Pain Conditions., Michael L Kent, Patrick J Tighe, Inna Belfer, Timothy J Brennan, Stephen Bruehl, Chad M Brummett, Chester C Buckenmaier, Asokumar Buvanendran, Robert I Cohen, Paul Desjardins, David Edwards, Roger Fillingim, Jennifer Gewandter, Debra B Gordon, Robert W Hurley, Henrik Kehlet, John D Loeser, Sean Mackey, Samuel A Mclean, Rosemary Polomano, Siamak Rahman, Srinivasa Raja, Michael Rowbotham, Santhanam Suresh, Bernard Schachtel, Kristin Schreiber, Mark Schumacher, Brett Stacey, Steven P Stanos, Knox Todd, Dennis C Turk, Steven J Weisman, Christopher Wu, Daniel B Carr, Robert H Dworkin, Gregory Terman

Articles, Abstracts, and Reports

Objective: With the increasing societal awareness of the prevalence and impact of acute pain, there is a need to develop an acute pain classification system that both reflects contemporary mechanistic insights and helps guide future research and treatment. Existing classifications of acute pain conditions are limiting, with a predominant focus on the sensory experience (e.g., pain intensity) and pharmacologic consumption. Consequently, there is a need to more broadly characterize and classify the multidimensional experience of acute pain.

Setting: Consensus report following expert panel involving the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), American Pain Society …

Defining Outcome Measures For Psoriatic Arthritis: A Report From The Grappa-Omeract Working Group., Alexis Ogdie, Maarten De Wit, Kristina Callis Duffin, Willemina Campbell, Jeffrey Chau, Laura C Coates, Lihi Eder, Musaab Elmamoun, Oliver Fitzgerald, Dafna D Gladman, Niti Goel, Jana James, Umut Kalyoncu, John Latella, Chris Lindsay, Philip Mease, Denis O'Sullivan, Ingrid Steinkoenig, Vibeke Strand, William Tillett, Ana-Maria Orbai

Articles, Abstracts, and Reports

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis (PsA) Core Set working group recently published the updated 2016 psoriatic arthritis (PsA) core domain set, a set of disease features that should be measured in all clinical trials. At the GRAPPA annual meeting in July 2016, the PsA working group presented the updated PsA core domain set endorsed by 90% of participants at OMERACT in May 2016 and drafted a roadmap for the development of the PsA core outcome measurement set. In this manuscript, we review the development process of the …

Restriction Spectrum Imaging Improves Risk Stratification In Patients With Glioblastoma., A P Krishnan, R Karunamuni, K M Leyden, T M Seibert, R L Delfanti, J M Kuperman, H Bartsch, P Elbe, A Srikant, A M Dale, Santosh Kesari, D E Piccioni, J A Hattangadi-Gluth, N Farid, C R Mcdonald, N S White

Articles, Abstracts, and Reports

BACKGROUND AND PURPOSE: ADC as a marker of tumor cellularity has been promising for evaluating the response to therapy in patients with glioblastoma but does not successfully stratify patients according to outcomes, especially in the upfront setting. Here we investigate whether restriction spectrum imaging, an advanced diffusion imaging model, performed after an operation but before radiation therapy, could improve risk stratification in patients with newly diagnosed glioblastoma relative to ADC.

MATERIALS AND METHODS: Pre-radiation therapy diffusion-weighted and structural imaging of 40 patients with glioblastoma were examined retrospectively. Restriction spectrum imaging and ADC-based hypercellularity volume fraction (restriction spectrum imaging-FLAIR volume fraction, …

A Phase Ib/Ii Study Of Cabozantinib (Xl184) With Or Without Erlotinib In Patients With Non-Small Cell Lung Cancer., Heather A Wakelee, Scott Gettinger, Jeffrey Engelman, Pasi A Jänne, Howard J. West, Deepa S Subramaniam, Joseph Leach, Michael Wax, Yifah Yaron, Dale R Miles, Primo N Lara

Articles, Abstracts, and Reports

PURPOSE: Cabozantinib is a multi-kinase inhibitor that targets MET, AXL, and VEGFR2, and may synergize with EGFR inhibition in NSCLC. Cabozantinib was assessed alone or in combination with erlotinib in patients with progressive NSCLC and EGFR mutations who had previously received erlotinib.

