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Articles 571 - 600 of 858
Full-Text Articles in Medical Specialties
Secukinumab Versus Adalimumab For Psoriatic Arthritis: Comparative Effectiveness Up To 48 Weeks Using A Matching-Adjusted Indirect Comparison., Peter Nash, Iain B Mcinnes, Philip Mease, Howard Thom, Matthias Hunger, Andreas Karabis, Kunal Gandhi, Shephard Mpofu, Steffen M Jugl
Secukinumab Versus Adalimumab For Psoriatic Arthritis: Comparative Effectiveness Up To 48 Weeks Using A Matching-Adjusted Indirect Comparison., Peter Nash, Iain B Mcinnes, Philip Mease, Howard Thom, Matthias Hunger, Andreas Karabis, Kunal Gandhi, Shephard Mpofu, Steffen M Jugl
Articles, Abstracts, and Reports
INTRODUCTION: Secukinumab and adalimumab are approved for adults with active psoriatic arthritis (PsA). In the absence of direct randomized controlled trial (RCT) data, matching-adjusted indirect comparison can estimate the comparative effectiveness in anti-tumor necrosis factor (TNF)-naïve populations.
METHODS: Individual patient data from the FUTURE 2 RCT (secukinumab vs. placebo; N = 299) were adjusted to match baseline characteristics of the ADEPT RCT (adalimumab vs. placebo; N = 313). Logistic regression determined adjustment weights for age, body weight, sex, race, methotrexate use, psoriasis affecting ≥ 3% of body surface area, Psoriasis Area and Severity Index score, Health Assessment Questionnaire Disability Index …
Telesurgery: Past, Present, And Future., Paul J Choi, Rod J Oskouian, R Shane Tubbs
Telesurgery: Past, Present, And Future., Paul J Choi, Rod J Oskouian, R Shane Tubbs
Articles, Abstracts, and Reports
Telesurgery uses wireless networking and robotic technology to allow surgeons to operate on patients who are distantly located. This technology not only benefits today's shortage of surgeons, but it also eliminates geographical barriers that prevent timely and high-quality surgical intervention, financial burden, complications, and often risky long-distance travel. The system also provides improved surgical accuracy and ensures the safety of surgeons. In this paper, we describe the current trend of telesurgery's innovative developments and its future.
Extreme Lateral Interbody Fusion Complicated By Fungal Osteomyelitis: Case Report And Quick Review Of The Literature., Ronen Blecher, Emre Yilmaz, Marc Moisi, Rod J Oskouian, Jens Chapman
Extreme Lateral Interbody Fusion Complicated By Fungal Osteomyelitis: Case Report And Quick Review Of The Literature., Ronen Blecher, Emre Yilmaz, Marc Moisi, Rod J Oskouian, Jens Chapman
Articles, Abstracts, and Reports
The authors describe a 67-year-old man with a prior history of alcohol abuse who presented with a complaint of worsening low back pain. Four months prior to his presentation, the patient had undergone extreme lateral interbody fusion (XLIF) of his lumbar 3-4 segment for the treatment of his chronic low back and legs pain. Imaging revealed a loosening of his interbody fusion implant on top of his prior lumbar spine instrumentation. In surgery, the removal of his loose implant was followed by decompression, the stabilization of the collapsed segment, and the implant of antibiotic-impregnated polymethyl-methacrylate (PMMA) spacer and beads. At …
Substance-Induced Anxiety Disorder After One Dose Of 3,4-Methylenedioxymethamphetamine: A Case Report., Kaeley Kaplan, Fiona Kurtz, Kelly Serafini
Substance-Induced Anxiety Disorder After One Dose Of 3,4-Methylenedioxymethamphetamine: A Case Report., Kaeley Kaplan, Fiona Kurtz, Kelly Serafini
Articles, Abstracts, and Reports
BACKGROUND: In this report, we describe a case of a patient with substance-induced anxiety disorder occurring after a single dose of 3,4-methylenedioxymethamphetamine. Furthermore, we describe the use and efficacy of the Primary Care Behavioral Health model, a collaborative approach to integrative primary mental health care, in evaluating and treating this rare mental health disorder.
CASE PRESENTATION: Three days following ingestion of one dose of 3,4-methylenedioxymethamphetamine, a 35-year-old Hispanic man with no significant prior mental health history and no history of prior 3,4-methylenedioxymethamphetamine use presented to our hospital with severe, acute anxiety and panic symptoms. He was initially treated with a …
Variant Distal Ulnar Nerve Loop: A Previously Undescribed Anatomical Finding., Mayank Patel, Joe Iwanaga, Rod J Oskouian, R Shane Tubbs
Variant Distal Ulnar Nerve Loop: A Previously Undescribed Anatomical Finding., Mayank Patel, Joe Iwanaga, Rod J Oskouian, R Shane Tubbs
Articles, Abstracts, and Reports
A previously undescribed variant ulnar nerve loop was discovered during the routine anatomic forearm and hand dissection of an adult female. The major finding was that of a large loop traveling around the distal tendon of the flexor carpi ulnaris. The variation presented here appears to be unique. The exact function of such derailed anatomy is not clear but, if found during surgery, might confound normal dissection methods or, when present, could result in varied clinical presentations regarding the sensory or motor examination of the hand.
