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1.
Int Heart J ; 61(5): 1005-1013, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32999188

RESUMO

This study sought to evaluate clinical features, treatment patterns, and outcomes of patients with idiopathic inflammatory myopathy (IIM) complicated by heart failure (HF). Thirty-two patients with IIM-HF admitted to the Peking Union Medical College Hospital between January 1999 and January 2018 were retrospectively reviewed, including 14 patients with polymyositis, 11 with dermatomyositis, and 7 with overlap syndrome. Survivors and no-survivors were compared on clinical characteristics and treatment. Although systemic symptoms were variable, all patients presented with elevated troponin I. Rapid atrial arrhythmia was the most frequent arrhythmia. Systolic dysfunction and restrictive diastolic dysfunction were typical presentations in echocardiography. Twenty-nine patients were followed up for a median of 2.8 years (0.1 month to 11 years). We recorded 13 deaths of cardiogenic cause, 1 of serious IIM, and 3 of infective complications. The median survival time from diagnosis of IIM-HF to all-cause mortality was 8.4 months (range from 1 month to 5 years). Both all-cause deaths and cardiogenic deaths were more reported in the methotrexate-alone group than in the combination therapy group (6/7 versus 3/10, P = 0.050; 5/6 versus 2/9, P = 0.041). Combination therapy including methotrexate (HR = 0.188, 95%CI 0.040-0.871, P = 0.033) and taking ß-receptor blockers (HR = 0.249, 95%CI 0.086-0.719, P = 0.010) was associated with reduced risk of all-cause deaths. In conclusion, elevated troponin I, atrial arrhythmia, and systolic and restrictive diastolic dysfunction are typical characteristics of IIM-HF. Combined immunosuppression that includes methotrexate and ß-receptor blockers seems to be important to improve survival.


Assuntos
Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Miosite/tratamento farmacológico , Miosite/mortalidade , Adolescente , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , China/epidemiologia , Quimioterapia Combinada , Feminino , Glucocorticoides/uso terapêutico , Insuficiência Cardíaca/etiologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Miosite/complicações , Estudos Retrospectivos , Adulto Jovem
2.
Zhonghua Zhong Liu Za Zhi ; 42(8): 692-696, 2020 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-32867464

RESUMO

Objective: To evaluate the efficacy and safety of polyethylene glycol liposome doxorubicin (PLD) in the treatment of osteosarcoma. Methods: This study was a single-center retrospective clinical study. Two hundreds and seventy-six classical osteosarcoma treated in Beijing Jishuitan Hospital from 2015 to 2016 were enrolled. There were 213 patients who received combined chemotherapy of high dose methotrexate, ifosfamide, cisplatin and doxorubicin (ADM) were classified in ADM group. Other 63 patients received the same types, doses and cycles of chemotherapy drugs except ADM replaced by PLD were identified as PLD group. Clinical and imaging evaluation and surgical treatment were performed after neoadjuvant chemotherapy. Tumor necrosis rate was examined according to Huvos method. The efficacy of neoadjuvant chemotherapy was evaluated based on 90% necrosis rate. The recurrence, metastasis and survival were followed up regularly after operation. The adverse reactions of hematology, hepatorenal toxicity, gastrointestinal reaction and cardiotoxicity were evaluated. Results: There were no significant differences between PLD group and ADM group in age, sex, location, stage and surgical margin (all P>0.05). There were no significant differences in clinical symptoms and imaging evaluation between PLD group and ADM group after preoperative chemotherapy (all P>0.05). The tumor necrosis rate was detected in 134 cases. Among 27 cases of PLD group, tumor necrosis rates more than 90% were 11 cases, while among 107 cases of ADM group, tumor necrosis rates more than 90% were 45 cases. No significant difference of tumor necrosis rate between this two group was observed (P=0.901). The recurrence rates of PLD group and ADM group were 7.8% (4/51) and 7.3% (12/164), the metastasis rates were 19.6% (10/51) and 16.5% (27/164), the median progression free survival (PFS) were 42 and 37 months, respectively, without significant differences (all P>0.05). The incidence of granulocytopenia and decrease degree of granulocytes in PLD group were significantly lower than those in ADM group (P<0.001). There were no significant differences in the incidences of thrombocytopenia, anemia, gastrointestinal reaction, liver function damage and stomatitis between two groups (all P>0.05). Conclusions: PLD and ADM have similar chemotherapeutic effects in osteosarcoma. The incidences of adverse reactions of PLD are lower, especially the hematological toxicity represented by granulocytopenia is significantly reduced. PLD has a better application prospect.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/terapia , Lipossomos/uso terapêutico , Osteossarcoma/tratamento farmacológico , Neoplasias Ósseas/patologia , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Extremidades , Humanos , Ifosfamida/administração & dosagem , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Recidiva Local de Neoplasia , Osteoblastos/efeitos dos fármacos , Osteoblastos/patologia , Osteossarcoma/patologia , Polietilenoglicóis , Prognóstico , Estudos Retrospectivos
3.
Medicine (Baltimore) ; 99(39): e22335, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991445

