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Articles 1321 - 1350 of 1488

Full-Text Articles in Medical Specialties

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 Oct 2017

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 …


Updating The Psoriatic Arthritis (Psa) Core Domain Set: A Report From The Psa Workshop At Omeract 2016., Ana-Maria Orbai, Maarten De Wit, Philip Mease, Kristina Callis Duffin, Musaab Elmamoun, William Tillett, Willemina Campbell, Oliver Fitzgerald, Dafna D Gladman, Niti Goel, Laure Gossec, Pil Hoejgaard, Ying Ying Leung, Chris Lindsay, Vibeke Strand, Désirée M Van Der Heijde, Bev Shea, Robin Christensen, Laura Coates, Lihi Eder, Neil Mchugh, Umut Kalyoncu, Ingrid Steinkoenig, Alexis Ogdie Oct 2017

Updating The Psoriatic Arthritis (Psa) Core Domain Set: A Report From The Psa Workshop At Omeract 2016., Ana-Maria Orbai, Maarten De Wit, Philip Mease, Kristina Callis Duffin, Musaab Elmamoun, William Tillett, Willemina Campbell, Oliver Fitzgerald, Dafna D Gladman, Niti Goel, Laure Gossec, Pil Hoejgaard, Ying Ying Leung, Chris Lindsay, Vibeke Strand, Désirée M Van Der Heijde, Bev Shea, Robin Christensen, Laura Coates, Lihi Eder, Neil Mchugh, Umut Kalyoncu, Ingrid Steinkoenig, Alexis Ogdie

Articles, Abstracts, and Reports

OBJECTIVE: To include the patient perspective in accordance with the Outcome Measures in Rheumatology (OMERACT) Filter 2.0 in the updated Psoriatic Arthritis (PsA) Core Domain Set for randomized controlled trials (RCT) and longitudinal observational studies (LOS).

METHODS: At OMERACT 2016, research conducted to update the PsA Core Domain Set was presented and discussed in breakout groups. The updated PsA Core Domain Set was voted on and endorsed by OMERACT participants.

RESULTS: We conducted a systematic literature review of domains measured in PsA RCT and LOS, and identified 24 domains. We conducted 24 focus groups with 130 patients from 7 countries …


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 Oct 2017

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 …


Editorial Perspective., Jens R Chapman Oct 2017

Editorial Perspective., Jens R Chapman

Articles, Abstracts, and Reports

No abstract provided.


The Ongoing Quest For The Holy Bone Graft Grail: Scientific Progress, Economic Bonanza, Or Quixotic Quagmire?, Jens R Chapman, Karsten Wiechert, Jeffrey C Wang Oct 2017

The Ongoing Quest For The Holy Bone Graft Grail: Scientific Progress, Economic Bonanza, Or Quixotic Quagmire?, Jens R Chapman, Karsten Wiechert, Jeffrey C Wang

Articles, Abstracts, and Reports

No abstract provided.


Efficacy Of Daclizumab Beta Versus Intramuscular Interferon Beta-1a On Disability Progression Across Patient Demographic And Disease Activity Subgroups In Decide., Stanley Cohan, Ludwig Kappos, Gavin Giovannoni, Heinz Wiendl, Krzysztof Selmaj, Eva Kubala Havrdová, John Rose, Steven Greenberg, Glenn Phillips, Wei Ma, Ping Wang, Gabriel Lima, Guido Sabatella Oct 2017

Efficacy Of Daclizumab Beta Versus Intramuscular Interferon Beta-1a On Disability Progression Across Patient Demographic And Disease Activity Subgroups In Decide., Stanley Cohan, Ludwig Kappos, Gavin Giovannoni, Heinz Wiendl, Krzysztof Selmaj, Eva Kubala Havrdová, John Rose, Steven Greenberg, Glenn Phillips, Wei Ma, Ping Wang, Gabriel Lima, Guido Sabatella

Articles, Abstracts, and Reports

BACKGROUND: Demonstration of clinical benefits on disability progression measures is an important attribute of effective multiple sclerosis (MS) treatments.

OBJECTIVE: Examine efficacy of daclizumab beta versus intramuscular (IM) interferon beta-1a on measures of disability progression in patient subgroups from DECIDE.