Tumor Cure By Radiation Therapy And Checkpoint Inhibitors Depends On Pre-Existing Immunity., Marka R Crittenden, Lauren Zebertavage, Gwen Kramer, Shelly Bambina, David Friedman, Victoria Troesch, Tiffany Blair, Jason R Baird, Alejandro F Alice, Michael J Gough
Tumor Cure By Radiation Therapy And Checkpoint Inhibitors Depends On Pre-Existing Immunity., Marka R Crittenden, Lauren Zebertavage, Gwen Kramer, Shelly Bambina, David Friedman, Victoria Troesch, Tiffany Blair, Jason R Baird, Alejandro F Alice, Michael J Gough
Articles, Abstracts, and Reports
Radiation therapy is a source of tumor antigen release that has the potential to serve as an endogenous tumor vaccination event. In preclinical models radiation therapy synergizes with checkpoint inhibitors to cure tumors via CD8 T cell responses. To evaluate the immune response initiated by radiation therapy, we used a range of approaches to block the pre-existing immune response artifact initiated by tumor implantation. We demonstrate that blocking immune responses at tumor implantation blocks development of a tumor-resident antigen specific T cell population and prevents tumor cure by radiation therapy combined with checkpoint immunotherapy. These data demonstrate that this treatment …
Gastric Hibernoma: A Novel Location And Presentation Of A Rare Tumor., Shane P Smith, Andrew F Feczko, Matias Mihura, Jey-Hsin Chen, Alexander S Farivar
Gastric Hibernoma: A Novel Location And Presentation Of A Rare Tumor., Shane P Smith, Andrew F Feczko, Matias Mihura, Jey-Hsin Chen, Alexander S Farivar
Articles, Abstracts, and Reports
We present a case of gastric hibernoma, an unusual tumor with a location novel to the literature. A 39-year-old female presented with one year of upper gastrointestinal bleeding and dysphagia. Gastroenterology performed an esophagogastroduodenoscopy with ultrasound and identified a 6 cm mass within the muscularis propria of the antrum. Computed tomography demonstrated a 9.7 × 7.8 × 4.8 cm
Extracellular Vesicle Rnas Reflect Placenta Dysfunction And Are A Biomarker Source For Preterm Labour., Shannon Fallen, David Baxter, Xiaogang Wu, Taek-Kyun Kim, Oksana Shynlova, Min Young Lee, Kelsey Scherler, Stephen Lye, Leroy Hood, Kai Wang
Extracellular Vesicle Rnas Reflect Placenta Dysfunction And Are A Biomarker Source For Preterm Labour., Shannon Fallen, David Baxter, Xiaogang Wu, Taek-Kyun Kim, Oksana Shynlova, Min Young Lee, Kelsey Scherler, Stephen Lye, Leroy Hood, Kai Wang
Articles, Abstracts, and Reports
Preterm birth (PTB) can lead to lifelong complications and challenges. Identifying and monitoring molecular signals in easily accessible biological samples that can diagnose or predict the risk of preterm labour (PTL) in pregnant women will reduce or prevent PTBs. A number of studies identified putative biomarkers for PTL including protein, miRNA and hormones from various body fluids. However, biomarkers identified from these studies usually lack consistency and reproducibility. Extracellular vesicles (EVs) in circulation have gained significant interest in recent years as these vesicles may be involved in cell-cell communication. We have used an improved small RNA library construction protocol and …
Alt-803, An Il-15 Superagonist, In Combination With Nivolumab In Patients With Metastatic Non-Small Cell Lung Cancer: A Non-Randomised, Open-Label, Phase 1b Trial., John M Wrangle, Vamsidhar Velcheti, Manish R Patel, Elizabeth Garrett-Mayer, Elizabeth G Hill, James G Ravenel, Jeffrey S Miller, Mohammad Farhad, Kate Anderton, Kathryn Lindsey, Michele Taffaro-Neskey, Carol Sherman, Samantha Suriano, Marzena Swiderska-Syn, Amy Sion, Joni Harris, Andie R Edwards, Julie A Rytlewski, Catherine M Sanders, Erik C Yusko, Mark D Robinson, Carsten Krieg, William L Redmond, Jack O Egan, Peter R Rhode, Emily K Jeng, Amy D Rock, Hing C Wong, Mark P Rubinstein
Alt-803, An Il-15 Superagonist, In Combination With Nivolumab In Patients With Metastatic Non-Small Cell Lung Cancer: A Non-Randomised, Open-Label, Phase 1b Trial., John M Wrangle, Vamsidhar Velcheti, Manish R Patel, Elizabeth Garrett-Mayer, Elizabeth G Hill, James G Ravenel, Jeffrey S Miller, Mohammad Farhad, Kate Anderton, Kathryn Lindsey, Michele Taffaro-Neskey, Carol Sherman, Samantha Suriano, Marzena Swiderska-Syn, Amy Sion, Joni Harris, Andie R Edwards, Julie A Rytlewski, Catherine M Sanders, Erik C Yusko, Mark D Robinson, Carsten Krieg, William L Redmond, Jack O Egan, Peter R Rhode, Emily K Jeng, Amy D Rock, Hing C Wong, Mark P Rubinstein
Articles, Abstracts, and Reports
BACKGROUND: Immunotherapy with PD-1 or PD-L1 blockade fails to induce a response in about 80% of patients with unselected non-small cell lung cancer (NSCLC), and many of those who do initially respond then develop resistance to treatment. Agonists that target the shared interleukin-2 (IL-2) and IL-15Rβγ pathway have induced complete and durable responses in some cancers, but no studies have been done to assess the safety or efficacy of these agonists in combination with anti-PD-1 immunotherapy. We aimed to define the safety, tolerability, and activity of this drug combination in patients with NSCLC.
