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David E Rosow, Jamal Ahmed
Importance: Adult laryngotracheal stenosis (LTS) is typically managed surgically, but some patients fail treatment because of rapid restenosis or granulation tissue formation. The need for frequent surgery or tracheostomy reduces the quality of life in these patients and poses a significant challenge for the treating physician. New adjuvant treatments are required to reduce the surgical burden of this condition. Objective: To examine whether patients with rapidly recurrent nonvasculitic LTS who fail surgical management of their stenosis (ie, requiring dilation more frequently than every 6 months) experience longer intervals between surgical procedures when receiving adjuvant treatment with low-dose methotrexate...
October 20, 2016: JAMA Otolaryngology—Head & Neck Surgery
Yinghe Huo, Renske D Veldhuizen, Desiree M van der Heijde, Nick J Besselink, Johannes W G Jacobs, Jacob M van Laar, Max A Viergever, Koen L Vincken, Floris P Lafeber, Maria J H de Hair
OBJECTIVES: To compare as proof of concept the sensitivity to change of automated quantification of radiographic wrist and hand joint space width (JSW) with scoring JSW according to the Sharp/van der Heijde scoring method (SHS) in two strategy groups of a treat-to-target and tight-control early rheumatoid arthritis (RA) study. METHODS: Digital radiographs were assessed for JSW changes of 134 patients of the 236 patients participating in the second Computer Assisted Management in Early Rheumatoid Arthritis trial, of whom both baseline and year 2 radiographs were available (year 1 radiographs n=125)...
September 2016: Clinical and Experimental Rheumatology
Aya Matsuoka, Akira Hirano, Akinori Hattori, Kaoru Ogura, Hiroaki Inoue, Hiroko Yukawa, Shiho Sakaguchi, Natsuko Tanaka, Asaka Kodera, Mari Kamimura, Yoshihiko Naritaka, Tadao Shimizu
A 71-year-old woman diagnosed with left breast cancer underwent mastectomy and axillary dissection in 1987. Pathological findings showed invasive ductal carcinoma that was ER and PgR positive and HER2 negative.5 -FU and tamoxifen were administered for 2 years as adjuvant therapy.Bone metastasis was found in 2002, and endocrine therapy was started, using anastrozole, exemestane, letrozole, medroxyprogesterone acetate, and fulvestrant.However, liver, lung, pleural, penetiral, and lymph-node metastases were observed, and the following chemotherapy regimen was administered: CAF, capecitabine, paclitaxel, vinorelbine, gemcitabine, methotrexate plus mitomycin C, and eribulin...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Claudia Maria Hattinger, Elisa Tavanti, Marilù Fanelli, Serena Vella, Piero Picci, Massimo Serra
Antifolates are structural analogs of folates, which have been used as antitumor drugs for more than 60 years. The antifolate drug most commonly used for treating human tumors is methotrexate (MTX), which is utilized widely in first-line treatment protocols of high-grade osteosarcoma (HGOS). In addition to MTX, two other antifolates, trimetrexate and pemetrexed, have been tested in clinical settings for second-line treatment of recurrent HGOS with patients unfortunately showing modest activity. Areas covered: There is clinical evidence which suggsest that, like other chemotherapeutic agents, not all HGOS patients are equally responsive to antifolates and do not have the same susceptibility to experience adverse drug-related toxicities...
October 19, 2016: Expert Opinion on Drug Metabolism & Toxicology
M C Winter, J A Tidy, A Hills, J Ireson, S Gillett, K Singh, B W Hancock, R E Coleman
OBJECTIVE: To evaluate the outcome of patients treated with second-line chemotherapy for methotrexate-resistant low-risk GTN at the Sheffield Centre, UK between 2001 and 2015, including the novel use of single-agent carboplatin as a strategy to reduce exposure to combination chemotherapy. METHODS: 392 low-risk GTN patients were treated with first-line methotrexate. The selection of chemotherapy regimen following methotrexate-resistance depended on the volume of residual disease as indicated by the serum hCG value at the time, with patients switching to either single-agent dactinomycin at an hCG level<150IU/L from 2001-2010 and <300IU/L since 2010, or to combination treatment with etoposide/dactinomycin (EA) above these thresholds...
October 15, 2016: Gynecologic Oncology
Soumyarwit Manna, James J Augsburger, Zelia M Correa, Marwan F Al-Rjoub, Marepalli B Rao, Rupak K Banerjee
PURPOSE: The purpose of this study is to noninvasively evaluate the safety and toxicity of a chitosan (CS) and polylactic acid (PLA)-based sustained-release methotrexate (MTX) intravitreal microimplant in normal rabbit eyes using electroretinography (ERG). METHODS: PLA-coated CS-based microimplants containing 400 μg of MTX and placebo microimplants (without drug) were surgically implanted in the vitreous of the right and the left eyes, respectively, in each of the 8 New Zealand rabbits using minimally invasive technique...
