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https://www.readbyqxmd.com/read/27922103/hypothalamic-activation-is-essential-for-endotoxemia-induced-acute-muscle-wasting
#1
Kaipeng Duan, Qiyi Chen, Minhua Cheng, Chenyan Zhao, Zhiliang Lin, Shanjun Tan, Fengchan Xi, Tao Gao, Jialiang Shi, Juanhong Shen, Weiqin Li, Wenkui Yu, Jieshou Li, Ning Li
Growing evidence suggests acute skeletal muscle wasting is a key factor affecting nutritional support and prognosis in critical patients. Previously, plenty of studies of muscle wasting focused on the peripheral pathway, little was known about the central role. We tested the hypothesis whether central inflammatory pathway and neuropeptides were involved in the process. In lipopolysaccharide (LPS) treated rats, hypothalamic NF-κB pathway and inflammation were highly activated, which was accompanied with severe muscle wasting...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27920641/severe-de-novo-hepatitis-b-recovered-from-late-onset-liver-insufficiency-with-prolonged-ascites-and-hypoalbuminemia-due-to-hepatitis-b-virus-genotype-bj-with-precore-mutation
#2
Akira Sato, Toshiya Ishii, Fumiaki Sano, Takayuki Yamada, Hideaki Takahashi, Nobuyuki Matsumoto
De novo hepatitis B is associated with a high risk of hepatic failure often resulting in fatal fulminant hepatitis even when nucleotide analogues are administered. A 77-year-old female developed de novo hepatitis B after R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) treatment for diffuse large B-cell lymphoma. Hepatitis B virus (HBV) isolated from the patient was of genotype Bj, with a precore mutation (G1896A) exhibiting an extremely high viral load at the onset of hepatitis...
September 2016: Case Reports in Gastroenterology
https://www.readbyqxmd.com/read/27920336/reasons-for-discontinuation-and-adverse-effects-of-tnf%C3%AE-inhibitors-in-a-cohort-of-patients-with-rheumatoid-arthritis-and-ankylosing-spondylitis
#3
María Henar García-Lagunar, María Rocío Gutiérrez-Cívicos, María Sergia García-Simón, Pablo Conesa-Zamora, Enrique Jimenez-Santos, Pedro Cano-Vivar, Andrés García-Márquez, Iris Muñoz-García, Alice Charlotte Viney
BACKGROUND: The introduction of anti-tumor necrosis factor α (anti-TNFα) drugs has improved the clinical outcomes in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). However, these drugs may cause adverse effects that motivate a change in or discontinuation of the treatment. OBJECTIVE: To evaluate the causes of discontinuation or changes in the dosage regimen in a cohort of patients with RA and AS treated with infliximab, adalimumab, etanercept, and golimumab under clinical practice conditions...
December 5, 2016: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/27919891/structure-activity-relationships-of-a-series-of-echinocandins-and-the-discovery-of-cd101-a-highly-stable-and-soluble-echinocandin-with-distinctive-pharmacokinetic-properties
#4
Kenneth D James, Christopher P Laudeman, Navdeep B Malkar, Radha Krishnan, Karen Polowy
Echinocandins are first-line therapy for candidemia and invasive candidiasis. They are generally safe with few drug interactions, but the stability and pharmacokinetic properties of currently approved echinocandins are such that each was developed for daily intravenous infusion. We sought to discover a novel echinocandin with properties that would enable more flexible dosing regimens, alternate routes of delivery, and expanded utility. Derivatives of known echinocandin scaffolds were generated, and an iterative process of design and screening led to the discovery of CD101, a novel echinocandin that has since demonstrated improved chemical stability and pharmacokinetics...
December 5, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27919873/managing-transitions-from-oral-factor-xa-inhibitors-to-unfractionated-heparin-infusions
#5
Andrew C Faust, Dave Kanyer, Ann K Wittkowsky
PURPOSE: Published evidence regarding the effects of oral factor Xa inhibitors on anticoagulation monitoring tests is reviewed with a focus on monitoring concerns that can arise during transitions to i.v. heparin therapy. SUMMARY: Assays that measure inhibition of factor Xa activity (i.e., anti-Xa assays) are widely used in U.S. institutions to monitor i.v. heparin therapy and, in some cases, for monitoring other types of anticoagulation therapy. Clinicians have raised concerns that the use of anti-Xa assays to monitor heparin levels in hospitalized patients who must be transitioned from oral factor Xa inhibitor therapy to i...