METHODS: In this non-randomised, open-label, phase 1b …
Population-Specific Genetic Modification Of Huntington's Disease In Venezuela., Michael J Chao, Kyung-Hee Kim, Jun Wan Shin, Diane Lucente, Vanessa C Wheeler, Hong Li, Jared C Roach, Leroy Hood, Nancy S Wexler, Laura B Jardim, Peter Holmans, Lesley Jones, Michael Orth, Seung Kwak, Marcy E Macdonald, James F Gusella, Jong-Min Lee
Population-Specific Genetic Modification Of Huntington's Disease In Venezuela., Michael J Chao, Kyung-Hee Kim, Jun Wan Shin, Diane Lucente, Vanessa C Wheeler, Hong Li, Jared C Roach, Leroy Hood, Nancy S Wexler, Laura B Jardim, Peter Holmans, Lesley Jones, Michael Orth, Seung Kwak, Marcy E Macdonald, James F Gusella, Jong-Min Lee
Articles, Abstracts, and Reports
Modifiers of Mendelian disorders can provide insights into disease mechanisms and guide therapeutic strategies. A recent genome-wide association (GWA) study discovered genetic modifiers of Huntington's disease (HD) onset in Europeans. Here, we performed whole genome sequencing and GWA analysis of a Venezuelan HD cluster whose families were crucial for the original mapping of the HD gene defect. The Venezuelan HD subjects develop motor symptoms earlier than their European counterparts, implying the potential for population-specific modifiers. The main Venezuelan HD family inherits HTT haplotype hap.03, which differs subtly at the sequence level from European HD hap.03, suggesting a different ancestral origin …
A Randomized, Placebo-Controlled Trial Of Cenicriviroc For Treatment Of Nonalcoholic Steatohepatitis With Fibrosis., Scott L Friedman, Vlad Ratziu, Stephen A Harrison, Manal F Abdelmalek, Guruprasad P Aithal, Juan Caballeria, Sven Francque, Geoffrey Farrell, Kris V Kowdley, Antonio Craxi, Krzysztof Simon, Laurent Fischer, Liza Melchor-Khan, Jeffrey Vest, Brian L Wiens, Pamela Vig, Star Seyedkazemi, Zachary Goodman, Vincent Wai-Sun Wong, Rohit Loomba, Frank Tacke, Arun Sanyal, Eric Lefebvre
A Randomized, Placebo-Controlled Trial Of Cenicriviroc For Treatment Of Nonalcoholic Steatohepatitis With Fibrosis., Scott L Friedman, Vlad Ratziu, Stephen A Harrison, Manal F Abdelmalek, Guruprasad P Aithal, Juan Caballeria, Sven Francque, Geoffrey Farrell, Kris V Kowdley, Antonio Craxi, Krzysztof Simon, Laurent Fischer, Liza Melchor-Khan, Jeffrey Vest, Brian L Wiens, Pamela Vig, Star Seyedkazemi, Zachary Goodman, Vincent Wai-Sun Wong, Rohit Loomba, Frank Tacke, Arun Sanyal, Eric Lefebvre
Articles, Abstracts, and Reports
The aim of this study was to evaluate cenicriviroc (CVC), a dual antagonist of CC chemokine receptor types 2 and 5, for treatment of nonalcoholic steatohepatitis (NASH) with liver fibrosis (LF). A randomized, double-blind, multinational phase 2b study enrolled subjects with NASH, a nonalcoholic fatty liver disease activity score (NAS) ≥4, and LF (stages 1-3, NASH Clinical Research Network) at 81 clinical sites. Subjects (N = 289) were randomly assigned CVC 150 mg or placebo. Primary outcome was ≥2-point improvement in NAS and no worsening of fibrosis at year 1. Key secondary outcomes were: resolution of steatohepatitis (SH) and no …
A Randomized Trial Of Obeticholic Acid Monotherapy In Patients With Primary Biliary Cholangitis., Kris V Kowdley, Velimir Luketic, Roger Chapman, Gideon M Hirschfield, Raoul Poupon, Christoph Schramm, Catherine Vincent, Christian Rust, Albert Parés, Andrew Mason, Hanns-Ulrich Marschall, David Shapiro, Luciano Adorini, Cathi Sciacca, Tessa Beecher-Jones, Olaf Böhm, Richard Pencek, David Jones
A Randomized Trial Of Obeticholic Acid Monotherapy In Patients With Primary Biliary Cholangitis., Kris V Kowdley, Velimir Luketic, Roger Chapman, Gideon M Hirschfield, Raoul Poupon, Christoph Schramm, Catherine Vincent, Christian Rust, Albert Parés, Andrew Mason, Hanns-Ulrich Marschall, David Shapiro, Luciano Adorini, Cathi Sciacca, Tessa Beecher-Jones, Olaf Böhm, Richard Pencek, David Jones
Articles, Abstracts, and Reports
Obeticholic acid (OCA), a potent farnesoid X receptor agonist, was studied as monotherapy in an international, randomized, double-blind, placebo-controlled phase 2 study in patients with primary biliary cholangitis who were then followed for up to 6 years. The goals of the study were to assess the benefit of OCA in the absence of ursodeoxycholic acid, which is relevant for patients who are intolerant of ursodeoxycholic acid and at higher risk of disease progression. Patients were randomized and dosed with placebo (n = 23), OCA 10 mg (n = 20), or OCA 50 mg (n = 16) given as monotherapy once …
Recognizing Our Experts:, Karsten Wiechert, Jens R Chapman, Jeffrey C Wang
Recognizing Our Experts:, Karsten Wiechert, Jens R Chapman, Jeffrey C Wang
Articles, Abstracts, and Reports
No abstract provided.