October 18, 2016: Journal of Ocular Pharmacology and Therapeutics
Hanne Kuitunen, Susanna Tokola, Topi Siniluoto, Matti Isokangas, Eila Sonkajärvi, Seppo Alahuhta, Taina Turpeenniemi-Hujanen, Esa Jantunen, Tapio Nousiainen, Kaija Vasala, Outi Kuittinen
Primary central nervous system lymphoma (PCNSL) is a rare brain tumour with a dismal prognosis. Several phase II studies with high-dose methotrexate-based regimens have shown promising early results, but in all hospital-based data published so far, the disease outcome has been poor. Patients with relapsed or refractory disease have a dismal prognosis. We performed retrospective analysis to evaluate results and tolerabilities of BBBD therapy in combination with high-dose therapy supported by autologous stem cell transplantation...
October 17, 2016: Journal of Neuro-oncology
Vibeke Strand, Eun Bong Lee, Roy Fleischmann, Rieke E Alten, Tamas Koncz, Samuel H Zwillich, David Gruben, Bethanie Wilkinson, Sriram Krishnaswami, Gene Wallenstein
OBJECTIVES: To compare patient-reported outcomes (PROs) in methotrexate (MTX)-naive patients (defined as no prior treatment or ≤3 doses) receiving tofacitinib versus MTX. METHODS: In the 24-month, phase III, randomised, controlled, ORAL Start trial (NCT01039688), patients were randomised 2:2:1 to receive tofacitinib 5 mg two times per day (n=373), tofacitinib 10 mg two times per day (n=397) or MTX (n=186). PROs assessed included Patient Global Assessment of disease (PtGA), pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and health-related quality of life (Short Form-36 [SF-36])...
2016: RMD Open
Tatsuhiro Yamamoto, Kotaro Shikano, Toshihiro Nanki, Shinichi Kawai
We investigated major determinants of the intracellular concentrations of methotrexate polyglutamates (MTXPGs) in patients with rheumatoid arthritis (RA). In 271 RA patients on stable oral low dose weekly pulse MTX therapy, the concentrations of MTXPGs in red blood cells (RBCs) were measured by liquid chromatography-electrospray ionization-tandem mass spectrometry. Polymerase chain reaction-restriction fragment length polymorphism analysis was performed to determine the genotypes of solute carrier family 19 member 1 (SLC19A1), folylpolyglutamate synthase (FPGS), and gamma-glutamyl hydrolase (GGH)...
October 18, 2016: Scientific Reports
Luis Sala-Icardo, Amalia Lamana, Ana María Ortiz, Elena García Lorenzo, Pablo Moreno Fresneda, Rosario García-Vicuña, Isidoro González-Álvaro
OBJECTIVE: To analyze the effect of single nucleotide polymorphisms (SNPs) with well-known functional impact of methylenetetrahydrofolatereductase (MTHFR; rs1801131 and rs1801133), the membrane transporter ABCB1 (rs1045642), the AICAR transformylase/IMP cyclohydrolase (ATIC; rs2372536) and folyl-polyglutamatesynthetase (FPGS; rs1544105), on liver and bone marrow toxicity of methotrexate (MTX). PATIENTS AND METHODS: We analyzed 1415 visits from 350 patients of the PEARL (Princesa Early Arthritis Register Longitudinal) study: (732 with MTX, 683 without MTX)...
October 14, 2016: Reumatología Clinica
Luis Rodriguez-Rodriguez, Leticia Leon, Jose Ivorra-Cortes, Alejandro Gómez, Jose Ramon Lamas, Esperanza Pato, Juan Angel Jover, Lydia Abásolo
OBJECTIVES: To assess the mortality rate (MR) and the mortality risk of a rheumatoid arthritis (RA) inception cohort, with and without biologic agents (BAs). Other factors associated to mortality were also investigated. METHODS: Retrospective longitudinal study of RA patients, attending the rheumatology outpatient clinic of a tertiary Hospital (Madrid), collected over 5 years (2000-2004), and followed from the diagnosis of RA up to the patients' death, lost to follow-up or September 2013...
October 7, 2016: Clinical and Experimental Rheumatology
Gerd Horneff, Ariane Klein, Prasad T Oommen, Anton Hospach, Ivan Foeldvari, Isa Feddersen, Kirsten Minden
OBJECTIVES: While tumour necrosis factor (TNF)-α-inhibitor treatment improved outcome of juvenile idiopathic arthritis (JIA) management markedly, concerns have been raised about an association of TNF-α-inhibitor treatment and an increased risk for malignancies especially lymphoma. METHODS: Cases of suspected malignancies documented in the German Biker Registry are reviewed in detail. RESULTS: Until Dec 31, 2015, 3695 JIA patients were prospectively followed with a total of more than 13,198 observation years...
September 8, 2016: Clinical and Experimental Rheumatology
Bart V J Cuppen, Johannes W G Jacobs, Evert-Jan Ter Borg, Anne C A Marijnissen, Johannes W J Bijlsma, Floris P J G Lafeber, Jacob M van Laar
OBJECTIVES: Despite the success of TNF-alpha inhibitor (TNFi) treatment in rheumatoid arthritis (RA), a substantial number of patients necessitate discontinuation. Prediction thereof would be clinically relevant and guide the decision whether to start TNFi treatment. METHODS: Data were used from the observational BiOCURA cohort, in which patients initiating biological treatment were enrolled and followed up for one year. In the model development cohort (n=192), a model predicting TNFi discontinuation was built using Cox-regression with backward selection (p<0...