METHODS: Twenty-four-week confirmed disability progression (CDP), 24-week sustained worsening on a modified Multiple Sclerosis Functional Composite (MSFCS) where 3-Second Paced Auditory Serial Addition Test was replaced by Symbol Digit Modalities Test, and proportion of patients with clinically meaningful worsening in 29-Item Multiple Sclerosis Impact Scale physical impact subscale (MSIS-29 PHYS) score from baseline to week 96 were examined in the …


Angptl4 Promotes The Progression Of Cutaneous Melanoma To Brain Metastasis., Sivan Izraely, Shlomit Ben-Menachem, Orit Sagi-Assif, Tsipi Meshel, Diego M Marzese, Shuichi Ohe, Inna Zubrilov, Metsada Pasmanik-Chor, Dave S B Hoon, Isaac P Witz Sep 2017

Angptl4 Promotes The Progression Of Cutaneous Melanoma To Brain Metastasis., Sivan Izraely, Shlomit Ben-Menachem, Orit Sagi-Assif, Tsipi Meshel, Diego M Marzese, Shuichi Ohe, Inna Zubrilov, Metsada Pasmanik-Chor, Dave S B Hoon, Isaac P Witz

Articles, Abstracts, and Reports

In an ongoing effort to identify molecular determinants regulating melanoma brain metastasis, we previously identified Angiopoietin-like 4 (ANGPTL4) as a component of the molecular signature of such metastases. The aim of this study was to determine the functional significance of ANGPTL4 in the shaping of melanoma malignancy phenotype, especially in the establishment of brain metastasis. We confirmed that ANGPTL4 expression is significantly higher in cells metastasizing to the brain than in cells from the cutaneous (local) tumor from the same melanoma in a nude mouse xenograft model, and also in paired clinical specimens of melanoma metastases than in primary melanomas …


Predictors Of Responses To Immune Checkpoint Blockade In Advanced Melanoma., N Jacquelot, M P Roberti, D P Enot, S Rusakiewicz, N Ternès, S Jegou, D M Woods, A L Sodré, M Hansen, Y Meirow, M Sade-Feldman, A Burra, S S Kwek, C Flament, M Messaoudene, C P M Duong, L Chen, B S Kwon, A C Anderson, V K Kuchroo, B Weide, F Aubin, C Borg, S Dalle, O Beatrix, M Ayyoub, B Balme, G Tomasic, A M Di Giacomo, M Maio, D Schadendorf, I Melero, B Dréno, A Khammari, R Dummer, M Levesque, Yoshinobu Koguchi, L Fong, M Lotem, M Baniyash, H Schmidt, I M Svane, G Kroemer, A Marabelle, S Michiels, A Cavalcanti, M J Smyth, J S Weber, A M Eggermont, L Zitvogel Sep 2017

Predictors Of Responses To Immune Checkpoint Blockade In Advanced Melanoma., N Jacquelot, M P Roberti, D P Enot, S Rusakiewicz, N Ternès, S Jegou, D M Woods, A L Sodré, M Hansen, Y Meirow, M Sade-Feldman, A Burra, S S Kwek, C Flament, M Messaoudene, C P M Duong, L Chen, B S Kwon, A C Anderson, V K Kuchroo, B Weide, F Aubin, C Borg, S Dalle, O Beatrix, M Ayyoub, B Balme, G Tomasic, A M Di Giacomo, M Maio, D Schadendorf, I Melero, B Dréno, A Khammari, R Dummer, M Levesque, Yoshinobu Koguchi, L Fong, M Lotem, M Baniyash, H Schmidt, I M Svane, G Kroemer, A Marabelle, S Michiels, A Cavalcanti, M J Smyth, J S Weber, A M Eggermont, L Zitvogel

Articles, Abstracts, and Reports

Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs. Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB. Based on this assay, we retrospectively observed, in eight cohorts enrolling 190 MMel patients treated with ipilimumab, …


Neurosyphilis Increases Human Immunodeficiency Virus (Hiv)-Associated Central Nervous System Inflammation But Does Not Explain Cognitive Impairment In Hiv-Infected Individuals With Syphilis., Emily L Ho, Clare L Maxwell, Shelia B Dunaway, Sharon K Sahi, Lauren C Tantalo, Sheila A Lukehart, Christina M Marra Sep 2017

Neurosyphilis Increases Human Immunodeficiency Virus (Hiv)-Associated Central Nervous System Inflammation But Does Not Explain Cognitive Impairment In Hiv-Infected Individuals With Syphilis., Emily L Ho, Clare L Maxwell, Shelia B Dunaway, Sharon K Sahi, Lauren C Tantalo, Sheila A Lukehart, Christina M Marra

Articles, Abstracts, and Reports

Background: Individuals infected with human immunodeficiency virus (HIV) who have previously had syphilis may have cognitive impairment. We tested the hypothesis that neurosyphilis causes cognitive impairment in HIV by amplifying HIV-related central nervous system (CNS) inflammation.