Digitizing Omics Profiles By Divergence From A Baseline., Wikum Dinalankara, Qian Ke, Yiran Xu, Lanlan Ji, Nicole Pagane, Anching Lien, Tejasvi Matam, Elana J Fertig, Nathan D Price, Laurent Younes, Luigi Marchionni, Donald Geman
Digitizing Omics Profiles By Divergence From A Baseline., Wikum Dinalankara, Qian Ke, Yiran Xu, Lanlan Ji, Nicole Pagane, Anching Lien, Tejasvi Matam, Elana J Fertig, Nathan D Price, Laurent Younes, Luigi Marchionni, Donald Geman
Articles, Abstracts, and Reports
Data collected from omics technologies have revealed pervasive heterogeneity and stochasticity of molecular states within and between phenotypes. A prominent example of such heterogeneity occurs between genome-wide mRNA, microRNA, and methylation profiles from one individual tumor to another, even within a cancer subtype. However, current methods in bioinformatics, such as detecting differentially expressed genes or CpG sites, are population-based and therefore do not effectively model intersample diversity. Here we introduce a unified theory to quantify sample-level heterogeneity that is applicable to a single omics profile. Specifically, we simplify an omics profile to a digital representation based on the omics profiles …
Potent Immune Modulation By Medi6383, An Engineered Human Ox40 Ligand Igg4p Fc Fusion Protein., Michael D Oberst, Catherine Augé, Chad Morris, Stacy Kentner, Kathy Mulgrew, Kelly Mcglinchey, James Hair, Shino Hanabuchi, Qun Du, Melissa Damschroder, Hui Feng, Steven Eck, Nicholas Buss, Lolke De Haan, Andrew J Pierce, Haesun Park, Andrew Sylwester, Michael K Axthelm, Louis Picker, Nicholas P Morris, Andrew D Weinberg, Scott A Hammond
Potent Immune Modulation By Medi6383, An Engineered Human Ox40 Ligand Igg4p Fc Fusion Protein., Michael D Oberst, Catherine Augé, Chad Morris, Stacy Kentner, Kathy Mulgrew, Kelly Mcglinchey, James Hair, Shino Hanabuchi, Qun Du, Melissa Damschroder, Hui Feng, Steven Eck, Nicholas Buss, Lolke De Haan, Andrew J Pierce, Haesun Park, Andrew Sylwester, Michael K Axthelm, Louis Picker, Nicholas P Morris, Andrew D Weinberg, Scott A Hammond
Articles, Abstracts, and Reports
Ligation of OX40 (CD134, TNFRSF4) on activated T cells by its natural ligand (OX40L, CD252, TNFSF4) enhances cellular survival, proliferation, and effector functions such as cytokine release and cellular cytotoxicity. We engineered a recombinant human OX40L IgG4P Fc fusion protein termed MEDI6383 that assembles into a hexameric structure and exerts potent agonist activity following engagement of OX40. MEDI6383 displayed solution-phase agonist activity that was enhanced when the fusion protein was clustered by Fc gamma receptors (FcγRs) on the surface of adjacent cells. The resulting costimulation of OX40 on T cells induced NFκB promoter activity in OX40-expressing T cells and induced …
Improved Cognitive Outcomes In Patients With Relapsing-Remitting Multiple Sclerosis Treated With Daclizumab Beta: Results From The Decide Study., Ralph Hb Benedict, Stanley Cohan, Sharon G Lynch, Katherine Riester, Ping Wang, Wanda Castro-Borrero, Jacob Elkins, Guido Sabatella
Improved Cognitive Outcomes In Patients With Relapsing-Remitting Multiple Sclerosis Treated With Daclizumab Beta: Results From The Decide Study., Ralph Hb Benedict, Stanley Cohan, Sharon G Lynch, Katherine Riester, Ping Wang, Wanda Castro-Borrero, Jacob Elkins, Guido Sabatella
Articles, Abstracts, and Reports
BACKGROUND: Cognitive impairment is common in multiple sclerosis (MS), with cognitive processing speed being the most frequently affected domain.