RESUMO

INTRODUCTION: Plasmablastic lymphoma (PBL) is an uncommon and aggressive large B-cell lymphoma commonly diagnosed in human immunodeficiency viruses -positive patients. Oral cavity is the most commonly PBL affected site. Most oral PBLs presented as asymptomatic swellings, frequently associated with ulcerations and bleeding. Most cases lacked B-symptoms, suggesting a more local involvement of the disease. No standard treatment is yet for oral PBL. Five-year survival rate recorded no more than 33.5%. PATIENT CONCERNS: A 39-year-old male presented to Dental Clinic with 1 month swelling of the oral cavity, in absence of any other symptoms or signs. He followed antibiotic therapy just on suspicion of an oral abscess and later oral surgical treatment on suspicion of bone neoplasm. DIAGNOSIS: Surgical specimen analysis highlighted a diffuse infiltrate of large-sized atypical cells with plasmablastic appearance and plasma cell phenotype. Oral cavity PBL was diagnosed. Blood tests recorded mild lymphopenia and positive human immunodeficiency viruses serology. INTERVENTIONS: Patient underwent chemotherapy including intrathecal methotrexate prophylaxis, in addition to a highly active antiretroviral therapy. OUTCOMES: At 12 months from diagnosis, patient recorded complete hematological remission. CONCLUSIONS: Oral PBL diagnosis requires a high level of suspicion and awareness both by physicians and pathologists. They should be aware of the extent of such disease which is often mistaken as oral abscess or infected tooth, thus leading to delay the most appropriate diagnostic evaluation. As PBL is an aggressive non-Hodgkin lymphoma, a delayed diagnosis might negatively impact on both treatment and survival.


Assuntos
Antineoplásicos/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Boca/patologia , Linfoma Plasmablástico/tratamento farmacológico , Abscesso/diagnóstico , Abscesso/tratamento farmacológico , Adulto , Assistência ao Convalescente , Antibacterianos/uso terapêutico , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , Quimioterapia Combinada , Edema/etiologia , Infecções por HIV/complicações , Soropositividade para HIV/sangue , HIV-1/imunologia , Humanos , Injeções Espinhais , Linfoma não Hodgkin/patologia , Masculino , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Plasmócitos/patologia , Linfoma Plasmablástico/diagnóstico por imagem , Resultado do Tratamento
4.
Georgian Med News ; (304-305): 95-99, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32965257

RESUMO

The aim of the research was to determine liver lesion in patients with Oligoarticular and RF-negative Polyarticular forms of JIA by noninvasive methods depending on duration of Methotrexate treatment. The study included 42 patients with Rheumatoid factor (RF) negative oligo- and polyarticular joints forms of JIA from 3 to 18 years old. They were investigated by measurement of alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), haptoglobin, triglycerides, gamma glutamine transferase (GGT), apolipoprotein-A (Apo-A), a2-macroglobulin, cholesterine levels. The equation for calculating the FibroTest score regression coefficient had been done according U.S. patent 6.631.330. Student -Fisher Test, Mann - Whitney U-test were used for the statistical processing. In spite of MTX treatment progression of JIA was determined according assessment of joints functional class and radiological stage (p<0.05). Increased level of ALAT was prominent (40%) in children taken MTX for 1-5 years in comparison with other studied patients (p<0.05). 17 % of children who took MTX longer than 5 years had increased GGT content. Metabolic liver function was not changed because levels of Apo-A, haptoglobin, total bilirubin, cholesterine were within normal limits due to all stages of MTX taking. The increased level of a2-macroglobulin as a predictor of liver fibrosis was determined in all studying groups with the average frequency 36 % and it did not correspond to the duration of MTX treatment. According FibroTest score regression 14% of patients had liver fibrosis F1, which did not depend on duration of MTX treatment. According to our findings, patients using MTX for JIA management had joint damage progresses despite usage of MTX. Hepatic cytolysis is most frequently appeared within 15 years of MTX taking. Risk of liver fibrosis does not depend on duration of MTX treatment.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Neoplasias Hepáticas , Adolescente , Alanina Transaminase , Criança , Pré-Escolar , Humanos , Metotrexato/uso terapêutico , Resultado do Tratamento
5.
PLoS Med ; 17(9): e1003296, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32960885