October 7, 2016: Clinical and Experimental Rheumatology
Diana Miguel, Susanne Darr-Foit, Jörg Tittelbach, Peter Elsner
No abstract text is available yet for this article.
October 17, 2016: European Journal of Dermatology: EJD
A J Kivitz, S R Gutierrez-Ureña, J Poiley, M C Genovese, R Kristy, K Shay, X Wang, J P Garg, A Zubrzycka-Sienkiewicz
OBJECTIVE: To evaluate efficacy and safety of orally administered once-daily peficitinib in combination with methotrexate (MTX) in patients with moderate-to-severe rheumatoid arthritis (RA) who had an inadequate response to MTX. METHODS: In this multinational, phase IIb, randomized, double-blind, placebo-controlled, dose-ranging trial, patients with RA (N=378) were treated with peficitinib 25 mg, 50 mg, 100 mg, 150 mg + MTX, or matching placebo + MTX once daily for 12 weeks (NCT01554696)...
October 16, 2016: Arthritis & Rheumatology
Marc D Cohen, Edward Keystone
Rituximab is a chimeric monoclonal antibody directed at the CD20 molecule on the surfaces of some but not all B cells. It depletes almost all peripheral B cells, but other niches of B cells are variably depleted, including synovium. Its mechanism of action in rheumatoid arthritis (RA) is only partially understood. Rituximab was efficacious in clinical trials of patients with RA, including those who are methotrexate naïve, those with an incomplete response to methotrexate, and those with an incomplete response to tumor necrosis factor inhibitors...
December 2015: Rheumatol Ther
Philip Mease, Iain B McInnes
INTRODUCTION: Psoriatic arthritis (PsA) is an immune-mediated chronic inflammatory arthropathy associated with impaired physical function and reduced quality of life. Biologic therapies that target tumor necrosis factor (anti-TNF) have significantly improved clinical outcomes. Partial, non- and transient responses remain common comprising significant unmet clinical need. New therapies with novel modes of action are urgently required. OBJECTIVES: The interleukin (IL)-17 pathway has recently been attributed a critical role in the pathogenesis of spondyloarthritides...
June 2016: Rheumatol Ther
Takao Koike, Masayoshi Harigai, Naoki Ishiguro, Shigeko Inokuma, Syuji Takei, Tsutomu Takeuchi, Hisashi Yamanaka, Yoshinari Takasaki, Tsuneyo Mimori, Katsutoshi Hiramatsu, Shuichi Komatsu, Yoshiya Tanaka
INTRODUCTION: There is insufficient evidence regarding the appropriate dose of methotrexate (MTX) required to achieve specific treatment goals in patients with rheumatoid arthritis (RA) receiving biologic drugs in Japan. The present study aimed to assess the dose-response effect of MTX in combination with adalimumab (ADA) to achieve low disease activity (LDA) and/or remission at 24 weeks in RA patients. METHODS: This analysis used data of the ADA all-case survey in Japan (n = 7740), and 5494 patients who received ADA and MTX were classified into five groups by weighted average MTX dose (>0-<4, 4-<6, 6-<8, 8-< 10, and ≥10 mg/week)...
June 2016: Rheumatol Ther
Satoko Hayashi, Katsuya Suzuki, Keiko Yoshimoto, Masaru Takeshita, Takahiko Kurasawa, Kunihiro Yamaoka, Tsutomu Takeuchi
INTRODUCTION: Early prognostic factors for the clinical response in patients with rheumatoid arthritis (RA) after 1 year of treatment with infliximab (IFX) as part of routine clinical practice were investigated. METHODS: Thirty-five patients with RA with an inadequate response to methotrexate were enrolled and administered IFX (3-9 mg/kg, every 4-8 weeks). Serum trough levels of IFX and levels of 9 cytokines were measured at baseline and at 3, 6 months, and 1 year...
June 2016: Rheumatol Ther
Yueqin Han, Yanping Zhu, Jinshen Wang, Yanqin Han, Daogang Qin, Qiaozhi Yang, Xiaojing Sun, Lijun Chen
OBJECTIVES: To investigate the efficacy of interleukin 11 (IL-11) towards the high dose methotrexate (HDMTX)-concurrent rat small intestinal mucositis and its impacts on the proliferation of the human T-lymphoblastic leukemia (CEM) cell line. MATERIALS AND METHODS: 95 Wistar rats were randomly divided into five groups, the normal control group (A), the methotrexate (MTX) control group (B), the IL-11-pre-treated high-dose group (C), the post-IL-11-treatment high-dose group (D) and the post-IL-11-treatment low-dose group (E)...
August 2016: Iranian Journal of Basic Medical Sciences
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