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https://www.readbyqxmd.com/read/28687627/phase-ii-trial-of-sorafenib-in-combination-with-capecitabine-in-patients-with-hepatocellular-carcinoma-inst-08-20
#1
Yehuda Patt, Cristhiam Rojas-Hernandez, Houman Mohammad Fekrazad, Pranshu Bansal, Fa Chyi Lee
LESSONS LEARNED: There continues to be a lack of systemic options for advanced hepatocellular carcinoma (HCC); sorafenib and, very recently, regorafenib are the only approved options. There exists a potential to combine sorafenib with chemotherapeutic agents shown to be active in HCC, such as capecitabine, safely.Good tumor response was observed, with objective improvement in a few patients seldom seen by single agent sorafenib; however, because of the limited number of patients, meaningful conclusions on survival cannot be drawn...
July 7, 2017: Oncologist
https://www.readbyqxmd.com/read/28684614/ubiquinol-effects-on-antiphospholipid-syndrome-prothrombotic-profile-a-randomized-placebo-controlled-trial
#2
Carlos Pérez-Sánchez, María Ángeles Aguirre, Patricia Ruiz-Limón, María Carmen Abalos-Aguilera, Yolanda Jiménez-Gómez, Iván Arias-de la Rosa, Antonio Rodriguez-Ariza, Lucía Fernández-Del Río, José Antonio Gonzalez-Reyes, Pedro Segui, Eduardo Collantes-Estévez, Nuria Barbarroja, Francisco Velasco, Savino Sciascia, Irene Cecchi, María José Cuadrado, José Manuel Villalba, Chary López-Pedrera
OBJECTIVE: Antiphospholipid syndrome (APS) leukocytes exhibit an oxidative perturbation, directly linked to alterations in mitochondrial dynamics and metabolism. This disturbance is related to the patients' prothrombotic status and can be prevented by in vitro treatment with coenzyme Q10. Our aim was to investigate short-term effects of in vivo ubiquinol (reduced coenzyme Q10[Qred]) supplementation on markers related to inflammation and thrombosis in APS through a prospective, randomized, crossover, placebo-controlled trial...
July 6, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28682809/mechanisms-of-erosion-of-atherosclerotic-plaques
#3
Thibaut Quillard, Grégory Franck, Thomas Mawson, Eduardo Folco, Peter Libby
PURPOSE OF REVIEW: The present review explores the mechanisms of superficial intimal erosion, a common cause of thrombotic complications of atherosclerosis. RECENT FINDINGS: Human coronary artery atheroma that give rise to thrombosis because of erosion differ diametrically from those associated with fibrous cap rupture. Eroded lesions characteristically contain few inflammatory cells, abundant extracellular matrix, and neutrophil extracellular traps (NETs). Innate immune mechanisms such as engagement of Toll-like receptor 2 (TLR2) on cultured endothelial cells can impair their viability, attachment, and ability to recover a wound...
July 5, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28678391/interferon-lambda1-il-29-and-inorganic-polyphosphate-are-novel-regulators-of-neutrophil-driven-thromboinflammation
#4
Akrivi Chrysanthopoulou, Konstantinos Kambas, Dimitrios Stakos, Ioannis Mitroulis, Alexandros Mitsios, Veroniki Vidali, Iliana Angelidou, Magdalena Bochenek, Stella Arelaki, Athanasios Arampatzioglou, Ioanna-Evdokia Galani, Panagiotis Skendros, Elias A Couladouros, Stavros Konstantinides, Evangelos Andreakos, Katrin Schäfer, Konstantinos Ritis
Neutrophils and neutrophil-released meshwork structures termed neutrophil extracellular traps (NETs) are major mediators of thromboinflammation and emerging targets for therapy, yet the mechanisms and pathways that control the role of neutrophils in thromboinflammation remain poorly understood. Here, we explored the role of IFN-λ1/IL-29, a major antiviral cytokine recently shown to suppress the neutrophil migratory capacity, in prothrombotic and proNETotic functions of neutrophils. In an ex vivo human experimental setting of acute ST-segment elevation myocardial infarction (STEMI), we show that IFN-λ1/IL-29 hinders NET release and diminishes the amount of cytoplasmic TF in neutrophils...
July 5, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28654465/high-velocity-paint-gun-injuries
#5
Wendi E Wohltmann, Joshua A Wisell, Celina M C Lafrades, Daniel M Cramer, Bruce D Ragsdale
Cutaneous injuries due to industrial high-pressure paint guns are well-documented in the literature; however, the histologic characteristics are uncommonly described, and facial involvement has not been previously reported. Histopathologic features of paint gun injuries vary depending on the time since injection and type of material. Early lesions display an acute neutrophilic infiltrate, edema, and thrombosis, with varying degrees of skin, fat, and muscle necrosis. More developed lesions (120-192 hours after injury) have prominent histiocytes and fibrosis around necrotic foci, possibly with the pitfall of muscle regenerative giant cells that could be mistaken for sarcoma...