RESUMO

BACKGROUND: Based on different genetic and environmental risk factors and histology, it has been proposed that rheumatoid arthritis (RA) consists of 2 types: autoantibody-positive and autoantibody-negative RA. However, until now, this remained hypothetical. To assess this hypothesis, we studied whether the long-term outcomes differed for these 2 groups of RA patients. METHODS AND FINDINGS: In the Leiden Early Arthritis Clinic cohort, 1,285 consecutive RA patients were included between 1993 and 2016 and followed yearly. Treatment protocols in routine care improved over time, irrespective of autoantibody status, and 5 inclusion periods were used as instrumental variables: 1993-1996, delayed mild disease-modifying antirheumatic drug (DMARD) initiation (reference period); 1997-2000, early mild DMARDs; 2001-2005, early methotrexate; 2006-2010, early methotrexate followed by treat-to-target adjustments; 2011-2016, similar to 2006-2010 plus additional efforts for very early referral. Three long-term outcomes were studied: sustained DMARD-free remission (SDFR) (persistent absence of clinical synovitis after DMARD cessation), mortality, and functional disability measured by yearly Health Assessment Questionnaire (HAQ). Treatment response in the short term (disease activity) was measured by Disease Activity Score-28 with erythrocyte sedimentation rate (DAS28-ESR). Linear mixed models and Cox regression were used, stratified for autoantibody positivity, defined as IgG anti-CCP2 and/or IgM rheumatoid factor positivity. In total, 823 patients had autoantibody-positive RA (mean age 55 years, 67% female); 462 patients had autoantibody-negative RA (age 60 years, 64% female). Age, gender, and percentage of autoantibody-positive patients were stable throughout the inclusion periods. Disease activity significantly decreased over time within both groups. SDFR rates increased after introduction of treat-to-target (hazard ratio [HR] 2006-2010 relative to 1993-1996: 3.35 [95% CI 1.46 to 7.72; p = 0.004]; HR 2011-2016: 4.57 [95% CI 1.80 to 11.6; p = 0.001]) in autoantibody-positive RA, but not in autoantibody-negative RA. In autoantibody-positive RA, mortality decreased significantly after the introduction of treat-to-target treatment adjustments (HR 2006-2010: 0.56 [95% CI 0.34 to 0.92; p = 0.023]; HR 2011-2016: 0.33 [95% CI 0.14 to 0.77; p = 0.010]), but not in autoantibody-negative RA (HR 2006-2010: 0.79 [95% CI 0.40 to 1.56; p = 0.50]; HR 2011-2016: 0.36 [95% CI 0.10 to 1.34; p = 0.13]). Similarly, functional disability improved in autoantibody-positive RA for the periods after 2000 relative to 1993-1996 (range -0.16 [95% CI -0.29 to -0.03; p = 0.043] to -0.32 [95% CI -0.44 to -0.20; p < 0.001] units of improvement), but not in autoantibody-negative RA (range 0.10 [95% CI -0.12 to 0.31; p = 0.38] to -0.13 [95% CI -0.34 to 0.07; p = 0.20] units of improvement). Limitations to note were that treatment was not randomized-but it was protocolized and instrumental variable analysis was used to obtain comparable groups-and that a limited spread of ethnicities was included. CONCLUSIONS: Although disease activity has improved in both autoantibody-positive and autoantibody-negative RA in recent decades, the response in long-term outcomes differed. We propose that it is time to subdivide RA into autoantibody-positive RA (type 1) and autoantibody-negative RA (type 2), in the hope that this leads to stratified treatment in RA.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/genética , Adulto , Idoso , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Autoanticorpos/genética , Autoanticorpos/imunologia , Biomarcadores Farmacológicos/sangue , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Índice de Gravidade de Doença
6.
Rheumatol Int ; 40(11): 1741-1751, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32880032

