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Acute phase response

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https://www.readbyqxmd.com/read/28645776/selective-inhibition-of-flt3-by-gilteritinib-in-relapsed-or-refractory-acute-myeloid-leukaemia-a-multicentre-first-in-human-open-label-phase-1-2-study
#1
Alexander E Perl, Jessica K Altman, Jorge Cortes, Catherine Smith, Mark Litzow, Maria R Baer, David Claxton, Harry P Erba, Stan Gill, Stuart Goldberg, Joseph G Jurcic, Richard A Larson, Chaofeng Liu, Ellen Ritchie, Gary Schiller, Alexander I Spira, Stephen A Strickland, Raoul Tibes, Celalettin Ustun, Eunice S Wang, Robert Stuart, Christoph Röllig, Andreas Neubauer, Giovanni Martinelli, Erkut Bahceci, Mark Levis
BACKGROUND: Internal tandem duplication mutations in FLT3 are common in acute myeloid leukaemia and are associated with rapid relapse and short overall survival. The clinical benefit of FLT3 inhibitors in patients with acute myeloid leukaemia has been limited by rapid generation of resistance mutations, particularly in codon Asp835 (D835). We aimed to assess the highly selective oral FLT3 inhibitor gilteritinib in patients with relapsed or refractory acute myeloid leukaemia. METHODS: In this phase 1-2 trial, we enrolled patients aged 18 years or older with acute myeloid leukaemia who either were refractory to induction therapy or had relapsed after achieving remission with previous treatment...
June 20, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28645735/serum-amyloid-a-self-assembles-with-phospholipids-to-form-stable-protein-rich-nanoparticles-with-a-distinct-structure-a-hypothetical-function-of-saa-as-a-molecular-mop-in-immune-response
#2
Nicholas M Frame, Shobini Jayaraman, Donald L Gantz, Olga Gursky
Serum amyloid A (SAA) is an acute-phase protein whose action in innate immunity and lipid homeostasis is unclear. Most circulating SAA binds plasma high-density lipoproteins (HDL) and reroutes lipid transport. In vivo SAA binds existing lipoproteins or generates them de novo upon lipid uptake from cells. We explored the products of SAA-lipid interactions and lipoprotein remodeling in vitro. SAA complexes with palmitoyl-oleoyl phosphocholine (POPC) were analyzed for structure and stability using circular dichroism and fluorescence spectroscopy, electron microscopy, gel electrophoresis and gel filtration...
June 20, 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/28645643/management-of-thrombotic-thrombocytopenic-purpura
#3
P Coppo
Daily therapeutic plasma exchange (TPE) transformed the historically fatal prognosis of acquired, anti-ADAMTS13 antibody-mediated thrombotic thrombocytopenic purpura (TTP), leading to the current overall survival rates of >80%. However, relapses occur in up to 40% of patients and refractory disease with fatal outcomes still occurs, typically within the first days of management. In this context, the introduction of rituximab has been the second major breakthrough in TTP management. Rituximab is now routinely recommended during the acute phase, typically in patients with a suboptimal response to treatment, and increasingly as frontline therapy, with high response rates in the following weeks...
June 20, 2017: Transfusion Clinique et Biologique: Journal de la Société Française de Transfusion Sanguine
https://www.readbyqxmd.com/read/28644900/suppression-of-chikungunya-virus-replication-and-differential-innate-responses-of-human-peripheral-blood-mononuclear-cells-during-co-infection-with-dengue-virus
#4
Mariana Ruiz Silva, José A Aguilar Briseño, Vinit Upasani, Heidi van der Ende-Metselaar, Jolanda M Smit, Izabela A Rodenhuis-Zybert
Dengue and chikungunya are viral diseases transmitted to humans by infected Aedes spp. mosquitoes. With an estimated 390 million infected people per year dengue virus (DENV) currently causes the most prevalent arboviral disease. During the last decade chikungunya virus (CHIKV) has caused large outbreaks and has expanded its territory causing millions of cases in Asia, Africa and America. The viruses share a common mosquito vector and during the acute phase cause similar flu-like symptoms that can proceed to more severe or debilitating symptoms...