June 20, 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28650848/ser-thr-protein-kinase-b2-nadph-oxidase-2-signaling-in-thromboinflammation
#6
Jing Li, Jaehyung Cho
PURPOSE OF REVIEW: Interactions between neutrophils and platelets contribute to the progression of thromboinflammatory disease. However, the regulatory mechanism governing these interactions is poorly understood. The present review focuses on the crucial role of Ser/Thr protein kinase B (AKT)2-NADPH oxidase 2 (NOX2) signaling in regulating neutrophil and platelet activation and their heterotypic interactions under thromboinflammatory conditions. RECENT FINDINGS: Growing evidence has shown that platelets, leukocytes, and blood coagulation need to be considered to treat thromboinflammatory disease in which inflammation and thrombosis occur concurrently...
June 24, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28640782/perioperative-venous-thromboembolism-a-review
#7
Ronald J Gordon, Frederick W Lombard
Venous thromboembolism (VTE) is a significant problem in the perioperative period, increasing patient morbidity, mortality, and health care costs. It is also considered the most preventable of the major postoperative complications. Despite widespread adoption of prophylaxis guidelines, it appears that morbidity from the disease has not substantially changed within the past 2 decades. It is becoming clear that current prophylaxis efforts are not sufficient. Using more potent anticoagulants may decrease the incidence of VTE, but increase the risk for bleeding and infection...
June 20, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28634671/venous-thromboembolism-is-an-independent-predictor-of-mortality-among-patients-with-gastric-cancer
#8
Harry E Fuentes, D M Oramas, L H Paz, Y Wang, X A Andrade, A J Tafur
BACKGROUND: Venous thromboembolism (VTE) is an independent predictor of death among patients with cancer. Patients with gastric cancer (GC) are at higher risk for VTE when compared to other solid tumors, and if one considers its prevalence, GC may be responsible for one of the highest incidences of cancer-associated thrombosis. The impact of VTE on mortality is not well defined among patients with GC. AIM: The aim of this study is to measure the impact of VTE as independent predictor of GC mortality...
June 21, 2017: Journal of Gastrointestinal Cancer
https://www.readbyqxmd.com/read/28611024/platelet-amyloid-precursor-protein-is-a-modulator-of-venous-thromboembolism-in-mice
#9
Ilaria Canobbio, Caterina Visconte, Stefania Momi, Gianni Francesco Guidetti, Marta Zarà, Jessica Canino, Emanuela Falcinelli, Paolo Gresele, Mauro Torti
The amyloid precursor protein (APP), primarily known as the precursor of amyloid peptides that accumulate in the brain of Alzheimer's disease patients, is abundant in platelets but its physiological function remains unknown. In this study, we investigated the role of APP in hemostasis and thrombosis using APP knockout (KO) mice. Ex vivo aggregation, secretion, and integrin αIIbβ3 inside-out activation induced by several agonists were normal in APP-deficient platelets, but the number of circulating platelets was reduced by about 20%, and their size was slightly increased...
June 13, 2017: Blood
https://www.readbyqxmd.com/read/28594748/inhibition-of-spleen-tyrosine-kinase-reduces-renal-allograft-injury-in-a-rat-model-of-acute-antibody-mediated-rejection-in-sensitized-recipients
#10
Sharmila Ramessur Chandran, Yingjie Han, Greg H Tesch, Julie Di Paolo, William R Mulley, John Kanellis, Frank Y Ma, David J Nikolic-Paterson
BACKGROUND: Organ transplantation into sensitized patients with preexisting donor-specific antibodies (DSA) is very challenging. Spleen tyrosine kinase (Syk) promotes leukocyte recruitment and activation via signalling through various cell surface receptors. We investigated whether a selective Syk inhibitor (GS-492429) could suppress antibody-mediated rejection (AMR) in a rat model of AMR in sensitized recipients. METHODS: Recipient Lewis rats (RT1) were immunized with donor (Dark Agouti, RT1) spleen cells (day -5)...