RESUMO

Repurposing of antirheumatic drugs has garnered global attention. The aim of this article is to overview available evidence on the use of widely used antirheumatic drugs hydroxychloroquine, methotrexate and colchicine for additional indications. Hydroxychloroquine has endothelial stabilizing and anti-thrombotic effects. Its use has been explored as an adjunctive therapy in refractory thrombosis in antiphospholipid syndrome. It may also prevent recurrent pregnancy losses in the absence of antiphospholipid antibodies. Hydroxychloroquine favourably modulates atherogenic lipid and glycaemic profiles. Methotrexate has been tried for modulation of cardiovascular events in non-rheumatic clinical conditions, although a large clinical trial failed to demonstrate a benefit. Colchicine has been shown to successfully reduce the risk of recurrent cardiovascular events in a large multicentric trial. Potential antifibrotic effects of colchicine require further exploration. Hydroxychloroquine, methotrexate and colchicine are also being tried at different stages of the ongoing Coronavirus Disease 19 (COVID-19) pandemic for prophylaxis and treatment. While the use of these agents is being diversified, their adverse effects should be timely diagnosed and prevented. Hydroxychloroquine can cause retinopathy and rarely cardiac and auditory toxicity, retinopathy being dose and time dependent. Methotrexate can cause transaminitis, cytopenias and renal failure, particularly in acute overdoses. Colchicine can rarely cause myopathies, cardiomyopathy, cytopenias and transaminitis. Strong evidence is warranted to keep balance between benefits of repurposing these old antirheumatic drugs and risk of their adverse effects.


Assuntos
Antirreumáticos/uso terapêutico , Betacoronavirus , Colchicina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Reposicionamento de Medicamentos , Hidroxicloroquina/uso terapêutico , Metotrexato/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Colchicina/efeitos adversos , Hidroxicloroquina/efeitos adversos , Metotrexato/efeitos adversos , Pandemias
7.
Brasília; s.n; 5 ago 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1117760

RESUMO

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 11 artigos e 6 protocolos.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Antivirais/uso terapêutico , Avaliação da Tecnologia Biomédica , Imunoglobulinas/uso terapêutico , Metilprednisolona/uso terapêutico , Colchicina/uso terapêutico , Metotrexato/uso terapêutico , Estudos de Coortes , Interferons/uso terapêutico , Corticosteroides/uso terapêutico , Azitromicina/uso terapêutico , Oseltamivir/uso terapêutico , Células-Tronco Mesenquimais , Interferon alfa-2/uso terapêutico , Glucocorticoides/uso terapêutico , Hidroxicloroquina/uso terapêutico , Imunossupressores/uso terapêutico , Antibacterianos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico
9.
Medicine (Baltimore) ; 99(31): e21432, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756152

RESUMO

INTRODUCTION: A cesarean scar pregnancy (CSP), when combined with an arteriovenous malformation (AVM), is a rare, but potentially life-threatening condition that may be associated with uncontrolled hemorrhage. Hysterectomy is indicated when conservative treatment fails. Preservation of fertility is challenging. PATIENT CONCERNS: We reported a 33-year-old woman with a CSP combined with an AVM who failed methotrexate administration as conservative treatment. DIAGNOSES: A CSP combined with an AVM was diagnosed via three-dimensional color Doppler angiogram and magnetic resonance imaging. INTERVENTIONS: Transvaginal removal of the ectopic gestation and repair of the uterine defect was performed without incident. OUTCOMES: The fertility of the patient was preserved and hysterectomy was avoided. CONCLUSION: Transvaginal fertility-sparing surgery may be successfully performed to prevent hysterectomy when conservative treatment fails in patients with a CSP combined with an AVM.


Assuntos
Malformações Arteriovenosas/complicações , Malformações Arteriovenosas/cirurgia , Cicatriz/patologia , Preservação da Fertilidade/métodos , Adulto , Angiografia/métodos , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , Malformações Arteriovenosas/diagnóstico por imagem , Malformações Arteriovenosas/tratamento farmacológico , Cesárea/efeitos adversos , Cicatriz/cirurgia , Feminino , Humanos , Imageamento Tridimensional/métodos , Imagem por Ressonância Magnética/métodos , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Gravidez , Gravidez Ectópica/cirurgia , Resultado do Tratamento , Ultrassonografia Doppler em Cores/métodos
10.
Int J Nanomedicine ; 15: 4763-4778, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32753865