METHODS: This was a phase Ib/II study (NCT00596648). The primary objectives of phase I were to assess the safety, pharmacokinetics, and pharmacodynamics and to determine maximum tolerated dose (MTD) of cabozantinib plus erlotinib in patients who failed prior erlotinib treatment. In phase II, patients with prior response or stable disease with erlotinib who progressed were randomized to single-agent …

Induction And Characterization Of Anti-Tumor Endothelium Immunity Elicited By Vallovax Therapeutic Cancer Vaccine., Samuel C Wagner, Thomas E Ichim, Vladimir Bogin, Wei-Ping Min, Francisco Silva, Amit N Patel, Santosh Kesari

Articles, Abstracts, and Reports

ValloVax is a placental endothelium derived vaccine which induces tissue-nonspecific antitumor immunity by blocking tumor angiogesis. To elucidate mechanisms of action, we showed that production of ValloVax, which involves treating placental endothelial cells with IFN-gamma, results in upregulation of HLA and costimulatory molecules. It was shown that in mixed lymphocyte reaction, ValloVax induces Type I cytokines and allo-proliferative responses. Plasma from ValloVax immunized mice was capable of killing in vitro tumor-like endothelium but not control endothelium. Using defined antigens associated with tumor endothelial cells, specific molecular entities were identified as being targeted by ValloVax induced antibodies. Binding of predominantly IgG …

Longitudinal Peripheral Blood Transcriptional Analysis Of A Patient With Severe Ebola Virus Disease., John C Kash, Kathie-Anne Walters, Jason Kindrachuk, David Baxter, Kelsey Scherler, Krisztina B Janosko, Rick D Adams, Andrew S Herbert, Rebekah M James, Spencer W Stonier, Matthew J Memoli, John M Dye, Richard T Davey, Daniel S Chertow, Jeffery K Taubenberger

Articles, Abstracts, and Reports

The 2013-2015 outbreak of Ebola virus disease in Guinea, Liberia, and Sierra Leone was unprecedented in the number of documented cases, but there have been few published reports on immune responses in clinical cases and their relationships with the course of illness and severity of Ebola virus disease. Symptoms of Ebola virus disease can include severe headache, myalgia, asthenia, fever, fatigue, diarrhea, vomiting, abdominal pain, and hemorrhage. Although experimental treatments are in development, there are no current U.S. Food and Drug Administration-approved vaccines or therapies. We report a detailed study of host gene expression as measured by microarray in daily …

Multiple Large Perineural (Tarlov) Cysts In The Sacrum Of A Cadaver: A Case Report And Review., Jocelyn Gonzales, Joe Iwanaga, Nitsa Topale, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

Tarlov or perineural cysts are cerebrospinal fluid (CSF)-filled sacs found between the perineurium and epineurium of the nerve roots. It is still unsure whether the origin of these cysts is intradural or extradural. They can either be asymptomatic or create a variety of negative impacts on comfort and quality of life. In this case report, we describe the presentation of multiple Tarlov cysts including one large cyst discovered during a routine cadaveric spinal dissection and the relevant and related literature. To our knowledge, this is the only cadaveric case report of Tarlov cysts and offers an interesting window into their …

Update On The Notochord Including Its Embryology, Molecular Development, And Pathology: A Primer For The Clinician., Tushar Ramesh, Sai V Nagula, Gabrielle G Tardieu, Erfanul Saker, Mohammadali Shoja, Marios Loukas, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

The notochord is a rod-like embryological structure, which plays a vital role in the development of the vertebrate. Though embryological, remnants of this structure have been observed in the nucleus pulposus of the intervertebral discs of normal adults. Pathologically, these remnants can give rise to slow-growing and recurrent notochord-derived tumors called chordomas. Using standard search engines, the literature was reviewed regarding the anatomy, embryology, molecular development, and pathology of the human notochord. Clinicians who interpret imaging or treat patients with pathologies linked to the notochord should have a good working knowledge of its development and pathology.

The Northwest Participant And Clinical Interactions Network: Increasing Opportunities For Patients To Participate In Research Across The Northwestern United States., Laura-Mae Baldwin, Laurie Hassell, Cindi Laukes, Michelle Doyle, Anne Reedy, Brenda Mollis, Sandra Albritton, Elizabeth Ciemins, Robert Coker, Jeannine Brant, Katherine Tuttle, Laura Baker, Bonnie Ramsey

Articles, Abstracts, and Reports

INTRODUCTION: The Institute of Translational Health Sciences (ITHS) promotes and supports translational research collaboration between clinicians, communities, and investigators across the five-state Washington, Wyoming, Alaska, Montana, and Idaho (WWAMI) region. The ITHS has developed a collaborative regional clinical research network, the Northwest Participant & Clinical Interactions Network (NW PCI), involving 12 diverse clinical health systems and academic institutions.

METHODS: This descriptive article details NW PCI's development, infrastructure and governance, tools, characteristics, and initial outcomes.

RESULTS: Regional NW PCI sites are conducting largely industry-sponsored studies; they are interested in including more grant-funded research. Regional NW PCI sites had over 1,240 open …

Long-Term Outcomes After Autologous Hematopoietic Stem Cell Transplantation For Multiple Sclerosis., Paolo A Muraro, Marcelo Pasquini, Harold L Atkins, James D Bowen, Dominique Farge, Athanasios Fassas, Mark S Freedman, George E Georges, Francesca Gualandi, Nelson Hamerschlak, Eva Havrdova, Vassilios K Kimiskidis, Tomas Kozak, Giovanni L Mancardi, Luca Massacesi, Daniela A Moraes, Richard A Nash, Steven Pavletic, Jian Ouyang, Montserrat Rovira, Albert Saiz, Belinda Simoes, Marek Trnený, Lin Zhu, Manuela Badoglio, Xiaobo Zhong, Maria Pia Sormani, Riccardo Saccardi

Articles, Abstracts, and Reports

Importance: Autologous hematopoietic stem cell transplantation (AHSCT) may be effective in aggressive forms of multiple sclerosis (MS) that fail to respond to standard therapies.