June 7, 2017: Transplantation
https://www.readbyqxmd.com/read/28570273/myeloid-related-protein-14-regulates-deep-vein-thrombosis
#11
Yunmei Wang, Huiyun Gao, Chase W Kessinger, Alvin Schmaier, Farouc A Jaffer, Daniel I Simon
Using transcriptional profiling of platelets from patients presenting with acute myocardial infarction, we identified myeloid-related protein-14 (MRP-14, also known as S100A9) as an acute myocardial infarction gene and reported that platelet MRP-14 binding to platelet CD36 regulates arterial thrombosis. However, whether MRP-14 plays a role in venous thrombosis is unknown. We subjected WT and Mrp-14-deficient (Mrp-14-/-) mice to experimental models of deep vein thrombosis (DVT) by stasis ligation or partial flow restriction (stenosis) of the inferior vena cava...
June 2, 2017: JCI Insight
https://www.readbyqxmd.com/read/28567089/combined-use-of-neutrophil-to-lymphocyte-ratio-and-c-reactive-protein-level-to-predict-clinical-outcomes-in-acute-myocardial-infarction-patients-undergoing-percutaneous-coronary-intervention
#12
Ho-Cheol Shin, Jae-Sik Jang, Han-Young Jin, Jeong-Sook Seo, Tae-Hyun Yang, Dae-Kyeong Kim, Dong-Soo Kim
BACKGROUND AND OBJECTIVES: Both neutrophil to lymphocyte ratio (NLR) and C-reactive protein (CRP) are biomarkers associated with poor prognosis of patients with acute myocardial infarction (AMI). However, the combined usefulness of NLR and CRP in predicting adverse outcomes has not been investigated. SUBJECTS AND METHODS: We analyzed 381 consecutive AMI patients who underwent percutaneous coronary intervention (PCI) from January 2012 to January 2014. The endpoints were all-cause mortality, recurrent myocardial infarction (MI), stent thrombosis, repeat revascularization, stroke, and major adverse cardiac and cerebrovascular events (MACCE) at 2-year follow-up...
May 2017: Korean Circulation Journal
https://www.readbyqxmd.com/read/28538012/antiphospholipid-syndrome-an-update-for-clinicians-and-scientists
#13
Andrew P Vreede, Paula L Bockenstedt, Jason S Knight
PURPOSE OF REVIEW: Antiphospholipid syndrome (APS) is a leading acquired cause of thrombosis and pregnancy loss. Upon diagnosis (which is unlikely to be made until at least one morbid event has occurred), anticoagulant medications are typically prescribed in an attempt to prevent future events. This approach is not uniformly effective and does not prevent associated autoimmune and inflammatory complications. The goal of this review is to update clinicians and scientists on mechanistic and clinically relevant studies from the past 18 months, which have especially focused on inflammatory aspects of APS pathophysiology...
May 22, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28533669/prognostic-value-of-the-neutrophil-to-lymphocyte-ratio-for-hepatocellular-carcinoma-patients-with-portal-hepatic-vein-tumor-thrombosis
#14
Shao-Hua Li, Qiao-Xuan Wang, Zhong-Yuan Yang, Wu Jiang, Cong Li, Peng Sun, Wei Wei, Ming Shi, Rong-Ping Guo
AIM: To investigate whether the preoperative neutrophil-to-lymphocyte ratio (NLR) could predict the prognosis of hepatocellular carcinoma (HCC) patients with portal/hepatic vein tumor thrombosis (PVTT/HVTT) after hepatectomy. METHODS: The study population included 81 HCC patients who underwent hepatectomy and were diagnosed with PVTT/HVTT based on pathological examination. The demographics, laboratory analyses, and histopathology data were analyzed. RESULTS: Overall survival (OS) and disease-free survival (DFS) were determined in the patients with a high (> 2...
May 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28515093/circulating-soluble-p-selectin-must-dimerize-to-promote-inflammation-and-coagulation-in-mice
#15
Sumith R Panicker, Padmaja Mehta-D'souza, Nan Zhang, Arkadiusz G Klopocki, Bojing Shao, Rodger P McEver
Leukocyte adhesion to P-selectin on activated platelets and endothelial cells induces shedding of the P-selectin ectodomain into the circulation. Plasma soluble P-selectin (sP-selectin) is elevated threefold to fourfold in patients with cardiovascular disease. Circulating sP-selectin is thought to trigger signaling in leukocytes that directly contributes to inflammation and thrombosis. However, sP-selectin likely circulates as a monomer, and in vitro studies suggest that sP-selectin must dimerize to induce signaling in leukocytes...