June 23, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28644774/cd33-splicing-polymorphism-determines-gemtuzumab-ozogamicin-response-in-de-novo-acute-myeloid-leukemia-report-from-randomized-phase-iii-children-s-oncology-group-trial-aaml0531
#5
Jatinder K Lamba, Lata Chauhan, Miyoung Shin, Michael R Loken, Jessica A Pollard, Yi-Cheng Wang, Rhonda E Ries, Richard Aplenc, Betsy A Hirsch, Susana C Raimondi, Roland B Walter, Irwin D Bernstein, Alan S Gamis, Todd A Alonzo, Soheil Meshinchi
Purpose Gemtuzumab ozogamicin (GO), a CD33-targeted immunoconjugate, is a re-emerging therapy for acute myeloid leukemia (AML). CD33 single nucleotide polymorphism rs12459419 C>T in the splice enhancer region regulates the expression of an alternatively spliced CD33 isoform lacking exon2 (D2-CD33), thus eliminating the CD33 IgV domain, which is the antibody-binding site for GO, as well as diagnostic immunophenotypic panels. We aimed to determine the impact of the genotype of this splicing polymorphism in patients with AML treated with GO-containing chemotherapy...
June 23, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28640917/human-hantavirus-infection-elicits-pronounced-redistribution-of-mononuclear-phagocytes-in-peripheral-blood-and-airways
#6
Saskia Scholz, Faezzah Baharom, Gregory Rankin, Kimia T Maleki, Shawon Gupta, Sindhu Vangeti, Jamshid Pourazar, Andrea Discacciati, Jonas Höijer, Matteo Bottai, Niklas K Björkström, Johan Rasmuson, Magnus Evander, Anders Blomberg, Hans-Gustaf Ljunggren, Jonas Klingström, Clas Ahlm, Anna Smed-Sörensen
Hantaviruses infect humans via inhalation of virus-contaminated rodent excreta. Infection can cause severe disease with up to 40% mortality depending on the viral strain. The virus primarily targets the vascular endothelium without direct cytopathic effects. Instead, exaggerated immune responses may inadvertently contribute to disease development. Mononuclear phagocytes (MNPs), including monocytes and dendritic cells (DCs), orchestrate the adaptive immune responses. Since hantaviruses are transmitted via inhalation, studying immunological events in the airways is of importance to understand the processes leading to immunopathogenesis...
June 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28638684/the-new-acr-eular-criteria-for-rheumatoid-arthritis-can-identify-patients-with-same-disease-activity-but-less-damage-by-ultrasound
#7
Sibel Zehra Aydın, Concepcion Castillo-Gallego, Jackie Nam, Jane Freeston, Sarah Horton, Richard J Wakefield, Paul Emery
OBJECTIVE: We aimed to compare the ultrasound findings of patients fulfilling the 1987 ACR [OLD-rheumatoid arthritis (RA)] and the new ACR/EULAR (NEW-RA) classification criteria to examine the impact of the new criteria on disease characteristics, particularly disease duration. MATERIAL AND METHODS: A total of 2730 hands, wrists, elbows, knees, ankles, and foot joints of 105 consecutive patients with inflammatory arthritis, i.e., 82 patients fulfilling the RA criteria (60 patients, OLD-RA; 22 patients, NEW-RA alone) and 23 patients with undifferentiated arthritis, were scanned using ultrasound...
June 2017: European Journal of Rheumatology
https://www.readbyqxmd.com/read/28637582/principles-of-capacity-management-applied-in-the-mental-health-context
#8
Kathryn Zeitz, Darryl Watson
Objective The aim of the paper was to describe a suite of capacity management principles that have been applied in the mental health setting that resulted in a significant reduction in time spent in two emergency departments (ED) and improved throughput.Methods The project consisted of a multifocal change approach over three phases that included: (1) the implementation of a suite of fundamental capacity management activities led by the service and clinical director; (2) a targeted Winter Demand Plan supported by McKinsey and Co...
