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https://www.readbyqxmd.com/read/27914981/complement-a-primer-for-the-coming-therapeutic-revolution
#1
REVIEW
Scott R Barnum
The complement system is an important part of the innate and adaptive immune systems. Originally characterized as a single serum component contributing to the killing of bacteria, we now know that there are close to sixty complement proteins, multiple activation pathways and a wide range of effector functions mediated by complement. The system plays a critical role in host defense against bacteria, viruses, fungi and other pathogens. However, inappropriate complement activation contributes to the pathophysiology of autoimmune diseases and many inflammatory syndromes...
November 30, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27914561/standards-for-clinical-trials-in-male-and-female-sexual-dysfunction-i-%C3%A2-phase-i-to-phase-iv-clinical-trial-design
#2
William A Fisher, Ilan Gruenwald, Emmanuele A Jannini, Ahinoam Lev-Sagie, Lior Lowenstein, Robert E Pyke, Yakov Reisman, Dennis A Revicki, Eusebio Rubio-Aurioles
This series of articles outlines standards for clinical trials of treatments for male and female sexual dysfunctions, with a focus on research design and patient-reported outcome assessment. These articles consist of revision, updating, and integration of articles on standards for clinical trials in male and female sexual dysfunction from the 2010 International Consultation on Sexual Medicine developed by the authors as part of the 2015 International Consultation on Sexual Medicine. We are guided in this effort by several principles...
December 2016: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/27914503/rationale-and-design-of-the-transcatheter-aortic-valve-replacement-to-unload-the-left-ventricle-in-patients-with-advanced-heart-failure-tavr-unload-trial
#3
Ernest Spitzer, Nicolas M Van Mieghem, Philippe Pibarot, Rebecca T Hahn, Susheel Kodali, Mathew S Maurer, Tamim M Nazif, Josep Rodés-Cabau, Jean-Michel Paradis, Arie-Pieter Kappetein, Ori Ben-Yehuda, Gerrit-Anne van Es, Faouzi Kallel, William N Anderson, Jan Tijssen, Martin B Leon
BACKGROUND: Coexistence of moderate aortic stenosis (AS) in patients with heart failure (HF) with reduced ejection fraction is not uncommon. Moderate AS increases afterload, whereas pharmacologic reduction of afterload is a pillar of contemporary HF management. HYPOTHESIS: Unloading the left ventricle by reducing the transaortic gradient with transfemoral transcatheter aortic valve replacement (TAVR) may improve clinical outcomes in patients with moderate AS and HF with reduced ejection fraction...
December 2016: American Heart Journal
https://www.readbyqxmd.com/read/27914502/rationale-and-design-of-the-progression-of-atherosclerotic-plaque-determined-by-computed-tomographic-angiography-imaging-paradigm-registry-a-comprehensive-exploration-of-plaque-progression-and-its-impact-on-clinical-outcomes-from-a-multicenter-serial-coronary
#4
Sang-Eun Lee, Hyuk-Jae Chang, Asim Rizvi, Martin Hadamitzky, Yong-Jin Kim, Edoardo Conte, Daniele Andreini, Gianluca Pontone, Valentina Volpato, Matthew J Budoff, Ilan Gottlieb, Byoung Kwon Lee, Eun Ju Chun, Filippo Cademartiri, Erica Maffei, Hugo Marques, Jonathon A Leipsic, Sanghoon Shin, Jung Hyun Choi, Namsik Chung, James K Min
BACKGROUND: The natural history of coronary artery disease (CAD) in patients with low-to-intermediate risk is not well characterized. Although earlier invasive serial studies have documented the progression of atherosclerotic burden, most were focused on high-risk patients only. The PARADIGM registry is a large, prospective, multinational dynamic observational registry of patients undergoing serial coronary computed tomographic angiography (CCTA). The primary aim of PARADIGM is to characterize the natural history of CAD in relation to clinical and laboratory data...