OBJECTIVE: Examine the effects of daclizumab beta versus intramuscular (IM) interferon (IFN) beta-1a on cognitive processing speed as assessed by Symbol Digit Modalities Test (SDMT).
METHODS: In DECIDE, patients with relapsing-remitting multiple sclerosis (RRMS) (age: 18-55 years; Expanded Disability Status Scale (EDSS) score 0-5.0) were randomized to daclizumab beta ( n = 919) or IM IFN beta-1a ( n = 922) for 96-144 weeks. SDMT was administered at baseline and at 24-week intervals.
RESULTS: At week 96, significantly greater mean improvement …
Loss Of Inter-Cellular Cooperation By Complete Epithelial-Mesenchymal Transition Supports Favorable Outcomes In Basal Breast Cancer Patients., Anne Grosse-Wilde, Rolf E Kuestner, Stephanie M Skelton, Ellie Macintosh, Aymeric Fouquier D'Hérouël, Gökhan Ertaylan, Antonio Del Sol, Alexander Skupin, Sui Huang
Loss Of Inter-Cellular Cooperation By Complete Epithelial-Mesenchymal Transition Supports Favorable Outcomes In Basal Breast Cancer Patients., Anne Grosse-Wilde, Rolf E Kuestner, Stephanie M Skelton, Ellie Macintosh, Aymeric Fouquier D'Hérouël, Gökhan Ertaylan, Antonio Del Sol, Alexander Skupin, Sui Huang
Articles, Abstracts, and Reports
According to the sequential metastasis model, aggressive mesenchymal (M) metastasis-initiating cells (MICs) are generated by an epithelial-mesenchymal transition (EMT) which eventually is reversed by a mesenchymal-epithelial transition (MET) and outgrowth of life-threatening epithelial (E) macrometastases. Paradoxically, in breast cancer M signatures are linked with more favorable outcomes than E signatures, and M cells are often dispensable for metastasis in mouse models. Here we present evidence at the cellular and patient level for the cooperation metastasis model, according to which E cells are MICs, while M cells merely support E cell persistence through cooperation. We tracked the fates of co-cultured E …
Macrophage-Derived Il-1Β/Nf-Κb Signaling Mediates Parenteral Nutrition-Associated Cholestasis., Karim C El Kasmi, Padade M Vue, Aimee L Anderson, Michael W Devereaux, Swati Ghosh, Natarajan Balasubramaniyan, Sophie A Fillon, Carola Dahrenmoeller, Ayed Allawzi, Crystal Woods, Sarah Mckenna, Clyde J Wright, Linda Johnson, Angelo D'Alessandro, Julie A Reisz, Eva Nozik-Grayck, Frederick J Suchy, Ronald J Sokol
Macrophage-Derived Il-1Β/Nf-Κb Signaling Mediates Parenteral Nutrition-Associated Cholestasis., Karim C El Kasmi, Padade M Vue, Aimee L Anderson, Michael W Devereaux, Swati Ghosh, Natarajan Balasubramaniyan, Sophie A Fillon, Carola Dahrenmoeller, Ayed Allawzi, Crystal Woods, Sarah Mckenna, Clyde J Wright, Linda Johnson, Angelo D'Alessandro, Julie A Reisz, Eva Nozik-Grayck, Frederick J Suchy, Ronald J Sokol
Articles, Abstracts, and Reports
In infants intolerant of enteral feeding because of intestinal disease, parenteral nutrition may be associated with cholestasis, which can progress to end-stage liver disease. Here we show the function of hepatic macrophages and phytosterols in parenteral nutrition-associated cholestasis (PNAC) pathogenesis using a mouse model that recapitulates the human pathophysiology and combines intestinal injury with parenteral nutrition. We combine genetic, molecular, and pharmacological approaches to identify an essential function of hepatic macrophages and IL-1β in PNAC. Pharmacological antagonism of IL-1 signaling or genetic deficiency in CCR2, caspase-1 and caspase-11, or IL-1 receptor (which binds both IL-1α and IL-1β) prevents PNAC in …
Coordinated Responses To Individual Tumor Antigens By Igg Antibody And Cd8+ T Cells Following Cancer Vaccination., Tyler W Hulett, Shawn M. Jensen, Phillip A Wilmarth, Ashok P Reddy, Carmen Ballesteros-Merino, Michael E Afentoulis, Christopher Dubay, Larry L David, Bernard A Fox
Coordinated Responses To Individual Tumor Antigens By Igg Antibody And Cd8+ T Cells Following Cancer Vaccination., Tyler W Hulett, Shawn M. Jensen, Phillip A Wilmarth, Ashok P Reddy, Carmen Ballesteros-Merino, Michael E Afentoulis, Christopher Dubay, Larry L David, Bernard A Fox
Articles, Abstracts, and Reports
BACKGROUND: One of today's greatest hurdles for cancer immunotherapy is the absence of information regarding which tumor antigens are already recognized by patients receiving immunotherapies, and whether those therapies then boost or generate an immune response against tumor proteins. For CD8+ T cells in particular, patient-specific immune recognition and responses at the level of individual tumor antigens are rarely characterized. Because of this, some immunologists have turned to serum antibodies as an alternative measure of antigen-specific anti-tumor immunity. In this work, we sought to simultaneously interrogate serum IgG and CD8+ T cell recognition of individual tumor antigens to determine whether …