June 22, 2017: Australian Health Review: a Publication of the Australian Hospital Association
https://www.readbyqxmd.com/read/28637576/antimicrobial-use-and-resistance-in-australia-aura-surveillance-system-coordinating-national-data-on-antimicrobial-use-and-resistance-for-australia
#9
John D Turnidge, Kathy T Meleady
Objective The aim of the present study was to describe the process of establishment and coordination of the national Antimicrobial Use and Resistance in Australia (AURA) surveillance system.Methods Existing surveillance programs conducted by health organisations at state or multi-jurisdictional levels were reviewed, and gaps and opportunities identified for the development of a national system. In view of the time frame available as part of the Australian Government Department of Health funding agreement, the strategy used by the Australian Commission on Safety and Quality in Health Care was to commence work with existing surveillance programs, expanding and enhancing them and developing new systems where gaps were identified...
June 22, 2017: Australian Health Review: a Publication of the Australian Hospital Association
https://www.readbyqxmd.com/read/28633555/glutamine-administration-in-early-or-late-septic-phase-downregulates-lymphocyte-pd-1-pd-l1-expression-and-the-inflammatory-response-in-mice-with-polymicrobial-sepsis
#10
Ya-Mei Hu, Yuan-Chin Hsiung, Man-Hui Pai, Sung-Ling Yeh
BACKGROUND: Sepsis is a severe inflammatory response to infection. Excessive compensation to inflammation leads to dysregulated immune response that ultimately results in organ damage and lethality of sepsis. This study administered glutamine (GLN) in the early or late phase of sepsis to investigate its effects on regulating leukocyte programmed cell death 1 (PD-1) and its ligand (programmed cell death ligand 1 [PD-L1]) expression, macrophage function, inflammation, and acute kidney injury in sepsis...
March 1, 2017: JPEN. Journal of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28633504/a-phase-ii-study-of-palonosetron-aprepitant-dexamethasone-and-olanzapine-for-the-prevention-of-cisplatin-based-chemotherapy-induced-nausea-and-vomiting-in-patients-with-thoracic-malignancy
#11
Kazuhisa Nakashima, Haruyasu Murakami, Kouichi Yokoyama, Shota Omori, Kazushige Wakuda, Akira Ono, Hirotsugu Kenmotsu, Tateaki Naito, Fumie Nishiyama, Mami Kikugawa, Masayo Kaneko, Yumiko Iwamoto, Satomi Koizumi, Keita Mori, Takeshi Isobe, Toshiaki Takahashi
Background: The three-drug combination of a 5-hydroxytryptamine type 3 receptor antagonist, a neurokinin 1 receptor antagonist and dexamethasone is recommended for patients receiving highly emetogenic chemotherapy. However, standard antiemetic therapy is not completely effective in all patients. Methods: We conducted an open-label, single-center, single-arm Phase II study to evaluate the efficacy of olanzapine in combination with standard antiemetic therapy in preventing chemotherapy-induced nausea and vomiting in patients with thoracic malignancy receiving their first cycle of cisplatin-based chemotherapy...
June 17, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28631497/cost-effectiveness-of-blinatumomab-versus-salvage-chemotherapy-in-relapsed-or-refractory-philadelphia-chromosome-negative-b-precursor-acute-lymphoblastic-leukemia-from-a-us-payer-perspective
#12
Thomas E Delea, Jordan Amdahl, Diana Boyko, May Hagiwara, Zachary F Zimmerman, Janet L Franklin, Ze Cong, Guy Hechmati, Anthony Stein
Objective To evaluate the cost-effectiveness of blinatumomab (Blincyto) versus standard of care (SOC) chemotherapy in adults with relapsed or refractory (R/R) Philadelphia-chromosome-negative (Ph-) B-precursor acute lymphoblastic leukemia (ALL) based on the results of the phase 3 TOWER study from a US healthcare payer perspective. Methods The Blincyto Global Economic Model (B-GEM), a partitioned survival model, was used to estimate the incremental cost-effectiveness ratio (ICER) of blinatumomab versus SOC. Response rates, event free survival (EFS), overall survival (OS), numbers of cycles of blinatumomab and SOC, and transplant rates were estimated from TOWER...