December 2016: American Heart Journal
https://www.readbyqxmd.com/read/27914501/levosimendan-in-patients-with-left-ventricular-systolic-dysfunction-undergoing-cardiac-surgery-on-cardiopulmonary-bypass-rationale-and-study-design-of-the-levosimendan-in-patients-with-left-ventricular-systolic-dysfunction-undergoing-cardiac-surgery-requiring
#5
Rajendra H Mehta, Sean Van Diepen, James Meza, Paula Bokesch, Jeffrey D Leimberger, Sandra Tourt-Uhlig, Merri Swartz, Jodi Parrotta, Rachael Jankowich, Douglas Hay, Robert W Harrison, Stephen Fremes, Shaun G Goodman, John Luber, Wolfgang Toller, Matthias Heringlake, Kevin J Anstrom, Jerrold H Levy, Robert A Harrington, John H Alexander
BACKGROUND: Low cardiac output syndrome is associated with increased mortality and occurs in 3% to 14% of patients undergoing cardiac surgery on cardiopulmonary bypass (CPB). Levosimendan, a novel calcium sensitizer and KATP channel activator with inotropic, vasodilatory, and cardioprotective properties, has shown significant promise in reducing the incidence of low cardiac output syndrome and related adverse outcomes in patients undergoing cardiac surgery on CPB. METHODS: LEVO-CTS is a phase 3 randomized, controlled, multicenter study evaluating the efficacy, safety, and cost-effectiveness of levosimendan in reducing morbidity and mortality in high-risk patients with reduced left ventricular ejection fraction (≤35%) undergoing cardiac surgery on CPB...
December 2016: American Heart Journal
https://www.readbyqxmd.com/read/27914497/acute-management-of-stroke-patients-taking-non-vitamin-k-antagonist-oral-anticoagulants-addressing-real-world-anticoagulant-management-issues-in-stroke-aramis-registry-design-and-rationale
#6
Ying Xian, Adrian F Hernandez, Tina Harding, Gregg C Fonarow, Deepak L Bhatt, Robert E Suter, Yosef Khan, Lee H Schwamm, Eric D Peterson
BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs, dabigatran, rivaroxaban, apixaban, and edoxaban) have been increasingly used as alternatives to warfarin for stroke prophylaxis in patients with atrial fibrillation. Yet there is substantial lack of information on how patients on NOACs are currently treated when they have an acute ischemic stroke and the best strategies for treating intracerebral hemorrhage for those on chronic anticoagulation with warfarin or a NOAC. These are critical unmet needs for real world clinical decision making in these emergent patients...
December 2016: American Heart Journal
https://www.readbyqxmd.com/read/27914492/ticagrelor-with-aspirin-or-alone-in-high-risk-patients-after-coronary-intervention-rationale-and-design-of-the-twilight-study
#7
Usman Baber, George Dangas, David J Cohen, C Michael Gibson, Shamir R Mehta, Dominick J Angiolillo, Stuart J Pocock, Mitchell W Krucoff, Adnan Kastrati, E Magnus Ohman, Philippe Gabriel Steg, Juan Badimon, M Urooj Zafar, Jaya Chandrasekhar, Samantha Sartori, Melissa Aquino, Roxana Mehran
BACKGROUND: Dual antiplatelet therapy (DAPT) is necessary to prevent thrombosis yet increases bleeding after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Antiplatelet monotherapy with a potent P2Y12 receptor antagonist may reduce bleeding while maintaining anti thrombotic efficacy compared with conventional DAPT. METHODS: TWILIGHT is a randomized, double-blind placebo-controlled trial evaluating the comparative efficacy and safety of antiplatelet monotherapy versus DAPT in up to 9000 high-risk patients undergoing PCI with DES...
