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https://www.readbyqxmd.com/read/29672292/identification-of-risk-factors-in-high-dose-methotrexate-induced-acute-kidney-injury-in-childhood-acute-lymphoblastic-leukemia
#1
Dao-Hai Cheng, Hua Lu, Tao-Tao Liu, Xiao-Qin Zou, Hui-Mei Pang
AIMS: Although high-dose methotrexate (HDMTX) is an effective means for the treatment of acute lymphoblastic leukemia (ALL), the development of renal dysfunction remains a significant management challenge. This study aimed to identify the key factors in HDMTX-induced acute kidney injury (AKI) in childhood ALL. METHODS: We retrospectively analyzed the clinical data in 1,329 courses of HDMTX treatment in 336 Chinese ALL children at the First Affiliated Hospital of Guangxi Medical University from September 2012 to November 2016...
April 19, 2018: Chemotherapy
https://www.readbyqxmd.com/read/29667047/investigation-of-the-mechanism-of-therapeutic-protein-drug-interaction-between-methotrexate-and-golimumab-an-anti-tnf%C3%AE-monoclonal-antibody
#2
Weirong Wang, Jocelyn Leu, Rebecca Watson, Zhenhua Xu, Honghui Zhou
A prominent example of human therapeutic protein-drug interaction (TP-DI) is between methotrexate (MTX) and anti-TNFα mAbs. One plausible mechanism for this TP-DI is through the pharmacodynamic effect of MTX on immunogenicity. However, there is no definitive evidence to substantiate this mechanism, and other competing hypotheses, such as MTX suppressing FcγRI expression thereby affecting mAb PK, have also been proposed. In order to understand this mechanism, a cynomolgus monkey study was conducted using golimumab as a model compound...
April 17, 2018: AAPS Journal
https://www.readbyqxmd.com/read/29665911/-clinical-analysis-of-refractory-primary-central-nervouse-system-lymphoma-treated-with-high-dose-mtx-based-chemotherapy-and-haploidentical-hematopoietic-stem-cell-infusion
#3
Juan Liu, Wan-Jun Sun, Xiao-Qin Xi, Xiao-Mei Huang, Xiao-Xi Li, Jiao Xia, Yuan-Yuan Qu
OBJECTIVE: To investigate the efficacy and safety of high-dose methotrexate-based chemotherapy combined with granulocyte-colony stimulating factor (G-CSF)-mobilized family related haploidentical donor peripheral blood hematopoietic stem cell (G-PBHSC) infusion for the treatment of patients with refractory primary central nervouse system lymphoma (PCNSL). METHODS: Three patients with refractory PCNSL were treated in Department of Hematology of the General Hospital of the PLA's Rocket Force from March 2014 to September 2015...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29664819/risk-factors-for-pneumocystis-jirovecii-pneumonia-in-patients-with-rheumatoid-arthritis-and-a-prophylactic-indication-of-trimethoprim-sulfamethoxazole
#4
Kazutoshi Yukawa, Yasutsugu Nagamoto, Hirofumi Watanabe, Masamoto Funaki, Mitsuhiro Iwahashi, Jiro Yamana, Rie Sasaki, Seizo Yamana
BACKGROUND/OBJECTIVES: Immunosuppressant medications (ISPs) increase the occurrence of Pneumocystis jirovecii pneumonia (PCP) in rheumatoid arthritis (RA) patients. The prophylactic administration of trimethoprim/sulfamethoxazole (TMP/SMX) for PCP is effective but has serious adverse effects and so should be selectively used for patients at high risk. The aims of this study were to clarify the risk factors for PCP in RA patients and to establish the indications for administering TMP/SMX...
April 17, 2018: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
https://www.readbyqxmd.com/read/29651915/intravenous-radiographic-contrast-administered-prior-to-high-dose-methotrexate-and-subsequent-toxicity-requiring-the-use-of-glucarpidase
#5
Thomas E Schultz, Alia C Lynch
Methotrexate is a dihydrofolate reductase inhibitor that interferes with DNA synthesis, DNA repair, and cellular replication. We present the first adult case of a patient who received intravenous contrast prior to administration of high-dose methotrexate, who subsequently experienced delayed methotrexate clearance and renal impairment necessitating the use of glucarpidase. This case displays a possible correlation between intravenous radiographic contrast administration and resulting toxicity due to delayed methotrexate clearance...