Methods: HIV-infected participants enrolled in a study of cerebrospinal fluid (CSF) abnormalities in syphilis underwent the mental alternation test (MAT), venipuncture, and lumbar puncture. CSF concentrations of chemokine (C-X-C motif) ligand 10 (CXCL10), chemokine (C-C motif) ligand 2 (CCL2), and neurofilament light (NFL) were determined by commercial assays. The proportion of peripheral blood mononuclear cells (PBMCs) and of CSF white blood cells (WBCs) that …


A Global Staphylococcus Aureus Proteome Resource Applied To The In Vivo Characterization Of Host-Pathogen Interactions., Stephan Michalik, Maren Depke, Annette Murr, Manuela Gesell Salazar, Ulrike Kusebauch, Zhi Sun, Tanja C Meyer, Kristin Surmann, Henrike Pförtner, Petra Hildebrandt, Stefan Weiss, Laura Marcela Palma Medina, Melanie Gutjahr, Elke Hammer, Dörte Becher, Thomas Pribyl, Sven Hammerschmidt, Eric W Deutsch, Samuel L Bader, Michael Hecker, Robert L Moritz, Ulrike Mäder, Uwe Völker, Frank Schmidt Sep 2017

A Global Staphylococcus Aureus Proteome Resource Applied To The In Vivo Characterization Of Host-Pathogen Interactions., Stephan Michalik, Maren Depke, Annette Murr, Manuela Gesell Salazar, Ulrike Kusebauch, Zhi Sun, Tanja C Meyer, Kristin Surmann, Henrike Pförtner, Petra Hildebrandt, Stefan Weiss, Laura Marcela Palma Medina, Melanie Gutjahr, Elke Hammer, Dörte Becher, Thomas Pribyl, Sven Hammerschmidt, Eric W Deutsch, Samuel L Bader, Michael Hecker, Robert L Moritz, Ulrike Mäder, Uwe Völker, Frank Schmidt

Articles, Abstracts, and Reports

Data-independent acquisition mass spectrometry promises higher performance in terms of quantification and reproducibility compared to data-dependent acquisition mass spectrometry methods. To enable high-accuracy quantification of Staphylococcus aureus proteins, we have developed a global ion library for data-independent acquisition approaches employing high-resolution time of flight or Orbitrap instruments for this human pathogen. We applied this ion library resource to investigate the time-resolved adaptation of S. aureus to the intracellular niche in human bronchial epithelial cells and in a murine pneumonia model. In epithelial cells, abundance changes for more than 400 S. aureus proteins were quantified, revealing, e.g., the precise temporal regulation …


The Natural History Of Severe Acute Liver Injury., David G Koch, J L Speiser, V Durkalski, R J Fontana, T Davern, B Mcguire, R T Stravitz, A M Larson, I Liou, Oren K Fix, M L Schilsky, T Mccashland, J E Hay, N Murray, O S Shaikh, D Ganger, A Zaman, S B Han, R T Chung, R S Brown, S Munoz, K R Reddy, L Rossaro, R Satyanarayana, A J Hanje, J Olson, R M Subramanian, C Karvellas, B Hameed, A H Sherker, W M Lee, A Reuben Sep 2017

The Natural History Of Severe Acute Liver Injury., David G Koch, J L Speiser, V Durkalski, R J Fontana, T Davern, B Mcguire, R T Stravitz, A M Larson, I Liou, Oren K Fix, M L Schilsky, T Mccashland, J E Hay, N Murray, O S Shaikh, D Ganger, A Zaman, S B Han, R T Chung, R S Brown, S Munoz, K R Reddy, L Rossaro, R Satyanarayana, A J Hanje, J Olson, R M Subramanian, C Karvellas, B Hameed, A H Sherker, W M Lee, A Reuben

Articles, Abstracts, and Reports

OBJECTIVES: Acute liver failure (ALF) is classically defined by coagulopathy and hepatic encephalopathy (HE); however, acute liver injury (ALI), i.e., severe acute hepatocyte necrosis without HE, has not been carefully defined nor studied. Our aim is to describe the clinical course of specifically defined ALI, including the risk and clinical predictors of poor outcomes, namely progression to ALF, the need for liver transplantation (LT) and death.

METHODS: 386 subjects prospectively enrolled in the Acute Liver Failure Study Group registry between 1 September 2008 through 25 October 2013, met criteria for ALI: International Normalized Ratio (INR)≥2.0 and alanine aminotransferase (ALT)≥10 × …


Do We Really Understand Spine Treatments And Science Around The World?, Karsten Wiechert, Jeffrey C Wang, Jens R Chapman Sep 2017

Do We Really Understand Spine Treatments And Science Around The World?, Karsten Wiechert, Jeffrey C Wang, Jens R Chapman

Articles, Abstracts, and Reports

No abstract provided.