December 15, 2016: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/27919586/practical-management-of-adverse-events-related-to-apomorphine-therapy
#6
Roongroj Bhidayasiri, Pedro J Garcia Ruiz, Tove Henriksen
The potential for adverse events is often cited as a barrier to the use of subcutaneous apomorphine therapy (intermittent injections and continuous infusion) in the management of Parkinson's disease. However, with proactive management most adverse effects are manageable if reported and tackled early enough. As such, proper clinician and patient awareness of the potential adverse effects is important to minimize their impact on the overall clinical utility of this efficacious antiparkinsonian agent. In this paper, we review the key local and systemic adverse effects reported during apomorphine titration, initiation and long-term treatment, and discuss practical management strategies...
November 27, 2016: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/27918382/conventional-versus-prolonged-infusion-of-meropenem-in-neonates-with-gram-negative-late-onset-sepsis-a-randomized-controlled-trial
#7
Abd Elazeez Shabaan, Islam Nour, Heba Elsayed Eldegla, Nehad Nasef, Basma Shouman, Hesham Abdel-Hady
BACKGROUND: Gram-negative bacteria are associated with significant morbidity and mortality in preterm and term newborns. Meropenem has widespread efficacy and often allows for monotherapy in this group. Prolonged infusion instead of infusion over 30 minutes has been suggested to result in higher microbiologic efficacy. OBJECTIVE: To compare the clinical and microbiologic efficacy and safety of prolonged infusions versus conventional dosing of meropenem in neonates with Gram negative late onset sepsis (GN-LOS)...
November 30, 2016: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/27917453/phase-i-study-of-mrx34-a-liposomal-mir-34a-mimic-administered-twice-weekly-in-patients-with-advanced-solid-tumors
#8
Muhammad S Beg, Andrew J Brenner, Jasgit Sachdev, Mitesh Borad, Yoon-Koo Kang, Jay Stoudemire, Susan Smith, Andreas G Bader, Sinil Kim, David S Hong
Purpose Naturally occurring tumor suppressor microRNA-34a (miR-34a) downregulates the expression of >30 oncogenes across multiple oncogenic pathways, as well as genes involved in tumor immune evasion, but is lost or under-expressed in many malignancies. This first-in-human, phase I study assessed the maximum tolerated dose (MTD), safety, pharmacokinetics, and clinical activity of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumors. Patients and Methods Adult patients with solid tumors refractory to standard treatment were enrolled in a standard 3 + 3 dose escalation trial...
December 5, 2016: Investigational New Drugs
https://www.readbyqxmd.com/read/27916773/a-case-of-unresectable-combined-hepatocellular-cholangiocarcinoma-showing-favorable-response-to-lfp-therapy
#9
Sayuri Kato, Yasuto Takeuchi, Nozomu Wada, Yuuki Morimoto, Kenji Kuwaki, Hideki Ohnishi, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada
A woman in her 50s was admitted to our hospital because of multiple tumors detected in her liver. She was diagnosed with combined hepatocellular cholangiocarcinoma using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and biopsy of the liver tumors. We judged the tumors to be unresectable because they were found in both lobes of the liver, with a tumor thrombus being found in the main left portal vein. The pathological findings showed that the tumors exhibited characteristics of hepatocellular carcinoma...
2016: Nihon Shokakibyo Gakkai Zasshi, the Japanese Journal of Gastro-enterology
https://www.readbyqxmd.com/read/27916638/therapeutical-options-in-the-management-of-carotid-dissection
#10
Ombretta Martinelli, Salvatore Venosi, Jamila BenHamida, Alban Malay, Cristina Belli, Francesco Giosue' Irace, Roberto Gattuso, Giacomo Frati, Bruno Gossetti, Luigi Irace
OBJECTIVE: The best management of carotid artery dissection (CAD) is still controversial ranging from antiplatelet medication to open surgery or endovascular treatment. In this retrospective study we assessed the safety and efficacy of endovascular stent angioplasty for the treatment of CAD. METHODS: From February 2006 to February 2016, 44 patients (28 females and 16 males, age range 25-65 years, mean 42) with CAD were included in this study. The internal carotid artery (ICA) dissection was spontaneous in origin in 32 patients and post-traumatic in the remaining 12 (1 case it was bilateral)...