June 20, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28630405/sex-differences-in-prostaglandin-biosynthesis-in-neutrophils-during-acute-inflammation
#13
Simona Pace, Antonietta Rossi, Verena Krauth, Friederike Dehm, Fabiana Troisi, Rossella Bilancia, Christina Weinigel, Silke Rummler, Oliver Werz, Lidia Sautebin
The severity and course of inflammatory processes differ between women and men, but the biochemical mechanisms underlying these sex differences are elusive. Prostaglandins (PG) and leukotrienes (LT) are lipid mediators linked to inflammation. We demonstrated superior LT biosynthesis in human neutrophils and monocytes, and in mouse macrophages from females, and we confirmed these sex differences in vivo where female mice produced more LTs during zymosan-induced peritonitis versus males. Here, we report sex differences in PG production in neutrophils during acute inflammation...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630341/pig-model-mimicking-chronic-hepatitis-e-virus-infection-in-immunocompromised-patients-to-assess-immune-correlates-during-chronicity
#14
Dianjun Cao, Qian M Cao, Sakthivel Subramaniam, Danielle M Yugo, C Lynn Heffron, Adam J Rogers, Scott P Kenney, Debin Tian, Shannon R Matzinger, Christopher Overend, Nicholas Catanzaro, Tanya LeRoith, Heng Wang, Pablo Piñeyro, Nicole Lindstrom, Sherrie Clark-Deener, Lijuan Yuan, Xiang-Jin Meng
Chronic hepatitis E virus (HEV) infection is a significant clinical problem in immunocompromised individuals such as organ transplant recipients, although the mechanism remains unknown because of the lack of an animal model. We successfully developed a pig model of chronic HEV infection and examined immune correlates leading to chronicity. The conditions of immunocompromised patients were mimicked by treating pigs with an immunosuppressive regimen including cyclosporine, azathioprine, and prednisolone. Immunocompromised pigs infected with HEV progressed to chronicity, because 8/10 drug-treated HEV-infected pigs continued fecal virus shedding beyond the acute phase of infection, whereas the majority (7/10) of mock-treated HEV-infected pigs cleared fecal viral shedding at 8 wk postinfection...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28630189/in-vitro-activity-of-delafloxacin-and-microbiological-response-against-fluoroquinolone-susceptible-and-non-susceptible-s-aureus-isolates-from-two-phase-3-studies-of-acute-bacterial-skin-and-skin-structure-infections-absssi
#15
S McCurdy, L Lawrence, M Quintas, L Woosley, R Flamm, C Tseng, S Cammarata
Delafloxacin is an investigational anionic fluoroquinolone antibiotic with broad spectrum in vitro activity, including Gram-positive organisms, Gram-negative organisms, atypical organisms, and anaerobes. The in vitro activity of delafloxacin and percent microbiological response in subjects infected with fluoroquinolone susceptible and non-susceptible S. aureus isolates was determined from two global Phase 3 studies of delafloxacin versus vancomycin plus aztreonam in ABSSSI. Patients were enrolled in 23 countries predominately in the US but also Eastern Europe, South America and Asia...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28629782/tnf-phase-iii-signalling-in-tolerant-cells-is-tightly-controlled-by-a20-and-cyld
#16
Rolf Bikker, Martin Christmann, Katharina Preuß, Bastian Welz, Judith Friesenhagen, Oliver Dittrich-Breiholz, René Huber, Korbinian Brand
Following the acute phase of an inflammatory reaction, a strictly controlled resolution of inflammation is necessary. A dysregulation of this process leads to hyperinflammation, chronic inflammatory disease, or immune paralysis. Different mechanisms participate in the coordinated termination of the inflammatory process, e.g. the expression of antiinflammatory molecules and different forms of tolerance. To better understand the processes which mediate resolution of TNF-dependent inflammation and induce tolerance, it is necessary to characterize the signal transduction quality during TNF long-term (pre)incubation...