Sustained Efficacy, Safety And Patient-Reported Outcomes Of Certolizumab Pegol In Axial Spondyloarthritis: 4-Year Outcomes From Rapid-Axspa., Désirée Van Der Heijde, Maxime Dougados, Robert Landewé, Joachim Sieper, Walter P Maksymowych, Martin Rudwaleit, Filip Van Den Bosch, Jürgen Braun, Philip Mease, Alan J Kivitz, Jessica Walsh, Owen Davies, Lars Bauer, Bengt Hoepken, Luke Peterson, Atul Deodhar Sep 2017

Sustained Efficacy, Safety And Patient-Reported Outcomes Of Certolizumab Pegol In Axial Spondyloarthritis: 4-Year Outcomes From Rapid-Axspa., Désirée Van Der Heijde, Maxime Dougados, Robert Landewé, Joachim Sieper, Walter P Maksymowych, Martin Rudwaleit, Filip Van Den Bosch, Jürgen Braun, Philip Mease, Alan J Kivitz, Jessica Walsh, Owen Davies, Lars Bauer, Bengt Hoepken, Luke Peterson, Atul Deodhar

Articles, Abstracts, and Reports

Objective: The aim was to assess the long-term safety and efficacy of certolizumab pegol over 4 years of continuous treatment in patients with axial spondyloarthritis (axSpA), including both AS and non-radiographic (nr-) axSpA.

Methods: RAPID-axSpA was a phase 3 randomized trial, double blind and placebo controlled to week 24, dose blind to week 48 and open label to week 204. Patients had a clinical diagnosis of axSpA, meeting Assessment of SpondyloArthritis international Society (ASAS) criteria, and had active disease. The assessed outcomes included ASAS20, ASAS40, AS DAS (ASDAS), BASDAI, BASFI and BASMI scores, along with selected measures of remission. Further …


The Prognostic Importance Of Scalp Location In Primary Head And Neck Melanoma., Junko Ozao-Choy, Daniel W Nelson, Jason Hiles, Stacey L Stern, Jeong Lim Yoon, Myung Shin Sim, Mark Faries Sep 2017

The Prognostic Importance Of Scalp Location In Primary Head And Neck Melanoma., Junko Ozao-Choy, Daniel W Nelson, Jason Hiles, Stacey L Stern, Jeong Lim Yoon, Myung Shin Sim, Mark Faries

Articles, Abstracts, and Reports

BACKGROUND AND OBJECTIVES: For patients with cutaneous melanoma, primary tumors located in the head and neck is associated with poor outcomes. The reason for this difference and whether it is applicable to all locations within the head and neck remains unclear. We hypothesized that scalp melanoma is uniquely distinguished from other anatomic sites and is independently responsible for the poor prognosis of head and neck melanoma.

METHODS: Query and analysis of a prospectively maintained melanoma database of all patients treated for primary cutaneous melanoma from 1971 to 2010.

RESULTS: Of 11 384 patients identified, 7% (n = 799) of lesions …


Effects Of Socioeconomic Status On Children With Well-Differentiated Thyroid Cancer., Evan F Garner, Ilan I Maizlin, Matthew B Dellinger, Kenneth W Gow, Melanie Goldfarb, Adam B Goldin, John J Doski, Monica Langer, Jed G Nuchtern, Sanjeev A Vasudevan, Mehul V Raval, Elizabeth A Beierle Sep 2017

Effects Of Socioeconomic Status On Children With Well-Differentiated Thyroid Cancer., Evan F Garner, Ilan I Maizlin, Matthew B Dellinger, Kenneth W Gow, Melanie Goldfarb, Adam B Goldin, John J Doski, Monica Langer, Jed G Nuchtern, Sanjeev A Vasudevan, Mehul V Raval, Elizabeth A Beierle

Articles, Abstracts, and Reports

BACKGROUND: Well-differentiated thyroid cancer is the most common endocrine malignancy in children. Adult literature has demonstrated socioeconomic disparities in patients undergoing thyroidectomy, but the effects of socioeconomic status on the management of pediatric well-differentiated thyroid cancer remains poorly understood.

METHODS: Patients ≤21 years of age with well-differentiated thyroid cancer remains were reviewed from the National Cancer Data Base. Three socioeconomic surrogate variables were identified: insurance type, median income, and educational quartile. Tumor characteristics, diagnostic intervals, and clinical outcomes were compared within each socioeconomic surrogate variable.

RESULTS: A total of 9,585 children with well-differentiated thyroid cancer remains were reviewed. In multivariate …


Efficacy And Safety Of Abatacept, A T-Cell Modulator, In A Randomised, Double-Blind, Placebo-Controlled, Phase Iii Study In Psoriatic Arthritis., Philip Mease, Alice B Gottlieb, Désirée Van Der Heijde, Oliver Fitzgerald, Alyssa Johnsen, Marleen Nys, Subhashis Banerjee, Dafna D Gladman Sep 2017

Efficacy And Safety Of Abatacept, A T-Cell Modulator, In A Randomised, Double-Blind, Placebo-Controlled, Phase Iii Study In Psoriatic Arthritis., Philip Mease, Alice B Gottlieb, Désirée Van Der Heijde, Oliver Fitzgerald, Alyssa Johnsen, Marleen Nys, Subhashis Banerjee, Dafna D Gladman

Articles, Abstracts, and Reports

OBJECTIVES: To assess the efficacy and safety of abatacept, a selective T-cell costimulation modulator, in a phase III study in psoriatic arthritis (PsA).