July 13, 2017: Blood
https://www.readbyqxmd.com/read/28504650/neutrophil-derived-s100-calcium-binding-proteins-a8-a9-promote-reticulated-thrombocytosis-and-atherogenesis-in-diabetes
#16
Michael J Kraakman, Man Ks Lee, Annas Al-Sharea, Dragana Dragoljevic, Tessa J Barrett, Emilie Montenont, Debapriya Basu, Sarah Heywood, Helene L Kammoun, Michelle Flynn, Alexandra Whillas, Nordin Mj Hanssen, Mark A Febbraio, Erik Westein, Edward A Fisher, Jaye Chin-Dusting, Mark E Cooper, Jeffrey S Berger, Ira J Goldberg, Prabhakara R Nagareddy, Andrew J Murphy
Platelets play a critical role in atherogenesis and thrombosis-mediated myocardial ischemia, processes that are accelerated in diabetes. Whether hyperglycemia promotes platelet production and whether enhanced platelet production contributes to enhanced atherothrombosis remains unknown. Here we found that in response to hyperglycemia, neutrophil-derived S100 calcium-binding proteins A8/A9 (S100A8/A9) interact with the receptor for advanced glycation end products (RAGE) on hepatic Kupffer cells, resulting in increased production of IL-6, a pleiotropic cytokine that is implicated in inflammatory thrombocytosis...
June 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28465447/human-blood-monocytes-are-able-to-form-extracellular-traps
#17
Vanessa Granger, Dorothée Faille, Vanessa Marani, Benoît Noël, Yann Gallais, Natacha Szely, Héloïse Flament, Marc Pallardy, Sylvie Chollet-Martin, Luc de Chaisemartin
Neutrophil extracellular traps (NETs) are extracellular DNA filaments formed during neutrophil activation. This process, called netosis, was originally associated with neutrophil antibacterial properties. However, several lines of evidence now suggest a major role for netosis in thrombosis, autoimmune diseases, and cancer. We demonstrate here that highly purified human blood monocytes are also capable of extracellular trap (ET) release in response to several stimuli. Monocyte ETs display a morphology analogous to NETs and are associated with myeloperoxidase (MPO), lactoferrin (LF), citrullinated histones, and elastase...
May 2, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28442532/anti-inflammatory-effects-of-simvastatin-during-the-resolution-phase-of-experimentally-formed-venous-thrombi
#18
Yaping Feng, Bo Lei, Fuxian Zhang, Luyuan Niu, Huan Zhang, Mingyi Zhang
Deep venous thrombosis (DVT) is a common vascular disease and is closely linked to inflammation. Over the past decade, the potential antithrombotic effect of statins has been elucidated by clinical studies, primarily through focusing on DVT prevention. The effects of statins on DVT resolution and its underlying mechanisms have been rarely addressed. We established a rabbit model of the inferior vena cava (IVC) venous thrombosis. After 48 hours, the rabbits were treated with saline, heparin, simvastatin, or simvastatin combined with heparin, respectively, for 14 days...
April 25, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28435267/the-acute-pulmonary-and-thrombotic-effects-of-cerium-oxide-nanoparticles-after-intratracheal-instillation-in-mice
#19
Abderrahim Nemmar, Suhail Al-Salam, Sumaya Beegam, Priya Yuvaraju, Badreldin H Ali
Cerium oxide nanoparticles (CeO2 NPs), used as a diesel fuel catalyst, can be emitted into the ambient air, resulting in exposure to humans by inhalation. Recent studies have reported the development of lung toxicity after pulmonary exposure to CeO2 NPs. However, little is known about the possible thrombotic effects of these NPs. The present study investigated the acute (24 hours) effect of intratracheal (IT) instillation of either CeO2 NPs (0.1 or 0.5 mg/kg) or saline (control) on pulmonary and systemic inflammation and oxidative stress and thrombosis in mice...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28428204/flow-perturbation-mediates-neutrophil-recruitment-and-potentiates-endothelial-injury-via-tlr2-in-mice-implications-for-superficial-erosion
#20
Grégory Franck, Thomas Mawson, Grasiele Sausen, Manuel Salinas, Gustavo Santos Masson, Andrew Cole, Marina Beltrami-Moreira, Yiannis Chatzizisis, Thibault Quillard, Yevgenia Tesmenitsky, Eugenia Shvartz, Galina K Sukhova, Filip K Swirski, Matthias Nahrendorf, Elena Aikawa, Kevin J Croce, Peter Libby
RATIONALE: Superficial erosion currently causes up to a third of acute coronary syndromes; yet, we lack understanding of its mechanisms. Thrombi because of superficial intimal erosion characteristically complicate matrix-rich atheromata in regions of flow perturbation. OBJECTIVE: This study tested in vivo the involvement of disturbed flow and of neutrophils, hyaluronan, and Toll-like receptor 2 ligation in superficial intimal injury, a process implicated in superficial erosion...
June 23, 2017: Circulation Research
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