Driver Fusions And Their Implications In The Development And Treatment Of Human Cancers., Qingsong Gao, Wen-Wei Liang, Steven M Foltz, Gnanavel Mutharasu, Reyka G Jayasinghe, Song Cao, Wen-Wei Liao, Sheila M Reynolds, Matthew A Wyczalkowski, Lijun Yao, Lihua Yu, Sam Q Sun, Ken Chen, Alexander J Lazar, Ryan C Fields, Michael C Wendl, Brian A Van Tine, Ravi Vij, Feng Chen, Matti Nykter, Ilya Shmulevich, Li Ding
Driver Fusions And Their Implications In The Development And Treatment Of Human Cancers., Qingsong Gao, Wen-Wei Liang, Steven M Foltz, Gnanavel Mutharasu, Reyka G Jayasinghe, Song Cao, Wen-Wei Liao, Sheila M Reynolds, Matthew A Wyczalkowski, Lijun Yao, Lihua Yu, Sam Q Sun, Ken Chen, Alexander J Lazar, Ryan C Fields, Michael C Wendl, Brian A Van Tine, Ravi Vij, Feng Chen, Matti Nykter, Ilya Shmulevich, Li Ding
Articles, Abstracts, and Reports
Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of …
Genomic And Molecular Landscape Of Dna Damage Repair Deficiency Across The Cancer Genome Atlas., Theo A Knijnenburg, Linghua Wang, Michael T Zimmermann, Nyasha Chambwe, Galen F Gao, Andrew D Cherniack, Huihui Fan, Hui Shen, Gregory P Way, Casey S Greene, Yuexin Liu, Rehan Akbani, Bin Feng, Lawrence A Donehower, Chase Miller, Yang Shen, Mostafa Karimi, Haoran Chen, Pora Kim, Peilin Jia, Eve Shinbrot, Shaojun Zhang, Jianfang Liu, Hai Hu, Matthew H Bailey, Christina Yau, Denise Wolf, Zhongming Zhao, John N Weinstein, Lei Li, Li Ding, Gordon B Mills, Peter W Laird, David A Wheeler, Ilya Shmulevich, Raymond J Monnat, Yonghong Xiao, Chen Wang
Genomic And Molecular Landscape Of Dna Damage Repair Deficiency Across The Cancer Genome Atlas., Theo A Knijnenburg, Linghua Wang, Michael T Zimmermann, Nyasha Chambwe, Galen F Gao, Andrew D Cherniack, Huihui Fan, Hui Shen, Gregory P Way, Casey S Greene, Yuexin Liu, Rehan Akbani, Bin Feng, Lawrence A Donehower, Chase Miller, Yang Shen, Mostafa Karimi, Haoran Chen, Pora Kim, Peilin Jia, Eve Shinbrot, Shaojun Zhang, Jianfang Liu, Hai Hu, Matthew H Bailey, Christina Yau, Denise Wolf, Zhongming Zhao, John N Weinstein, Lei Li, Li Ding, Gordon B Mills, Peter W Laird, David A Wheeler, Ilya Shmulevich, Raymond J Monnat, Yonghong Xiao, Chen Wang
Articles, Abstracts, and Reports
DNA damage repair (DDR) pathways modulate cancer risk, progression, and therapeutic response. We systematically analyzed somatic alterations to provide a comprehensive view of DDR deficiency across 33 cancer types. Mutations with accompanying loss of heterozygosity were observed in over 1/3 of DDR genes, including TP53 and BRCA1/2. Other prevalent alterations included epigenetic silencing of the direct repair genes EXO5, MGMT, and ALKBH3 in ∼20% of samples. Homologous recombination deficiency (HRD) was present at varying frequency in many cancer types, most notably ovarian cancer. However, in contrast to ovarian cancer, HRD was associated with worse outcomes in several other cancers. Protein …
Systematic Analysis Of Splice-Site-Creating Mutations In Cancer., Reyka G Jayasinghe, Song Cao, Qingsong Gao, Michael C Wendl, Nam Sy Vo, Sheila M Reynolds, Yanyan Zhao, Héctor Climente-González, Shengjie Chai, Fang Wang, Rajees Varghese, Mo Huang, Wen-Wei Liang, Matthew A Wyczalkowski, Sohini Sengupta, Zhi Li, Samuel H Payne, David Fenyö, Jeffrey H Miner, Matthew J Walter, Benjamin Vincent, Eduardo Eyras, Ken Chen, Ilya Shmulevich, Feng Chen, Li Ding
Systematic Analysis Of Splice-Site-Creating Mutations In Cancer., Reyka G Jayasinghe, Song Cao, Qingsong Gao, Michael C Wendl, Nam Sy Vo, Sheila M Reynolds, Yanyan Zhao, Héctor Climente-González, Shengjie Chai, Fang Wang, Rajees Varghese, Mo Huang, Wen-Wei Liang, Matthew A Wyczalkowski, Sohini Sengupta, Zhi Li, Samuel H Payne, David Fenyö, Jeffrey H Miner, Matthew J Walter, Benjamin Vincent, Eduardo Eyras, Ken Chen, Ilya Shmulevich, Feng Chen, Li Ding
Articles, Abstracts, and Reports