METHODS: This study randomised patients (1:1) with active PsA (~60% with prior exposure to a tumour necrosis factor inhibitor) to blinded weekly subcutaneous abatacept 125 mg (n=213) or placebo (n=211) for 24 weeks, followed by open-label subcutaneous abatacept. Patients without ≥20% improvement in joint counts at week 16 were switched to open-label abatacept. The primary end point was the proportion of patients with ≥20% improvement in the American College of Rheumatology (ACR20) criteria at week 24.

RESULTS: …


Anterior Inferior Cerebellar Arteries Juxtaposed With The Internal Acoustic Meatus And Their Relationship To The Cranial Nerve Vii/Viii Complex., Fernando Alonso, Mohammad W Kassem, Joe Iwanaga, Rod J Oskouian, Marios Loukas, Amin Demerdash, R Shane Tubbs Aug 2017

Anterior Inferior Cerebellar Arteries Juxtaposed With The Internal Acoustic Meatus And Their Relationship To The Cranial Nerve Vii/Viii Complex., Fernando Alonso, Mohammad W Kassem, Joe Iwanaga, Rod J Oskouian, Marios Loukas, Amin Demerdash, R Shane Tubbs

Articles, Abstracts, and Reports

Vascular loops in the cerebellopontine angle (CPA) and their relationship to cranial nerves have been used to explain neurological symptoms. The anterior inferior cerebellar artery (AICA) has variable branches producing vascular loops that can compress the facial cranial nerve (CN) VII and vestibulocochlear (CN VIII) nerves. AICA compression of the facial-vestibulocochlear nerve complex can lead to various clinical presentations, including hemifacial spasm (HFS), tinnitus, and hemiataxia. The formation of arterial loops inside or outside of the internal auditory meatus (IAM) can cause abutment or compression of CN VII and CN VIII. Twenty-five (50 sides) fresh adult cadavers underwent dissection of …


Chiari I Malformation And Spinal Cord Ischemia In A Cadaver., Faizullah Mashriqi, Marios Loukas, Rod J Oskouian, Anthony V D'Antoni, R Shane Tubbs Aug 2017

Chiari I Malformation And Spinal Cord Ischemia In A Cadaver., Faizullah Mashriqi, Marios Loukas, Rod J Oskouian, Anthony V D'Antoni, R Shane Tubbs

Articles, Abstracts, and Reports

With advanced imaging, the Chiari I malformation (CIM) is more frequently diagnosed than in the past when this entity was identified most commonly at autopsy. Herein, we report the rare case of an adult cadaver found not only to have CIM but also adjacent spinal cord ischemia. This case is discussed in the context of chronic compression of the spinal cord by a CIM and the need for close monitoring of these patients.


Epigenetic Regulation Of Kpc1 Ubiquitin Ligase Affects The Nf-Κb Pathway In Melanoma., Yuuki Iida, Aaron Ciechanover, Diego M Marzese, Keisuke Hata, Matias Bustos, Shigeshi Ono, Jinhua Wang, Matthew P Salomon, Kevin Tran, Stella Lam, Sandy Hsu, Nellie Nelson, Yelena Kravtsova-Ivantsiv, Gordon B Mills, Michael A Davies, Dave S B Hoon Aug 2017

Epigenetic Regulation Of Kpc1 Ubiquitin Ligase Affects The Nf-Κb Pathway In Melanoma., Yuuki Iida, Aaron Ciechanover, Diego M Marzese, Keisuke Hata, Matias Bustos, Shigeshi Ono, Jinhua Wang, Matthew P Salomon, Kevin Tran, Stella Lam, Sandy Hsu, Nellie Nelson, Yelena Kravtsova-Ivantsiv, Gordon B Mills, Michael A Davies, Dave S B Hoon

Articles, Abstracts, and Reports

Purpose: Abnormal activation of the NF-κB pathway induces a more aggressive phenotype of cutaneous melanoma. Understanding the mechanisms involved in melanoma NF-κB activation may identify novel targets for this pathway. KPC1, an E3 ubiquitin ligase, is a regulator of the NF-κB pathway. The objective of this study was to investigate the mechanisms regulating KPC1 expression and its clinical impact in melanoma.Experimental Design: The clinical impact of KPC1 expression and its epigenetic regulation were assessed in large cohorts of clinically well-annotated melanoma tissues (tissue microarrays; n = 137, JWCI cohort; n = 40) and The Cancer Genome Atlas database (TCGA …