December 1, 2016: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/27915429/high-risk-pml-patients-switching-from-natalizumab-to-alemtuzumab-an-observational-study
#11
Simona Malucchi, Marco Capobianco, Marianna Lo Re, Maria Malentacchi, Alessia di Sapio, Manuela Matta, Francesca Sperli, Antonio Bertolotto
INTRODUCTION: The choice of therapy in patients withdrawing from natalizumab treatment is still an open question and neurologists need strategies to manage this group of patients. The aim of this study is to evaluate if alemtuzumab is able to control the disease when used in patient who have stopped natalizumab. METHODS: 16 patients stopped natalizumab treatment after a median number of 20 infusions (range 12-114); all the patients were responders to natalizumab (neither clinical nor radiological activity during natalizumab therapy) and the reason for stopping was the risk of PML for all of them...
December 3, 2016: Neurology and Therapy
https://www.readbyqxmd.com/read/27914971/once-weekly-ofatumumab-in-untreated-or-relapsed-waldenstr%C3%A3-m-s-macroglobulinaemia-an-open-label-single-arm-phase-2-study
#12
Richard R Furman, Herbert A Eradat, Christine G DiRienzo, Craig C Hofmeister, Suzanne R Hayman, John P Leonard, Morton Coleman, Ranjana Advani, Asher Chanan-Khan, Julie Switzky, Qiming M Liao, Damini Shah, Roxanne C Jewell, Steen Lisby, Thomas S Lin
BACKGROUND: The development of more effective and safer treatments, especially non-chemotherapeutics, is needed for patients with Waldenström's macroglobulinaemia. The aim of the study was to assess the safety and clinical activity of intravenous ofatumumab monotherapy for untreated and relapsed Waldenström's macroglobulinaemia. METHODS: We did a phase 2, open-label, single-arm study at six centres (hospitals and cancer clinics) in the USA. Patients aged at least 18 years who were diagnosed with untreated or relapsed Waldenström's macroglobulinaemia and required treatment, received up to three cycles of weekly ofatumumab for 5 weeks...
November 30, 2016: Lancet Haematology
https://www.readbyqxmd.com/read/27914701/il-2-anti-il-2-complexes-ameliorate-lupus-nephritis-by-expansion-of-cd4-cd25-foxp3-regulatory-t%C3%A2-cells
#13
Ji-Jing Yan, Jae-Ghi Lee, Joon Young Jang, Tai Yeon Koo, Curie Ahn, Jaeseok Yang
Adoptive transfer of regulatory T cells (Tregs) can delay disease progression and reduce mortality in lupus-prone mice. Here, we tested whether complex (IL-2C) consisting of IL-2 and anti-IL-2 monoclonal antibody (JES6-1) ameliorates lupus nephritis by expanding Tregs as an alternative to problematic Treg infusion therapy. IL-2C treatment of NZB/W F1 mice induced an effective and sustained expansion of CD4(+)CD25(+)Foxp3(+) Tregs in both the kidneys and spleen along with decreased renal infiltration of T cells, B cells, and innate immune cells...