January 1, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29626002/evaluating-off-label-uses-of-acetazolamide
#6
REVIEW
Megan A Van Berkel, Jessica L Elefritz
PURPOSE: Current off-label uses of acetazolamide in hospitalized patients are reviewed. SUMMARY: Acetazolamide is a carbonic anhydrase inhibitor typically used for indications including epilepsy, glaucoma, edema, and altitude sickness but it may be prescribed in hospitalized patients for off-label indications. It inhibits carbonic anhydrase, which leads to reduced hydrogen ion secretion in the proximal renal tubule, resulting in increased bicarbonate and cation excretion and causing urinary alkalization and diuresis...
April 15, 2018: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/29621124/therapeutic-drug-monitoring-of-methotrexate-in-plasma-using-u-hplc-ms-ms-necessary-after-administration-of-glucarpidase-in-methotrexate-intoxications
#7
Midas B Mulder, Ruud Huisman, Frederike K Engels, Inge M van der Sluis, Birgit C P Koch
High-dose methotrexate (HD-MTX) is used to treat a variety of cancers. In all patients receiving HD-MTX, plasma MTX levels are monitored mainly to anticipate rescue therapy to prevent adverse events. We present two children treated with HD-MTX and afterward treated with glucarpidase at different time-points after their HD-MTX infusions. After the administration of glucarpidase, a non-toxic metabolite of MTX cross-reacts with MTX in the standard immunoassay (Abbott Diagnostics, Hoofddorp, The Netherlands) resulting in an artificially elevated MTX level...
April 3, 2018: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/29606256/-renal-toxicity-of-high-dose-methotrexate
#8
Hugo Garcia, Véronique Leblond, François Goldwasser, Didier Bouscary, Emmanuel Raffoux, Nicolas Boissel, Sophie Broutin, Dominique Joly
INTRODUCTION: High-dose methotrexate (at least 1g/m2 ) is used to treat haematologic malignancies and osteosarcomas. Acute kidney injury is a well-known adverse-event after high-dose methotrexate and may lead to delayed drug elimination. Besides usual therapeutics (hyperhydration, urine alkalinisation, leucovorin rescue, renal replacement therapy), a costly specific enzymatic treatment (glucarpidase) is now available but its clinical impact remains elusive. PATIENTS AND METHODS: We analysed high-dose methotrexate prescription charts in 11 clinical centres during the last 15 years to identify and describe adult patients who developed acute kidney injury (according to KDIGO classification)...
April 2018: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/29605422/leukocytoclastic-vasculitis-and-desensitization-to-high-dose-methotrexate-in-primary-central-nervous-system-lymphoma
#9
Colette Hanna, Diego Villa, Carla Irani, Marwan Ghosn, Elie El Rassy
No abstract text is available yet for this article.
March 19, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29604975/primary-cns-lymphoma-in-hiv-infection
#10
Dieta Brandsma, Jacoline E C Bromberg
Primary CNS lymphoma (PCNSL) has been designated an acquired immune deficiency syndrome (AIDS)-defining disease since 1983 and accounts for up to 15% of non-Hodgkin lymphomas in human immunodeficiency virus (HIV) patients. The majority of HIV patients are Epstein-Barr virus (EBV)-related. The most likely etiology is ineffective immunoregulation of EBV, inducing oncogenic protein expression, and subsequent loss of apoptosis and increased proliferation of lymphocytes. PCNSL generally presents with supratentorial, single or multiple, contrast-enhancing lesions...
2018: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29599672/the-effect-of-subcutaneous-methotrexate-on-markers-of-metabolic-syndrome-in-psoriatic-patients-preliminary-report
#11
Agnieszka Owczarczyk-Saczonek, Marek Drozdowski, Agata Maciejewska-Radomska, Dariusz Choszcz, Waldemar Placek
Introduction: Methotrexate (MTX) has anti-proliferative and anti-inflammatory effects in psoriasis. Moreover, low doses can reduce the risk of developing cardiovascular diseases. It turns out that psoriasis and atherosclerosis have a similar pathogenetic mechanism: the same pro-inflammatory cytokines, Th1 and Th17, are involved in both diseases. Aim: To evaluate the effects of metabolic markers, protective cytokines (interleukin 10 (IL-10), transforming growth factor β (TGF-β)) and a marker of endothelial damage (endocan) in patients with plaque psoriasis...