December 2016: American Heart Journal
https://www.readbyqxmd.com/read/27914489/rationale-and-design-of-the-east-west-late-lumen-loss-study-comparison-of-late-lumen-loss-between-eastern-and-western-drug-eluting-stent-study-cohorts
#8
Robert W Harrison, Vaishnavi Radhakrishnan, Peter S Lam, Dominic J Allocco, Sandeep Brar, Martin Fahy, Rebecca Fisher, Fumiaki Ikeno, Philippe Généreux, Takeshi Kimura, Minglei Liu, Weng Kit Lye, Gary S Mintz, Hirofumi Nagai, Yuka Suzuki, Roseann White, John C Allen, Mitchell W Krucoff
BACKGROUND: The contemporary evaluation of novel drug-eluting stents (DES) includes mechanistic observations that characterize postdeployment stent behavior. Quantification of late lumen loss due to neointimal hyperplasia 8-13 months after stent implantation, via quantitative coronary angiography (QCA), constitutes such an observation and is required by most regulatory authorities. Late lumen loss, as determined by QCA, has been validated as a surrogate for clinical endpoints such as target vessel revascularization...
December 2016: American Heart Journal
https://www.readbyqxmd.com/read/27914488/safety-of-6-month-duration-of-dual-antiplatelet-therapy-after-percutaneous-coronary-intervention-in-patients-with-acute-coronary-syndromes-rationale-and-design-of-the-smart-angioplasty-research-team-safety-of-6-month-duration-of-dual-antiplatelet-therapy-after
#9
Joo Myung Lee, Deok-Kyu Cho, Joo-Yong Hahn, Young Bin Song, Taek Kyu Park, Ju-Hyeon Oh, Jin Bae Lee, Joon-Hyung Doh, Sang-Hyun Kim, Jeong Hoon Yang, Jin-Ho Choi, Seung-Hyuck Choi, Sang Hoon Lee, Hyeon-Cheol Gwon
BACKGROUND AND RATIONALE: Dual antiplatelet therapy (DAPT) is a fundamental treatment that optimizes clinical outcomes after percutaneous coronary intervention, especially in patients with acute coronary syndrome (ACS). Although current international guidelines recommend DAPT for at least 12 months after implantation of a drug-eluting stent in patients with ACS, these recommendations are not based on randomized controlled trials dedicated to ACS population. STUDY DESIGN: The SMART-DATE trial is a prospective, multicenter, randomized, and open-label study to demonstrate the noninferiority of 6-month DAPT compared with 12 months or longer DAPT in patients with ACS undergoing percutaneous coronary intervention...
December 2016: American Heart Journal
https://www.readbyqxmd.com/read/27914356/can-podcasts-for-assessment-guidance-and-feedback-promote-self-efficacy-among-undergraduate-nursing-students-a-qualitative-study
#10
Linda C McSwiggan, Maureen Campbell
BACKGROUND: Improving assessment guidance and feedback for students has become an international priority within higher education. Podcasts have been proposed as a tool for enhancing teaching, learning and assessment. However, a stronger theory-based rationale for using podcasts, particularly as a means of facilitating assessment guidance and feedback, is required. OBJECTIVE: To explore students' experiences of using podcasts for assessment guidance and feedback...
November 27, 2016: Nurse Education Today
https://www.readbyqxmd.com/read/27914235/hyaluronan-as-a-promising-excipient-for-ocular-drug-delivery
#11
REVIEW
Michaela Guter, Miriam Breunig
Hyaluronan (HA) is a naturally occurring polysaccharide and well known for its exceptional properties such as high biocompatibility and biodegradability, along with a low immunogenicity. Besides its use for various biomedical applications it recently came into focus as a favorable excipient for the formulation of various ocular therapeutics. This review article summarizes the ocular distribution of HA and its most heavily investigated binding protein "cluster of differentiation 44" (CD44) which is the rationale for the clinical use of HA, primarily as an additive in ocular applications ranging from eye drops to contact lenses...