Integrative Analysis Identifies Four Molecular And Clinical Subsets In Uveal Melanoma., A Gordon Robertson, Juliann Shih, Christina Yau, Ewan A Gibb, Junna Oba, Karen L Mungall, Julian M Hess, Vladislav Uzunangelov, Vonn Walter, Ludmila Danilova, Tara M Lichtenberg, Melanie Kucherlapati, Patrick K Kimes, Ming Tang, Alexander Penson, Ozgun Babur, Rehan Akbani, Christopher A Bristow, Katherine A Hoadley, Lisa Iype, Matthew T Chang, Andrew D Cherniack, Christopher Benz, Gordon B Mills, Roel G W Verhaak, Klaus G Griewank, Ina Felau, Jean C Zenklusen, Jeffrey E Gershenwald, Lynn Schoenfield, Alexander J Lazar, Mohamed H Abdel-Rahman, Sergio Roman-Roman, Marc-Henri Stern, Colleen M Cebulla, Michelle D Williams, Martine J Jager, Sarah E Coupland, Bita Esmaeli, Cyriac Kandoth, Scott E Woodman Aug 2017

Integrative Analysis Identifies Four Molecular And Clinical Subsets In Uveal Melanoma., A Gordon Robertson, Juliann Shih, Christina Yau, Ewan A Gibb, Junna Oba, Karen L Mungall, Julian M Hess, Vladislav Uzunangelov, Vonn Walter, Ludmila Danilova, Tara M Lichtenberg, Melanie Kucherlapati, Patrick K Kimes, Ming Tang, Alexander Penson, Ozgun Babur, Rehan Akbani, Christopher A Bristow, Katherine A Hoadley, Lisa Iype, Matthew T Chang, Andrew D Cherniack, Christopher Benz, Gordon B Mills, Roel G W Verhaak, Klaus G Griewank, Ina Felau, Jean C Zenklusen, Jeffrey E Gershenwald, Lynn Schoenfield, Alexander J Lazar, Mohamed H Abdel-Rahman, Sergio Roman-Roman, Marc-Henri Stern, Colleen M Cebulla, Michelle D Williams, Martine J Jager, Sarah E Coupland, Bita Esmaeli, Cyriac Kandoth, Scott E Woodman

Articles, Abstracts, and Reports

Comprehensive multiplatform analysis of 80 uveal melanomas (UM) identifies four molecularly distinct, clinically relevant subtypes: two associated with poor-prognosis monosomy 3 (M3) and two with better-prognosis disomy 3 (D3). We show that BAP1 loss follows M3 occurrence and correlates with a global DNA methylation state that is distinct from D3-UM. Poor-prognosis M3-UM divide into subsets with divergent genomic aberrations, transcriptional features, and clinical outcomes. We report change-of-function SRSF2 mutations. Within D3-UM, EIF1AX- and SRSF2/SF3B1-mutant tumors have distinct somatic copy number alterations and DNA methylation profiles, providing insight into the biology of these low- versus intermediate-risk clinical mutation subtypes.


Therapeutic Considerations For Antihyperglycemic Agents In Diabetic Kidney Disease., Joshua J Neumiller, Radica Alicic, Katherine Tuttle Aug 2017

Therapeutic Considerations For Antihyperglycemic Agents In Diabetic Kidney Disease., Joshua J Neumiller, Radica Alicic, Katherine Tuttle

Articles, Abstracts, and Reports

Diabetic kidney disease is among the most frequent complications of diabetes, with approximately 50% of patients with ESRD attributed to diabetes in developed countries. Although intensive glycemic management has been shown to delay the onset and progression of increased urinary albumin excretion and reduced GFR in patients with diabetes, conservative dose selection and adjustment of antihyperglycemic medications are necessary to balance glycemic control with safety. A growing body of literature is providing valuable insight into the cardiovascular and renal safety and efficacy of newer antihyperglycemic medications in the dipeptidyl peptidase-4 inhibitor, glucagon-like peptide-1 receptor agonist, and sodium-glucose cotransporter 2 inhibitor …


Incidence, Positional Distribution, Severity, And Time Missed In Medial Collateral Ligament Injuries Of The Knee In Ncaa Division I Football Athletes., Ali R Motamedi, Anirudh K Gowd, Alireza K Nazemi, Stephen T Gardner, Caleb J Behrend Aug 2017

Incidence, Positional Distribution, Severity, And Time Missed In Medial Collateral Ligament Injuries Of The Knee In Ncaa Division I Football Athletes., Ali R Motamedi, Anirudh K Gowd, Alireza K Nazemi, Stephen T Gardner, Caleb J Behrend

Articles, Abstracts, and Reports

Introduction: We studied injury to the medial collateral ligament (MCL) in National Collegiate Athletic Association (NCAA) Division I football players, their incidence, magnitude of injury, distribution by position, and missed time, which has not previously been described in a consecutive series.