February 2018: Postȩpy Dermatologii i Alergologii
https://www.readbyqxmd.com/read/29596541/association-of-cerebrospinal-fluid-biomarkers-of-central-nervous-system-injury-with-neurocognitive-and-brain-imaging-outcomes-in-children-receiving-chemotherapy-for-acute-lymphoblastic-leukemia
#12
Yin Ting Cheung, Raja B Khan, Wei Liu, Tara M Brinkman, Michelle N Edelmann, Wilburn E Reddick, Deqing Pei, Angela Panoskaltsis-Mortari, Deokumar Srivastava, Cheng Cheng, Leslie L Robison, Melissa M Hudson, Ching-Hon Pui, Kevin R Krull
Importance: Little is known about treatment-related neurotoxic mechanisms in children with acute lymphoblastic leukemia (ALL) treated with chemotherapy only. Objective: To examine concentration of cerebrospinal fluid (CSF) biomarkers of brain injury at ALL diagnosis and during cancer therapy and to evaluate associations with long-term neurocognitive and neuroimaging outcomes and relevant genetic polymorphisms. Design, Setting, and Participants: This prospective cohort study included 235 patients with ALL who received a chemotherapy-only protocol...
March 29, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29581608/physical-compatibility-of-micafungin-with-sodium-bicarbonate-hydration-fluids-commonly-used-with-high-dose-methotrexate-chemotherapy
#13
Logan C Joiner, Clay Tynes, John Arnold, Rachel R Miller, Greg Gorman
Purpose: The purpose of this study was to determine the physical compatibility of micafungin with commonly used concentrations of sodium bicarbonate hydration fluids administered via a Y-site connected to a central venous catheter (Y-site/CVC). Methods: Micafungin sodium (evaluated concentration of 1.5 mg/mL) was combined in a 3:1 (vehicle:drug) ratio with the following commonly used hydration vehicles: 40 mEq/L sodium bicarbonate in 5% dextrose in water with ¼ normal saline (40SB-D5W-1/4NS), 75 mEq/L sodium bicarbonate in D5W (75SB-D5W), and 154 mEq/L sodium bicarbonate in D5W (154SB-D5W)...
April 2018: Hospital Pharmacy
https://www.readbyqxmd.com/read/29574622/similar-improvements-in-patient-reported-outcomes-among-rheumatoid-arthritis-patients-treated-with-two-different-doses-of-methotrexate-in-combination-with-adalimumab-results-from-the-musica-trial
#14
Gurjit S Kaeley, Daryl K MacCarter, Janak R Goyal, Shufang Liu, Kun Chen, Jennifer Griffith, Hartmut Kupper, Vishvas Garg, Jasmina Kalabic
INTRODUCTION: In patients with rheumatoid arthritis (RA), combination treatment with methotrexate (MTX) and adalimumab is more effective than MTX monotherapy. From the patients' perspective, the impact of reduced MTX doses upon initiating adalimumab is not known. The objective was to evaluate the effects of low and high MTX doses in combination with adalimumab initiation on patient-reported outcomes (PROs), in MTX-inadequate responders (MTX-IR) with moderate-to-severe RA. METHODS: MUSICA was a randomized, double-blind, controlled trial evaluating the efficacy of 7...
March 24, 2018: Rheumatology and Therapy
https://www.readbyqxmd.com/read/29566769/effectiveness-and-safety-of-tofacitinib-in-rheumatoid-arthritis-a-cohort-study
#15
Marina Amaral de Ávila Machado, Cristiano Soares de Moura, Steve Ferreira Guerra, Jeffrey R Curtis, Michal Abrahamowicz, Sasha Bernatsky
BACKGROUND: Tofacitinib is the first oral Janus kinase inhibitor approved for the treatment of rheumatoid arthritis (RA). We compared the effectiveness and safety of tofacitinib, disease-modifying antirheumatic drugs (DMARDs), tumor necrosis factor inhibitors (TNFi), and non-TNF biologics in patients with RA previously treated with methotrexate. METHODS: We used MarketScan® databases (2011-2014) to study methotrexate-exposed patients with RA who were newly prescribed tofacitinib, DMARDs other than methotrexate, and biologics...