November 30, 2016: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/27914091/toward-clinical-use-of-the-igg-specific-enzymes-ides-and-endos-against-antibody-mediated-diseases
#12
Mattias Collin, Lars Björck
The endoglycosidase EndoS and the protease IdeS from the human pathogen Streptococcus pyogenes are immunomodulating enzymes hydrolyzing human IgG. IdeS cleaves IgG in the lower hinge region, while EndoS hydrolyzes the conserved N-linked glycan in the Fc region. Both enzymes are remarkably specific for human IgG that after hydrolysis loses most of its effector functions, such as binding to leukocytes and complement activation, all contributing to bacterial evasion of adaptive immunity. However, taken out of their infectious context, we and others have shown that IdeS and EndoS can alleviate autoimmune disease in a number of animal models of antibody-mediated disorders...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27914038/serotonin-5-ht6-receptor-antagonists-in-alzheimer-s-disease-therapeutic-rationale-and-current-development-status
#13
Hilda Ferrero, Maite Solas, Paul T Francis, Maria J Ramirez
Alzheimer's disease (AD) is the most common cause of dementia in elderly people. Because of the lack of effective treatments for this illness, research focused on identifying compounds that restore cognition and functional impairments in patients with AD is a very active field. Since its discovery in 1993, the serotonin 5-HT6 receptor has received increasing attention, and a growing number of studies supported 5-HT6 receptor antagonism as a target for improving cognitive dysfunction in AD. This article reviews the rationale behind investigations into the targeting of 5-HT6 receptors as a symptomatic treatment for cognitive and/or behavioral symptoms of AD...
December 3, 2016: CNS Drugs
https://www.readbyqxmd.com/read/27913990/sirukumab-a-potential-treatment-for-mood-disorders
#14
REVIEW
Aileen J Zhou, Yena Lee, Giacomo Salvadore, Benjamin Hsu, Trehani M Fonseka, Sidney H Kennedy, Roger S McIntyre
Convergent evidence indicates that abnormalities in the innate immune system may be pertinent to the pathogenesis, phenomenology, and possible treatment of several mental disorders. In keeping with this view, the targeting of interleukin-6 with the human monoclonal antibody sirukumab may represent a possible treatment and disease modification approach, for adults with brain-based disorders (e.g., major depressive disorder). A PubMed/Medline database search was performed using the following search terms: sirukumab; anti-IL-6; IL-6; major depressive disorder; inflammation...
December 2, 2016: Advances in Therapy
https://www.readbyqxmd.com/read/27913861/cxcl12-expression-and-pd-l1-expression-serve-as-prognostic-biomarkers-in-hcc-and-are-induced-by-hypoxia
#15
Alexander Semaan, Dimo Dietrich, Dominik Bergheim, Jörn Dietrich, Jörg C Kalff, Vittorio Branchi, Hanno Matthaei, Glen Kristiansen, Hans-Peter Fischer, Diane Goltz
Anti-PD-1 treatment increases anti-tumour immune responses in animal models of hepatocellular carcinoma (HCC). Sorafenib, the mainstay of treatment of HCC patients, however, leads to tumour hypoxia and thereby abrogates the efficacy of anti-PD-1 treatment. This served as a rationale to implement CXCR4 inhibition as adjunct to sorafenib and anti-PD-1 treatment in murine HCC models. We studied the relationship between tumour hypoxia, PD-L1 and CXCL12 expression in human HCC, aiming to test the rationale for triple therapy combining sorafenib, PD-1 immune checkpoint inhibitors and CXCR4 inhibitors...