For the past decade, cancer genomic studies have focused on mutations leading to splice-site disruption, overlooking those having splice-creating potential. Here, we applied a bioinformatic tool, MiSplice, for the large-scale discovery of splice-site-creating mutations (SCMs) across 8,656 TCGA tumors. We report 1,964 originally mis-annotated mutations having clear evidence of creating alternative splice junctions. TP53 and GATA3 have 26 and 18 SCMs, respectively, and ATRX has 5 from lower-grade gliomas. Mutations in 11 genes, including PARP1, BRCA1, and BAP1, were experimentally validated for splice-site-creating function. Notably, we found that neoantigens induced by SCMs are likely several folds more immunogenic compared to …
Spatial Organization And Molecular Correlation Of Tumor-Infiltrating Lymphocytes Using Deep Learning On Pathology Images., Joel Saltz, Rajarsi Gupta, Le Hou, Tahsin Kurc, Pankaj Singh, Vu Nguyen, Dimitris Samaras, Kenneth R Shroyer, Tianhao Zhao, Rebecca Batiste, John Van Arnam, Ilya Shmulevich, Arvind U K Rao, Alexander J Lazar, Ashish Sharma, Vésteinn Thorsson
Spatial Organization And Molecular Correlation Of Tumor-Infiltrating Lymphocytes Using Deep Learning On Pathology Images., Joel Saltz, Rajarsi Gupta, Le Hou, Tahsin Kurc, Pankaj Singh, Vu Nguyen, Dimitris Samaras, Kenneth R Shroyer, Tianhao Zhao, Rebecca Batiste, John Van Arnam, Ilya Shmulevich, Arvind U K Rao, Alexander J Lazar, Ashish Sharma, Vésteinn Thorsson
Articles, Abstracts, and Reports
Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumor-infiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched …
Clinical Outcomes Of Endovascular Thrombectomy In Tissue Plasminogen Activator Versus Non-Tissue Plasminogen Activator Patients At Primary Stroke Care Centers., Gregory Imbarrato, Joshua Bentley, Ajeet Gordhan
Clinical Outcomes Of Endovascular Thrombectomy In Tissue Plasminogen Activator Versus Non-Tissue Plasminogen Activator Patients At Primary Stroke Care Centers., Gregory Imbarrato, Joshua Bentley, Ajeet Gordhan
Articles, Abstracts, and Reports
Background: The effect of intravenous tissue plasminogen activator (IV tPA) administration before endovascular intervention as compared to without at thrombectomy-capable low-volume centers on procedural aspects and patient outcomes has not been investigated.
Methods: Retrospective chart review was performed in all consecutive large vessel cerebrovascular accident patients treated with endovascular therapy at two select rural primary stroke centers between 2011 and 2015. Patients' data regarding age, sex, and medical history, as well as thrombus location by catheter-based cerebral angiography, postprocedural reperfusion status, and clinical outcomes were reviewed. The primary outcome measure of the study was a comparison of modified Rankin scale …
Hospital-Based Physicians' Intubation Decisions And Associated Mental Models When Managing A Critically And Terminally Ill Older Patient., Shannon Haliko, Julie Downs, Deepika Mohan, Robert Arnold, Amber E Barnato
Hospital-Based Physicians' Intubation Decisions And Associated Mental Models When Managing A Critically And Terminally Ill Older Patient., Shannon Haliko, Julie Downs, Deepika Mohan, Robert Arnold, Amber E Barnato
Articles, Abstracts, and Reports
BACKGROUND: Variation in the intensity of acute care treatment at the end of life is influenced more strongly by hospital and provider characteristics than patient preferences.
OBJECTIVE: We sought to describe physicians' mental models (i.e., thought processes) when encountering a simulated critically and terminally ill older patient, and to compare those models based on whether their treatment plan was patient preference-concordant or preference-discordant.
METHODS: Seventy-three hospital-based physicians from 3 academic medical centers engaged in a simulated patient encounter and completed a mental model interview while watching the video recording of their encounter. We used an "expert" model to code the …
Response By Zghaib Et Al To Letter Regarding Article, "Standard Ablation Versus Magnetic Resonance Imaging-Guided Ablation In The Treatment Of Ventricular Tachycardia"., Tarek Zghaib, Esra G Ipek, Rozann Hansford, Hiroshi Ashikaga, Ronald D Berger, Joseph E Marine, David D Spragg, Harikrishna Tandri, Stefan L Zimmerman, Henry Halperin, Scott Brancato, Hugh Calkins, Charles Henrikson, Saman Nazarian
Response By Zghaib Et Al To Letter Regarding Article, "Standard Ablation Versus Magnetic Resonance Imaging-Guided Ablation In The Treatment Of Ventricular Tachycardia"., Tarek Zghaib, Esra G Ipek, Rozann Hansford, Hiroshi Ashikaga, Ronald D Berger, Joseph E Marine, David D Spragg, Harikrishna Tandri, Stefan L Zimmerman, Henry Halperin, Scott Brancato, Hugh Calkins, Charles Henrikson, Saman Nazarian
Articles, Abstracts, and Reports
No abstract provided.