Objective: To evaluate the long-term outcomes in patients who underwent AHSCT for the treatment of MS in a large multicenter cohort.

Design, Setting, and Participants: Data were obtained in a multicenter, observational, retrospective cohort study. Eligibility criteria were receipt of AHSCT for the treatment of MS between January 1995 and December 2006 and the availability of a prespecified minimum data set comprising the disease subtype at baseline; the Expanded Disability Status Scale (EDSS) score at baseline; …

Curcumin And Turmeric Modulate The Tumor-Promoting Effects Of Iron In Vitro., Donald J Messner, Todd Robinson, Kris V Kowdley

Articles, Abstracts, and Reports

Free or loosely chelated iron has tumor-promoting properties in vitro. Curcumin, a polyphenol derived from the food spice turmeric (Curcuma longa), is a potent antioxidant that binds iron. The primary aim of this study was to investigate whether curcuminoids prevent tumor-promoting effects of iron in T51B cells, a non-neoplastic rat liver epithelial cell line. Purified curcuminoids (curcumin) or a standardized turmeric extract similarly reduced oxidative stress and cytotoxicity associated with iron overload (IC

Evaluation Of Evidence Of Adrenal Insufficiency In Trials Of Normocortisolemic Patients Treated With Mifepristone., Kevin C J Yuen, Andreas Moraitis, Dat Nguyen

Articles, Abstracts, and Reports

Context: Adrenal insufficiency (AI) is an important medical concern for clinicians when normocortisolemia is achieved during treatment of endogenous Cushing syndrome (CS).

Objective: To examine symptoms of potential AI in a large population of normocortisolemic patients without CS treated with mifepristone, a glucocorticoid receptor antagonist indicated for the treatment of patients with CS.

Methods: We conducted a pooled safety analysis of five phase 3, placebo-controlled clinical trials of normocortisolemic adults without CS but diagnosed with psychotic depression (n = 1460). Patients were treated with once-daily mifepristone 300 mg (n = 110), 600 mg (n = 471), or 1200 mg (n …

Research Conference Summary From The 2014 International Task Force On, Hendrik Rosewich, Matthew T Sweney, Suzanne Debrosse, Kevin Ess, Laurie Ozelius, Eva Andermann, Frederick Andermann, Gene Andrasco, Alice Belgrade, Allison Brashear, Sharon Ciccodicola, Lynn Egan, Alfred L George, Aga Lewelt, Joshua Magelby, Mario Merida, Tara Newcomb, Vicky Platt, Dominic Poncelin, Sandra Reyna, Masayuki Sasaki, Márcio A Sotero De Menezes, Kathleen Sweadner, Louis Viollet, Mary Zupanc, Kenneth Silver, Kathryn Swoboda

Articles, Abstracts, and Reports

OBJECTIVE:

METHODS: In 2014, the Alternating Hemiplegia of Childhood Foundation hosted a multidisciplinary workshop intended to address fundamental challenges surrounding the diagnosis and management of individuals with

RESULTS: Workshop attendees were charged with the following: (1) to achieve consensus on expanded diagnostic criteria to facilitate the identification of additional patients, intended to supplement existing syndrome-specific diagnostic paradigms; (2) to standardize definitions for the broad range of paroxysmal manifestations associated with AHC to disseminate to families; (3) to create clinical recommendations for common recurrent issues facing families and medical care providers; (4) to review data related to the death of individuals …

Perioperative Vision Loss In Cervical Spinal Surgery., Brandon C Gabel, Arthur Lam, Jens R Chapman, Rod J Oskouian, Ahmad Nassr, Bradford L Currier, Arjun S Sebastian, Paul M Arnold, Steven Hamilton, Michael G Fehlings, Thomas E Mroz, K Daniel Riew

Articles, Abstracts, and Reports

STUDY DESIGN: Retrospective multicenter case series.

OBJECTIVE: To assess the rate of perioperative vision loss following cervical spinal surgery.

METHODS: Medical records for 17 625 patients from 21 high-volume surgical centers from the AOSpine North America Clinical Research Network who received cervical spine surgery (levels from C2 to C7) between January 1, 2005, and December 31, 2011, inclusive, were reviewed to identify occurrences of vision loss following surgery.

RESULTS: Of the 17 625 patients in the registry, there were 13 946 patients assessed for the complication of blindness. There were 9591 cases that involved only anterior surgical approaches; the remaining …