December 2, 2016: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/27913455/inherited-thrombophilia-a-double-edged-sword
#16
Saskia Middeldorp
Inherited thrombophilia is a blood coagulation disorder that increases the risk for venous thromboembolism (VTE). During the last decades, the practice of testing has evolved from testing selected populations, leading to high perceived risks, to broad testing for various conditions that included VTE, arterial thrombosis, and pregnancy complications. Because results of such tests usually do not guide treatment decisions, not testing patients with VTE for inherited thrombophilia is on the "Choosing Wisely" list endorsed by multiple specialty societies, including ASH...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27912844/heparanase-from-basic-research-to-therapeutic-applications-in-cancer-and-inflammation
#17
Israel Vlodavsky, Preeti Singh, Ilanit Boyango, Lilach Gutter-Kapon, Michael Elkin, Ralph D Sanderson, Neta Ilan
Heparanase, the sole heparan sulfate degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, angiogenesis and metastasis. Heparanase expression is enhanced in almost all cancers examined including various carcinomas, sarcomas and hematological malignancies. Numerous clinical association studies have consistently demonstrated that upregulation of heparanase expression correlates with increased tumor size, tumor angiogenesis, enhanced metastasis and poor prognosis. In contrast, knockdown of heparanase or treatments of tumor-bearing mice with heparanase-inhibiting compounds, markedly attenuate tumor progression further underscoring the potential of anti-heparanase therapy for multiple types of cancer...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27911979/clinicopathological-features-and-clinical-outcomes-associated-with-tp53-and-braf-n-on-v-600-mutations-in-cutaneous-melanoma-patients
#18
Dae Won Kim, Lauren E Haydu, Aron Y Joon, Roland L Bassett, Alan E Siroy, Michael T Tetzlaff, Mark J Routbort, Rodabe N Amaria, Jennifer A Wargo, Jennifer L McQuade, Jan Kemnade, Patrick Hwu, Scott E Woodman, Jason Roszik, Kevin B Kim, Jeffrey E Gershenwald, Alexander J Lazar, Michael A Davies
BACKGROUND: BRAF(V600) , NRAS, TP53, and BRAF(Non-V600) are among the most common mutations detected in non-acral cutaneous melanoma patients. Although several studies have identified clinical and pathological features associated with BRAF(V600) and NRAS mutations, limited data are available regarding the correlates and significance of TP53 and BRAF(Non-V600) mutations. METHODS: This study analyzed the patient demographics, primary tumor features, and clinical outcomes of a large cohort of non-acral cutaneous melanoma patients who had undergone clinically indicated molecular testing (n = 926)...
December 2, 2016: Cancer
https://www.readbyqxmd.com/read/27911856/splicing-factor-ratio-as-an-index-of-epithelial-mesenchymal-transition-and-tumor-aggressiveness-in-breast-cancer
#19
Pietro Fici, Giulia Gallerani, Anne-Pierre Morel, Laura Mercatali, Toni Ibrahim, Emanuela Scarpi, Dino Amadori, Alain Puisieux, Michel Rigaud, Francesco Fabbri
Epithelial-to-mesenchymal transition (EMT) has been shown to be associated with tumor progression and metastasis. During this process in breast cancer, a crucial role is played by alternative splicing systems. To identify a new early prognostic marker of metastasis, we evaluated EMT-related gene expression in breast cell lines, and in primary tumor tissue from 31 patients with early breast cancer, focusing our attention on EMT-related splicing factors ESRP1, ESRP2 and RBFOX2. Results showed that the expression patterns of these genes were indicative of the onset of EMT in in-vitro models, but not in tissue samples...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911116/finding-the-right-route-for-insulin-delivery-an-overview-of-implantable-pump-therapy
#20
Lia Bally, Hood Thabit, Roman Hovorka
Implantable pump therapy adopting the intraperitoneal route of insulin delivery has been available for the past three decades. The key rationale for implantable pump therapy is the restoration of the portal-peripheral insulin gradient of the normal physiology. Uptake in clinical practice is limited to specialized centers and selected patient populations. Areas covered: Implantable pump therapy is discussed, including technical aspects, rationale for its use, and glycemic and non-glycemic effects. Target populations, summaries of clinical studies and issues related to implantable pump therapy are highlighted...
December 2, 2016: Expert Opinion on Drug Delivery
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