RESUMO

Introduction: Methotrexate exhibits poor cutaneous bioavailability and systemic side effects on topical administration, so there is an unmet need for a novel carrier and its optimized therapy. Methotrexate-loaded nanostructured lipid carriers (MTXNLCs) were formulated and characterized to determine in vitro drug release and evaluate the role of MTXNLC gel in the topical treatment of psoriasis. Methods: A solvent diffusion technique was employed to prepare MTXNLCs, which was optimized using 32 full factorial designs. The mean diameter and surface morphology of MTXNLCs was evaluated. The crystallinity of lyophilized MTXNLCs was characterized by differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD). MTXNLCs were integrated in 1% w/w Carbopol 934 P gel base, and in vitro skin deposition studies in human cadaver skin (HCS) were carried out. Results: The optimized MTXNLCs were rod-shaped, with an average particle size of 253 ± 8.65 nm, a zeta potential of -26.4±0.86 mV, and EE of 54.00±1.49%. DSC and XRD data confirmed the formation of NLCs. Significantly higher deposition of MTX was found in HCS from MTXNLC gel (71.52 ±1.13%) as compared to MTX plain gel (38.48±0.96%). In vivo studies demonstrated significant improvement in therapeutic response and reduction in local side effects with MTXNLCs-loaded gel in the topical treatment of psoriasis. Anti-psoriatic efficacy of MTXNLCs 100 ug/cm2 compared with plain MTX gel was evaluated using imiquimod (IMQ)-induced psoriasis in BALB/c mice. The topical application of MTXNLCs to the mouse ear resulted in a significant reduction of psoriatic area and severity index, oxidative stress, inflammatory cytokines like TNF-α, IL-1ß, and IL-6 and IMQ-induced histopathological alterations in mouse ear samples. Conclusion: Developed formulation of MTXNLC gel demonstrated better anti-psoriatic activity and also displayed prolonged and sustained release effect, which shows that it can be a promising alternative to existing MTX formulation for the treatment of psoriasis.


Assuntos
Composição de Medicamentos , Géis/química , Imiquimode/uso terapêutico , Inflamação/tratamento farmacológico , Lipídeos/química , Metotrexato/uso terapêutico , Nanoestruturas/química , Psoríase/tratamento farmacológico , Administração Cutânea , Administração Tópica , Animais , Catalase/metabolismo , Citocinas/metabolismo , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Glutationa/metabolismo , Humanos , Inflamação/patologia , Malondialdeído/metabolismo , Camundongos Endogâmicos BALB C , Nanoestruturas/ultraestrutura , Tamanho do Órgão , Superóxido Dismutase/metabolismo
11.
PLoS One ; 15(8): e0237143, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760165

RESUMO

OBJECTIVES: Abatacept acts as a competitive inhibitor of the CD28/(CD80/86) costimulation signal required for T cell activation. Mechanisms of action of abatacept have not been fully investigated. The objective of this study was to provide detailed insight into the mode of action of Abatacept based on gene expression data. METHODS: In this ancillary study from the APPRAISE trial, we investigated the global molecular effects of Abatacept in whole blood samples collected prospectively in biologic naive rheumatoid arthritis patients (n = 19) at baseline and 6 months after the initiation of Abatacept therapy concomitant with methotrexate. Whole human genome microarrays (4x44K) were performed on both baseline and 6-month samples from responders and non-responders patients categorized according to EULAR criteria. T-test with Benjamini-Hochberg correction was performed to identify significant gene expression changes. Gene Ontology and Single Experiment Analysis tools allowed us to highlight specific biological mechanisms involved in methotrexate/Abatacept. RESULTS: In methotrexate/Abatacept responders, 672 genes were significantly (q<0.05) dysregulated at 6 months compared to baseline. Correlation analysis highlighted 19 genes whose dysregulations were significantly associated with disease activity variation (p<0.05) and whose functions were associated with proliferation, apoptosis of cells and mitochondrial metabolism, suggesting a restoration of oxidative signaling. The other 653 gene expression changes were relative to direct or indirect effects of methotrexate/Abatacept treatment and were significantly (p<0.005) involved in pathways relative to mRNA processing, proteasome, angiogenesis, apoptosis and TCR signaling. This study highlights new mechanisms of action of methotrexate/Abatacept and may provide new therapeutic targets to prevent autoimmunity in rheumatoid arthritis.


Assuntos
Abatacepte/farmacologia , Antirreumáticos/farmacologia , Artrite Reumatoide/tratamento farmacológico , Metotrexato/farmacologia , Transcriptoma/efeitos dos fármacos , Abatacepte/administração & dosagem , Abatacepte/uso terapêutico , Antirreumáticos/administração & dosagem , Antirreumáticos/uso terapêutico , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Células Sanguíneas/efeitos dos fármacos , Células Sanguíneas/metabolismo , Feminino , Humanos , Masculino , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Pessoa de Meia-Idade
12.
Ann Hematol ; 99(10): 2367-2375, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32816079