Blood Transfusion And Postoperative Infection In Spine Surgery: A Systematic Review., Christian Fisahn, Cameron Schmidt, Josh E Schroeder, Emiliano Vialle, Isador H Lieberman, Joseph R Dettori, Thomas A Schildhauer
Blood Transfusion And Postoperative Infection In Spine Surgery: A Systematic Review., Christian Fisahn, Cameron Schmidt, Josh E Schroeder, Emiliano Vialle, Isador H Lieberman, Joseph R Dettori, Thomas A Schildhauer
Articles, Abstracts, and Reports
Study Design: Systematic review.
Objectives: Allogeneic blood transfusion-related immunomodulation may relatively suppress the immune system, heightening the risk of infection following spine surgery. This systematic review seeks to determine whether allogeneic blood transfusion increases the risk of postoperative infection and whether there are any factors that modify this association.
Methods: PubMed, Cochrane Central Register of Controlled Trials, and reference lists from included studies were searched from inception to April 20, 2017 to identify studies examining the risk of infection following allogeneic blood transfusion in adult patients receiving surgery for degenerative spine disease.
Results: Eleven retrospective cohort or case-control studies, involving …
Upper And Lower Gastrointestinal Endoscopic Findings In Hiv-Infected Patients In The Era Of Highly Active Antiretroviral Therapy., Russell Parvin, Sindhura Kolli, Jamil Shah, Manan Jhaveri, Madhavi Reddy
Upper And Lower Gastrointestinal Endoscopic Findings In Hiv-Infected Patients In The Era Of Highly Active Antiretroviral Therapy., Russell Parvin, Sindhura Kolli, Jamil Shah, Manan Jhaveri, Madhavi Reddy
Articles, Abstracts, and Reports
Background: Endoscopic evaluation with biopsies are instrumental in the diagnosis and management of gastrointestinal (GI) disorders in the setting of human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), especially in the era of highly active antiretroviral therapy (HAART).
Methods: A retrospective chart review of 304 HIV-positive and 199 HIV-negative patients who had undergone upper and/or lower endoscopy in an urban community hospital from the years 2012 - 2017 was performed. Inclusion criteria included men and women between the ages of 45 to 75 years, which had undergone colonoscopies between within 2012 - 2017 and had tested positive for HIV. …
Menopausal-Related Symptoms In Women One Year After Breast Cancer Surgery., Melissa Mazor, Kathryn Lee, Anand Dhruva, Janine K Cataldo, Steven M Paul, Michelle Melisko, Betty J Smoot, Jon D Levine, Charles Elboim, Yvette P Conley, Christine Miaskowksi
Menopausal-Related Symptoms In Women One Year After Breast Cancer Surgery., Melissa Mazor, Kathryn Lee, Anand Dhruva, Janine K Cataldo, Steven M Paul, Michelle Melisko, Betty J Smoot, Jon D Levine, Charles Elboim, Yvette P Conley, Christine Miaskowksi
Articles, Abstracts, and Reports
CONTEXT: Approximately 60% to 100% of women with breast cancer experience at least one menopausal-related symptom. Little is known about associations between menopausal status and symptoms in women 12 months after breast cancer surgery.
OBJECTIVES: The purpose of this study was to evaluate for differences in occurrence, severity, and distress of symptoms between pre- and postmenopausal women 12 months after breast cancer surgery.
METHODS: Women with breast cancer (n = 327) completed the Menopausal Symptoms Scale, which evaluated the occurrence, severity, and distress of 46 common menopausal-related symptoms. Regression analyses were used to evaluate between-group differences in the seven symptoms …
Addressing The Targeting Range Of The Abilhand-56 In Relapsing-Remitting Multiple Sclerosis: A Mixed Methods Psychometric Study., Sophie Cleanthous, Sara Strzok, Farrah Pompilus, Stefan Cano, Patrick Marquis, Stanley Cohan, Myla D Goldman, Kiren Kresa-Reahl, Jennifer Petrillo, Carmen Castrillo-Viguera, Diego Cadavid, Shih-Yin Chen
Addressing The Targeting Range Of The Abilhand-56 In Relapsing-Remitting Multiple Sclerosis: A Mixed Methods Psychometric Study., Sophie Cleanthous, Sara Strzok, Farrah Pompilus, Stefan Cano, Patrick Marquis, Stanley Cohan, Myla D Goldman, Kiren Kresa-Reahl, Jennifer Petrillo, Carmen Castrillo-Viguera, Diego Cadavid, Shih-Yin Chen
Articles, Abstracts, and Reports
Background: ABILHAND, a manual ability patient-reported outcome instrument originally developed for stroke patients, has been used in multiple sclerosis clinical trials; however, psychometric analyses indicated the measure's limited measurement range and precision in higher-functioning multiple sclerosis patients.
Objective: The purpose of this study was to identify candidate items to expand the measurement range of the ABILHAND-56, thus improving its ability to detect differences in manual ability in higher-functioning multiple sclerosis patients.
Methods: A step-wise mixed methods design strategy was used, comprising two waves of patient interviews, a combination of qualitative (concept elicitation and cognitive debriefing) and quantitative (Rasch measurement theory) …