June 16, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28628884/proteomics-profiling-reveals-inflammatory-biomarkers-of-antidepressant-treatment-response-findings-from-the-co-med-trial
#17
Bharathi S Gadad, Manish K Jha, Bruce D Grannemann, Taryn L Mayes, Madhukar H Trivedi
Animal and human studies suggest an association between depression and aberrant immune response. Further, common inflammatory markers may change during the course of antidepressant treatment in patients. The objective of this study was to evaluate changes in inflammatory markers and clinical outcomes from subjects enrolled in the Combining Medications to Enhance Depression Outcome (CO-MED) trial. At baseline and week 12 (treatment completion), plasma samples of 102 participants were analyzed via a multiplex assay comprised of inflammatory markers using a 27-plex standard assay panel plus a 4-plex human acute phase xMAP technology based platform...
May 26, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28628613/immunosuppressive-and-angiogenic-cytokine-profile-associated-with-bartonella-bacilliformis-infection-in-post-outbreak-and-endemic-areas-of-carrion-s-disease-in-peru
#18
Maria J Pons, Cláudia Gomes, Ruth Aguilar, Diana Barrios, Miguel Angel Aguilar-Luis, Joaquim Ruiz, Carlota Dobaño, Juana Del Valle-Mendoza, Gemma Moncunill
Analysis of immune responses in Bartonella bacilliformis carriers are needed to understand acquisition of immunity to Carrion's disease and may allow identifying biomarkers associated with bacterial infection and disease phases. Serum samples from 144 healthy subjects from 5 villages in the North of Peru collected in 2014 were analyzed. Four villages had a Carrion's disease outbreak in 2013, and the other is a traditionally endemic area. Thirty cytokines, chemokines and growth factors were determined in sera by fluorescent bead-based quantitative suspension array technology, and analyzed in relation to available data on bacteremia quantified by RT-PCR, and IgM and IgG levels measured by ELISA against B...
June 19, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28627459/peripheral-blood-gene-expression-of-acute-phase-proteins-in-people-with-first-episode-psychosis
#19
Jie Yin Yee, Milawaty Nurjono, Wai Yee Ng, Stephanie Ruth Teo, Tih-Shih Lee, Jimmy Lee
BACKGROUND: There is a growing interest in the association between schizophrenia and the activation of inflammatory system with signs of acute phase (AP) response. Majority of such studies had focused on C-reactive protein (CRP). The aims of the present study were (i) to examine the gene expression profiles of other acute phase proteins (APP), namely haptoglobin (HP), alpha-1 antitrypsin (A1T), and alpha-2 macroglobulin (A2M) in patients with first episode psychosis (FEP) over a period of three months and (ii) to explore the association between APP levels and severity of symptoms...
June 13, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28627298/a-prospective-transcranial-doppler-ultrasound-based-evaluation-of-the-acute-and-cumulative-effects-of-sport-related-concussion-on-neurovascular-coupling-response-dynamics
#20
Alexander D Wright, Jonathan D Smirl, Kelsey Bryk, Paul van Donkelaar
Sport-related concussion has been shown to alter cerebral blood flow (CBF) both acutely and chronically, and may exert cumulative effects across multiple injuries. Such dysfunction may be mediated by trauma-induced deficits to CBF control mechanisms, though our understanding of these effects is limited, including dynamics of neurovascular coupling (NVC) responses (i.e. CBF responses to neurologic demand). 179 junior-level contact sport athletes completed preseason testing - 42 reported never having experienced a concussion (Hx-) while 31 had endured three or more (Hx3+)...
June 18, 2017: Journal of Neurotrauma
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