RESUMO

This study aimed to define the maximum tolerated dose (MTD) of temozolomide (TMZ) concurrent with radiotherapy (RT) after high-dose methotrexate (HD-MTX) for newly diagnosed primary central nervous system lymphoma (PCNSL). Adult patients with PCNSL were treated according to a response-adapted strategy. HD-MTX (3.5 g/m2) was followed by concomitant RT and escalating TMZ (50-60-75 mg/m2/day, 5 days/week). The total radiation dose was modulated according to the patient's response to HD-MTX. All patients received 30 Gy to the whole brain plus leptomeninges to C2, including the third posterior of the orbital cavity (clinical target volume 2; CTV2), plus 6, 10, or 16 Gy to the primary site, including the residual mass (CTV1), if a complete response (CR), partial response (PR)/stable disease (SD), or progressive disease (PD) was observed, respectively. Acute toxicities were graded according to the RTOG-EORTC criteria. Dose-limiting toxicity (DLT) was defined as grade 4 hematological toxicity or grade 3-4 hepatic toxicity, although 75 mg/m2/day was the maximum dose regardless of DLT. Neurocognitive function was evaluated using the Mini-Mental State Examination. Three patients were enrolled at each TMZ dose level (total = 9 patients). Twelve lesions were treated. Six patients received 2 cycles of HD-MTX, while 3 received only 1 cycle because of hepatic or renal toxicity. All patients completed chemoradiotherapy without interruptions. No DLT events were recorded. TMZ appears to be tolerable at a dose of 75 mg/m2/day when administered concomitantly with radiotherapy and after HD-MTX.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/terapia , Quimiorradioterapia , Irradiação Craniana , Linfoma não Hodgkin/terapia , Temozolomida/uso terapêutico , Adolescente , Adulto , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos Alquilantes/efeitos adversos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Quimioterapia Adjuvante , Transtornos Cognitivos/induzido quimicamente , Quimioterapia de Consolidação , Feminino , Doenças Hematológicas/induzido quimicamente , Humanos , Estimativa de Kaplan-Meier , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/patologia , Masculino , Dose Máxima Tolerável , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Neoplasia Residual , Intervalo Livre de Progressão , Estudos Prospectivos , Temozolomida/efeitos adversos , Adulto Jovem
13.
Dermatol Online J ; 26(6)2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32815688

RESUMO

Calcinosis cutis, although common in systemic sclerosis, has been rarely reported in patients with morphea. We describe four patients with calcinosis cutis arising within morphea plaques, discuss their treatments and outcomes, and review previously published cases. Current management recommendations for concomitant morphea and dystrophic calcinosis cutis are based on limited data and expert opinion, which has primarily focused on reduction of active inflammation and reduction of symptoms related to calcinosis or ulceration. In most cases, no improvement of calcinosis was noted. The use of intralesional corticosteroids to active lesions in conjunction with systemic treatment, including methotrexate when indicated, appear promising treatments to halt progression of the disease. Surgical excision seems to be the most definitive treatment for calcinosis affecting morphea plaques, but the current literature lacks details regarding disease recurrence following operative management.


Assuntos
Calcinose/etiologia , Esclerodermia Localizada/complicações , Dermatopatias/patologia , Pele/patologia , Corticosteroides/uso terapêutico , Calcinose/patologia , Calcinose/cirurgia , Criança , Feminino , Humanos , Injeções Intralesionais , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Esclerodermia Localizada/tratamento farmacológico , Esclerodermia Localizada/patologia , Dermatopatias/terapia
14.
Brasília; s.n; 7 jul. 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1117630

RESUMO

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 17 artigos.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Esteroides/uso terapêutico , Avaliação da Tecnologia Biomédica , Vitamina D/uso terapêutico , Varfarina/uso terapêutico , Ivermectina/uso terapêutico , Ceftriaxona/uso terapêutico , Cloroquina/uso terapêutico , Metotrexato/uso terapêutico , Corticosteroides/uso terapêutico , Azitromicina/uso terapêutico , Ritonavir/uso terapêutico , Oseltamivir/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Lopinavir/uso terapêutico , Infliximab/uso terapêutico , Leflunomida/uso terapêutico , Amoxicilina/uso terapêutico , Hidroxicloroquina/uso terapêutico , Ácido Micofenólico/uso terapêutico
15.
BMJ ; 370: m2288, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32636183