March 23, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29558044/efficacy-and-safety-of-golimumab-as-add-on-therapy-to-standard-disease-modifying-antirheumatic-drugs-results-of-the-go-more-study-in-the-polish-population
#16
Sławomir Jeka, Bogdan Batko, Mariusz Korkosz, Maria Majdan, Brygida Kwiatkowska, Iwona Dankiewicz-Fares, Jerzy M Sobiecki, Włodzimierz Samborski
BACKGROUND: The GO-MORE study was an open-label, multinational, prospective study that investigated the efficacy and safety of adding golimumab to synthetic disease-modifying antirheumatic drugs (sDMARDs) in patients with active rheumatoid arthritis (RA). OBJECTIVES: The aim of this study was to assess the efficacy and safety of golimumab add-on therapy in the Polish subpopulation of the GO-MORE study. MATERIAL AND METHODS: Patients were administered 50 mg subcutaneous doses of golimumab once a month for 6 months, while continuing therapy with sDMARDs and/or glucocorticoids (GCS)...
March 20, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29548055/primary-central-nervous-system-lymphoma
#17
Sarah Löw, Tracy T Batchelor
Primary central nervous system lymphoma (PCNSL) is an extranodal non-Hodgkin lymphoma limited to the brain, spinal cord, leptomeninges, and eyes. The majority of patients are immunocompetent, with a median age of 65 years at diagnosis. Historically, whole-brain radiation therapy (WBRT) was the first and sole treatment for PCNSL. Today, due to the recognized neurotoxicity of WBRT, this modality is usually avoided in the treatment. Most chemotherapy regimens are based on high-dose methotrexate plus the anti-CD20 monoclonal antibody rituximab, leading to high response rates, but 5-year survival is still poor at approximately 30% compared with other extranodal lymphomas...
February 2018: Seminars in Neurology
https://www.readbyqxmd.com/read/29545912/more-severe-toxicity-of-genetic-polymorphisms-on-mthfr-activity-in-osteosarcoma-patients-treated-with-high-dose-methotrexate
#18
Lu Xie, Wei Guo, Yi Yang, Tao Ji, Jie Xu
5,10-Methylenetrahydrofolate reductase (MTHFR), a key enzyme for folate metabolism, catalyses the irreversible conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which is located at the end of the short arm (1p36.3). Two common non-synonymous variants, the C677T (Ala222Val) and A1298C (Glu429Ala), were mainly described with decreased enzymatic activity and an alteration of intracellular folate distribution. Osteosarcomas are currently treated with high dose of methotrexate (MTX). The decreased enzyme activity of MTHFR theoretically could increase the drug action of MTX and at the same time increase toxic and side effect...
February 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29542345/epratuzumab-for-the-treatment-of-systemic-lupus-erythematosus
#19
Daniel Geh, Caroline Gordon
Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease. There are three drugs licensed for the treatment of lupus: corticosteroids, hydroxychloroquine and belimumab. Immunosuppressants such as azathioprine, methotrexate and mycophenolate are also used. Despite these treatments there is still considerable morbidity. New treatments are needed for the management of active lupus. Epratuzumab a humanized IgG1 monoclonal antibody that targets CD22 resulting in selective B cell modulation that has been considered a potential treatment for SLE...
March 20, 2018: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/29541561/evaluation-identification-and-management-of-acute-methotrexate-toxicity-in-high-dose-methotrexate-administration-in-hematologic-malignancies
#20
REVIEW
Doron Feinsilber, Roberto J Leoni, Duminda Siripala, Julianne Leuck, Katrina A Mears
The pharmacological and medical management of complex chemotherapy regimens are vast and complex, requiring an intimate understanding of physiology, particularly when novel biologic agents are utilized with commonly used regimens. The molecular classification in patients with diffuse large B-cell lymphoma (DLBCL) is multifaceted, particularly with the expansion of novel molecular targets. The pharmacological and medical management of hematologic malignancies with a tendency to have central nervous system (CNS) involvement is complex and requires an understanding of physiology and pharmacology...
January 8, 2018: Curēus
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