Methods: The knee injuries sustained in 163 consecutive NCAA Division I collegiate football players at our institution were evaluated over a span of 6 years.

Results: The incidence of MCL injuries with any knee injury was 29% (47 of 163). Of 47 MCL injuries, 34% occurred in defensive linemen and 29% in offensive linemen. The average days missed by …


High Agreement Between Benchtop And Point-Of-Care Dipcard Tests For Ethyl Glucuronide., Emily Leickly, Jordan Skalisky, Sterling Mcpherson, Michael F Orr, Michael G Mcdonell Aug 2017

High Agreement Between Benchtop And Point-Of-Care Dipcard Tests For Ethyl Glucuronide., Emily Leickly, Jordan Skalisky, Sterling Mcpherson, Michael F Orr, Michael G Mcdonell

Articles, Abstracts, and Reports

No abstract provided.


Surgical Implications And Variability In The Use Of The Flat Epithelial Atypia Diagnosis On Breast Biopsy Specimens., Laura S Samples, Mara H Rendi, Paul D Frederick, Kimberly H Allison, Heidi D Nelson, Thomas R Morgan, Donald L Weaver, Joann G Elmore Aug 2017

Surgical Implications And Variability In The Use Of The Flat Epithelial Atypia Diagnosis On Breast Biopsy Specimens., Laura S Samples, Mara H Rendi, Paul D Frederick, Kimberly H Allison, Heidi D Nelson, Thomas R Morgan, Donald L Weaver, Joann G Elmore

Articles, Abstracts, and Reports

OBJECTIVES: Flat epithelial atypia (FEA) is a relatively new diagnostic term with uncertain clinical significance for surgical management. Any implied risk of invasive breast cancer associated with FEA is contingent upon diagnostic reproducibility, yet little is known regarding its use.

MATERIALS AND METHODS: Pathologists in the Breast Pathology Study interpreted one of four 60-case test sets, one slide per case, constructed from 240 breast biopsy specimens. An electronic data form with standardized diagnostic categories was used; participants were instructed to indicate all diagnoses present. We assessed participants' use of FEA as a diagnostic term within: 1) each test set; 2) …


A Tnf-Jnk-Axl-Erk Signaling Axis Mediates Primary Resistance To Egfr Inhibition In Glioblastoma., Gao Guo, Ke Gong, Sonia Ali, Neha Ali, Shahzad Shallwani, Kimmo J Hatanpaa, Edward Pan, Bruce Mickey, Sandeep Burma, David H Wang, Santosh Kesari, Jann N Sarkaria, Dawen Zhao, Amyn A Habib Aug 2017

A Tnf-Jnk-Axl-Erk Signaling Axis Mediates Primary Resistance To Egfr Inhibition In Glioblastoma., Gao Guo, Ke Gong, Sonia Ali, Neha Ali, Shahzad Shallwani, Kimmo J Hatanpaa, Edward Pan, Bruce Mickey, Sandeep Burma, David H Wang, Santosh Kesari, Jann N Sarkaria, Dawen Zhao, Amyn A Habib

Articles, Abstracts, and Reports

Aberrant epidermal growth factor receptor (EGFR) signaling is widespread in cancer, making the EGFR an important target for therapy. EGFR gene amplification and mutation are common in glioblastoma (GBM), but EGFR inhibition has not been effective in treating this tumor. Here we propose that primary resistance to EGFR inhibition in glioma cells results from a rapid compensatory response to EGFR inhibition that mediates cell survival. We show that in glioma cells expressing either EGFR wild type or the mutant EGFRvIII, EGFR inhibition triggers a rapid adaptive response driven by increased tumor necrosis factor (TNF) secretion, which leads to activation in …


Hypomethylation Of Cntfrα Is Associated With Proliferation And Poor Prognosis In Lower Grade Gliomas., Kun Fan, Xiaowen Wang, Jingwen Zhang, Romela Irene Ramos, Haibo Zhang, Chunjie Li, Dan Ye, Jiansheng Kang, Diego M Marzese, Dave S B Hoon, Wei Hua Aug 2017

Hypomethylation Of Cntfrα Is Associated With Proliferation And Poor Prognosis In Lower Grade Gliomas., Kun Fan, Xiaowen Wang, Jingwen Zhang, Romela Irene Ramos, Haibo Zhang, Chunjie Li, Dan Ye, Jiansheng Kang, Diego M Marzese, Dave S B Hoon, Wei Hua

Articles, Abstracts, and Reports

Ciliary neurotrophic factor receptor α subunit (CNTFRα) and CNTF play important roles in neuron survival, glial differentiation and brain tumor growth. However, the molecular mechanisms of CNTFRα regulation and its clinical significance in glioma remain largely unknown. Here, we found CNTFRα was overexpressed in lower grade gliomas (LGG) compared with glioblastoma (GBM) and normal brain specimens in TCGA datasets and in an independent cohort. Bioinformatics analysis revealed a CpG shore of the CNTFRα gene regulated its mRNA expression in TCGA datasets. This observation was further validated with clinical specimens and functionally verified using demethylating agents. Additionally, we observed that independent …