RESUMO

OBJECTIVE: To assess the comparative effectiveness of biological medicines in rheumatoid arthritis in sufficiently similar patient populations, based on the current definitions of key outcomes. DESIGN: Systematic review and network meta-analysis including aggregate results from reanalysed individual patient data. DATA SOURCES: Clinical study reports and aggregate results from reanalyses of individual patient data on key outcomes for rheumatoid arthritis provided by study sponsors for studies conducted up to 2017, and several databases and registries from inception up to February 2017. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials investigating patient relevant outcomes in adults with rheumatoid arthritis treated with biological medicines in combination with methotrexate after methotrexate failure for at least 24 weeks. RESULTS: 45 eligible trials were identified. Combining data from clinical study reports and aggregate results from reanalyses of individual patient data allowed extensive analyses yielding sufficiently similar populations and homogeneous study results for network meta-analyses, including up to 35 studies on eight biological medicines combined with methotrexate. These analyses showed few statistically significant differences between the combination treatments. For example, anakinra showed less benefit than almost all the other seven biological medicines regarding clinical remission or low disease activity (clinical disease activity index ≤2.8 or ≤10, respectively) and certolizumab pegol showed more harm than the other seven biological medicines regarding serious adverse events or infections. Some outcomes had very wide 95% confidence intervals, potentially implying unidentified differences between the eight biological medicines, but wide 95% confidence intervals were less prominent for low disease activity, serious adverse events, and infections. Owing to a lack of head-to-head trials, results were mainly based on indirect comparisons with a limited number of studies, and recently approved Janus kinase inhibitors could not be included. CONCLUSIONS: For patients with rheumatoid arthritis after methotrexate failure, only minor differences in benefits and harms were seen between biological medicines in combination with methotrexate. However, the analysis was hampered by a lack of long term direct comparisons. The substantial information gain achieved by the reanalysis of individual patient data calls for the routine availability of individual patient data.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Adulto , Progressão da Doença , Quimioterapia Combinada , Estudos de Equivalência como Asunto , Feminino , Humanos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Indução de Remissão , Falha de Tratamento
16.
FP Essent ; 494: 11-17, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32640149

RESUMO

Rheumatoid arthritis (RA) is the most common autoimmune inflammatory arthritis, and is seen more commonly in women, smokers, and individuals with a family history of RA. It should be considered if unexplained pain and swelling in the metacarpophalangeal and/or metatarsophalangeal joints and morning stiffness of fingers lasting for longer than 30 minutes are present. RA may be present in the lungs, skin, and eyes. It is associated with an increased risk of cardiovascular death independent of other risk factors. Disease activity should be monitored using a validated scale, such as the Disease Activity Score 28 (DAS28), among others. Earlier management to achieve remission or decrease disease activity is associated with less joint damage, better quality of life, and improved survival rates. Methotrexate with consideration of low-dose glucocorticoids is considered first-line therapy for RA. Other disease-modifying antirheumatic drugs, including immunobiologics, may be used for patients who do not benefit from methotrexate. Before undergoing treatment, patients should be screened for tuberculosis and hepatitis B and C infection. Drug dosages may be tapered in patients with remission or decreased disease activity, but drugs should not be discontinued.


Assuntos
Antirreumáticos , Artrite Reumatoide , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Metotrexato/uso terapêutico , Qualidade de Vida , Índice de Gravidade de Doença
17.
Bull Cancer ; 107(5S): eS8-eS15, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32620213

RESUMO

BACKGROUND: Neoadjuvant cisplatin-based chemotherapy (NAC) is the standard of care in localized muscle-invasive bladder cancer (MIBC). However, 60-70% of patients have residual tumor after NAC. Based on the overall response rate observed in the metastatic setting, ddMVAC is the most commonly used NAC regimen in Europe. The emergence of immune checkpoint inhibitor (ICI) in the metastatic setting raises the question if the combination of chemo plus ICI could increase the pCR rate. METHODS/DESIGN: NEMIO is a French open-label randomized phase I/II trial assessing in the neoadjuvant setting the combination of ddMVAC plus durvalumab alone or with tremelimumab: 4 cycles of ddMVAC/2 weeks + 2 cycles of Durvalumab +/- Tremelimumab/4 weeks. Cystectomy is performed 4-8 weeks after the last dose of ddMVAC. Six pts will be included in each arm in a safety run-in cohort to evaluate the toxicity rate. Each arm will be expanded to a maximum of 60 pts. The primary endpoint of the safety run-in phase will be the rate of grade 3/4 treatment-related adverse events G3/4 TRAE. The primary endpoint of the phase II will be the pathological response rate and G 3/4 TRAE. Exploratory endpoints will include biomarkers of response and resistance to the combo. A total of 120 patients will be included in 15 French centers and we expect the recruitment to be completed in 2021. DISCUSSION: NEMIO trial will assess for the first time the tolerance and the efficacy of ddMVAC regimen associated with checkpoints inhibitors as neoadjuvant treatment in localized MIBC. NCT number: NCT03549715. Registered on June 8, 2018.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células de Transição/tratamento farmacológico , Ensaios Clínicos Fase II como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/patologia , Cisplatino/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Metotrexato/uso terapêutico , Terapia Neoadjuvante , Invasividade Neoplásica , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia , Vimblastina/uso terapêutico
18.
Medicine (Baltimore) ; 99(28): e20966, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664100