November 30, 2016: Kidney International
https://www.readbyqxmd.com/read/27913543/hemophilia-and-inhibitors-current-treatment-options-and-potential-new-therapeutic-approaches
#14
Shannon L Meeks, Glaivy Batsuli
The immune response to infused factor concentrates remains a major source of morbidity and mortality in the treatment of patients with hemophilia A and B. This review focuses on current treatment options and novel therapies currently in clinical trials. After a brief review of immune tolerance regimens, the focus of the discussion is on preventing bleeding in patients with hemophilia and inhibitors. Recombinant factor VIIa and activated prothrombin complex concentrates are the mainstays in treating bleeds in patients with inhibitors...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913542/new-therapies-for-hemophilia
#15
Steven W Pipe
Individuals with severe hemophilia have benefitted from 5 decades of advances that have led to widespread availability of safe and efficacious factors VIII and IX, a multidisciplinary integrated care model through a network of specialized hemophilia treatment centers, and aggressive introduction of prophylactic replacement therapy to prevent bleeding and preserve joint health. Yet, there are remaining challenges and treatment gaps which have prevented complete abrogation of all joint bleeding, and progressive joint deterioration may continue in some affected individuals over the course of a lifetime...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913524/cellular-and-vaccine-immunotherapy-for-multiple-myeloma
#16
Alfred L Garfall, Edward A Stadtmauer
Allogeneic hematopoietic cell transplantation and donor lymphocyte infusion for multiple myeloma (MM) can induce graft-versus-myeloma immunity and long-term survivorship, but limited efficacy and associated toxicities have prevented its widespread use. Cellular immunotherapies and vaccines seek to induce more specific, reliable, and potent antimyeloma immune responses with less treatment-related risk than is possible with allogeneic transplantation. Advances in molecular biology, and basic and applied immunology, have led to promising approaches such as genetically engineered T cells with chimeric antigen receptors and T-cell receptors targeting myeloma-specific epitopes, vaccine primed ex vivo expanded autologous T cells, expanded marrow-infiltrating lymphocytes, and plasma cell/dendritic cell fusion vaccines...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913463/single-dose-intravenous-iron-for-iron-deficiency-a-new-paradigm
#17
Michael Auerbach, Thomas Deloughery
Iron-deficiency anemia is the most common hematologic problem in the world. Although oral iron is often viewed as front-line therapy, extensive published evidence has accumulated that IV iron is superior, in both efficacy and safety, to oral iron in many clinical situations and should be introduced much sooner in the treatment paradigm of iron-deficient patients. In this chapter, we will review the formulations of IV iron that allow total complete replacement doses in 1 or 2 sessions including practical tips for administration...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913125/apomorphine-therapy-in-parkinson-s-and-future-directions
#18
Nataliya Titova, K Ray Chaudhuri
Apomorphine infusion or injection is an important dopamine agonist non-oral therapy usually used in advanced Parkinson's disease (PD) with refractory motor fluctuations. The drug also has appreciable efficacy for nonmotor fluctuations and is the quickest to reverse predictable "off" periods. Current subcutaneous administration, however, is complicated by problems associated with needle-based therapies, such as skin nodule formation, skin irritation, and avoidance of this treatment option by needle-phobic subjects...
November 30, 2016: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/27912196/nox-isoforms-in-the-development-of-abdominal-aortic-aneurysm
#19
Kin Lung Siu, Qiang Li, Yixuan Zhang, Jun Guo, Ji Youn Youn, Jie Du, Hua Cai
Oxidative stress plays an important role in the formation of abdominal aortic aneurysm (AAA), and we have recently established a causal role of uncoupled eNOS in this severe human disease. We have also shown that activation of NADPH oxidase (NOX) lies upstream of uncoupled eNOS. Therefore, identification of the specific NOX isoforms that are required for eNOS uncoupling and AAA formation would ultimately lead to novel therapies for AAA. In the present study, we used the Ang II infused hph-1 mice to examine the roles of NOX isoforms in the development of AAA...
November 19, 2016: Redox Biology
https://www.readbyqxmd.com/read/27910767/immunostimulatory-effects-of-melphalan-and-usefulness-in-adoptive-cell-therapy-with-antitumor-cd4-t-cells
#20
Michal Kuczma, Zhi-Chun Ding, Gang Zhou
The alkylating agent melphalan is used in the treatment of hematological malignancies, especially multiple myeloma. In the past, the usefulness of melphalan has been solely attributed to its cytotoxicity on fastgrowing cancerous cells. Although the immunomodulatory effects of melphalan were suggested many years ago, only recently has this aspect of melphalan's activity begun to be elucidated at the molecular level. Emerging evidence indicates that melphalan can foster an immunogenic microenvironment by inducing immunogenic cell death (ICD) as characterized by membrane translocation of endoplasmic reticulum protein calreticulin (CRT) and by release of chromatin-binding protein high-mobility group box 1 (HMGB1)...
2016: Critical Reviews in Immunology
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