Impact Of Home Visit Capacity On Genetic Association Studies Of Late-Onset Alzheimer's Disease., David W Fardo, Laura E Gibbons, Shubhabrata Mukherjee, M Maria Glymour, Wayne Mccormick, Susan M Mccurry, James D Bowen, Eric B Larson, Paul K Crane Aug 2017

Impact Of Home Visit Capacity On Genetic Association Studies Of Late-Onset Alzheimer's Disease., David W Fardo, Laura E Gibbons, Shubhabrata Mukherjee, M Maria Glymour, Wayne Mccormick, Susan M Mccurry, James D Bowen, Eric B Larson, Paul K Crane

Articles, Abstracts, and Reports

INTRODUCTION: Findings for genetic correlates of late-onset Alzheimer's disease (LOAD) in studies that rely solely on clinic visits may differ from those with capacity to follow participants unable to attend clinic visits.

METHODS: We evaluated previously identified LOAD-risk single nucleotide variants in the prospective Adult Changes in Thought study, comparing hazard ratios (HRs) estimated using the full data set of both in-home and clinic visits (n = 1697) to HRs estimated using only data that were obtained from clinic visits (n = 1308). Models were adjusted for age, sex, principal components to account for ancestry, and additional health indicators.

RESULTS: …


The Impact Of Smoking On Sentinel Node Metastasis Of Primary Cutaneous Melanoma., Maris S Jones, Peter C Jones, Stacey L Stern, David Elashoff, Dave S B Hoon, John Thompson, Nicola Mozzillo, Omgo E Nieweg, Dirk Noyes, Harald J Hoekstra, Jonathan S Zager, Daniel F Roses, Alessandro Testori, Brendon J Coventry, Mark B Smithers, Robert Andtbacka, Doreen Agnese, Erwin Schultz, Eddy C Hsueh, Mark Kelley, Schlomo Schneebaum, Lisa Jacobs, Tawnya Bowles, Mohammed Kashani-Sabet, Douglas Johnson, Mark B Faries Aug 2017

The Impact Of Smoking On Sentinel Node Metastasis Of Primary Cutaneous Melanoma., Maris S Jones, Peter C Jones, Stacey L Stern, David Elashoff, Dave S B Hoon, John Thompson, Nicola Mozzillo, Omgo E Nieweg, Dirk Noyes, Harald J Hoekstra, Jonathan S Zager, Daniel F Roses, Alessandro Testori, Brendon J Coventry, Mark B Smithers, Robert Andtbacka, Doreen Agnese, Erwin Schultz, Eddy C Hsueh, Mark Kelley, Schlomo Schneebaum, Lisa Jacobs, Tawnya Bowles, Mohammed Kashani-Sabet, Douglas Johnson, Mark B Faries

Articles, Abstracts, and Reports

BACKGROUND: Although a well-established causative relationship exists between smoking and several epithelial cancers, the association of smoking with metastatic progression in melanoma is not well studied. We hypothesized that smokers would be at increased risk for melanoma metastasis as assessed by sentinel lymph node (SLN) biopsy.

METHODS: Data from the first international Multicenter Selective Lymphadenectomy Trial (MSLT-I) and the screening-phase of the second trial (MSLT-II) were analyzed to determine the association of smoking with clinicopathologic variables and SLN metastasis.

RESULTS: Current smoking was strongly associated with SLN metastasis (p = 0.004), even after adjusting for other predictors of metastasis. Among …


Role Of Physical Activity For Weight Loss And Weight Maintenance., Carla E Cox Aug 2017

Role Of Physical Activity For Weight Loss And Weight Maintenance., Carla E Cox

Articles, Abstracts, and Reports

This article reviews the impact of exercise on weight loss and weight maintenance and the possible reasons that weight loss outcomes resulting from exercise are not consistently realized.


Quantitative Anterior And Posterior Clinoidectomy Analysis And Mobilization Of The Oculomotor Nerve During Surgical Exposure Of The Basilar Apex Using Frameless Stereotaxis., Aclan Dogan, Justin S Cetas, Gregory J Anderson, Andy Rekito, Johnny B Delashaw Aug 2017

Quantitative Anterior And Posterior Clinoidectomy Analysis And Mobilization Of The Oculomotor Nerve During Surgical Exposure Of The Basilar Apex Using Frameless Stereotaxis., Aclan Dogan, Justin S Cetas, Gregory J Anderson, Andy Rekito, Johnny B Delashaw

Articles, Abstracts, and Reports

No abstract provided.