RESUMO

To investigate the effectiveness of dual filtration plasmapheresis (DFPP), a novel blood purification treatment, as a rapid and sustained disease-modifying therapy for active refractory rheumatoid arthritis (RA).A retrospective cohort study had been conducted. One hundred fifty three patients aged 18 years or older with active refractory RA were treated with DFPP combined with infliximab (IFX), IFX, or glucocorticoid (GC), all the above treatments were combined with methotrexate (MTX).Baseline characteristic of the 153 patients (DFPP: n = 53; IFX: n = 51; GC: n = 49) were similar across groups. The remission rate of CDAI (SDAI) in the DFPP treatment group was significantly higher than that of the IFX and GC group after 3 months of treatment. The remission rate of DFPP treatment group was above 50%, while in IFX and GC group, the rate of CDAI (SDAI) remission was 41.2% (37.3%) and 22.4% (14.2%) after 3 months of treatment.A combination of DFPP and biological agents can quickly induce remission or low disease activity of active refractory RA.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/terapia , Infliximab/uso terapêutico , Metotrexato/uso terapêutico , Plasmaferese/métodos , Adulto , Idoso , Estudos de Coortes , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
19.
Medicine (Baltimore) ; 99(27): e20824, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629668

RESUMO

INTRODUCTION: Glucocorticoids (GCs), especially low-dose GCs, are commonly prescribed for rheumatoid arthritis (RA), although the risk/benefit ratio is controversial. A randomized, double-blind clinical trial was performed to evaluate the efficacy and safety of low-dose oral GCs combined with methotrexate (MTX) and hydroxychloroquine (HCQ) in early RA (ERA). METHODS: Eighty untreated ERA patients were randomized into the trial (GCs + MTX + HCQ) and control (placebo + MTX + HCQ) groups, for 1-year treatment. Therapeutic evaluation indices were American College of Rheumatology (ACR) 20 of ACR, disease activity score (DAS) 28- erythrocyte sedimentation rate (ESR), visual analog scale scores, joint function, health assessment questionnaire-disability index score, morning stiffness duration, C-reaction protein and ESR. The clinical indicators were evaluated pre-treatment and at 1st, 3th, 6th and 12th month of treatment. The MRI data of single joint (ie, the most swollen joint) for each patient were acquired with a revised OMERACT RAMRIS Scoring System before and after treatment. The correlation analysis was adopted to confirm whether the efficacy of GC treatment is related to the time of RA onset. The side effects (eg, gastrointestinal reactions, liver dysfunction, upper respiratory tract infection, leukocyte reduction) were also monitored. RESULTS: At 1st month, 55% and 20% cases in the experimental and control groups achieved ACR20 response, respectively, indicating a significant difference (χ = 16.157, P < .001). This trend continued until 6th month. At 12th month, the number of patients achieved ACR20 response was similar in both groups. At 1st to 6th month, DAS28- ESR scores in the experimental group were significantly lower than control values (all p < .05). The experimental group showed improved inflammation, quality of life and radiological symptoms. Bone erosion remained unchanged in the experimental group, while worsening in control group. Correlation coefficients between RA duration and DAS28-ESR score were 0.496, 0.464, 0.509, and 0.550 at 1st, 3th, 6th, and 12th month, respectively. No differences were found in adverse events between the 2 groups. CONCLUSIONS: Low-dose GCs combined with MTX and HCQ significantly achieves disease remission indexed by ACR20 and DAS28-ESR, and improves clinical and radiological outcomes in ERA patients at the early stage, with superiority over placebo + MTX + HCQ, without enhancing adverse reactions.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Glucocorticoides/uso terapêutico , Hidroxicloroquina/uso terapêutico , Metotrexato/uso terapêutico , Adulto , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Sedimentação Sanguínea , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Qualidade de Vida , Índice de Gravidade de Doença
20.
PLoS One ; 15(7): e0235637, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32628710

RESUMO

BACKGROUND: The high risk of cardiovascular disease is well recognized in rheumatoid arthritis. Type 2 diabetes also attributes to this increase in risk. Rheumatoid arthritis is a chronic inflammatory condition, which aggravates insulin resistance, placing the patients at a higher risk of type 2 diabetes and subsequent cardiovascular outcomes. Methotrexate treatment, as a gold standard anti-inflammatory drug in the treatment of rheumatoid arthritis has shown beneficial effects on cardiovascular health. However, its impact on type 2 diabetes is still unknown. OBJECTIVE: To assess the strength of the association between exposure to methotrexate and the rate of development of type 2 diabetes in rheumatoid arthritis patients. METHODS: All rheumatoid arthritis studies reporting the use of methotrexate as an exposure and type 2 diabetes as an outcome were searched until March 2020 using MEDLINE, Cochrane and Scopus databases. Studies were included if the diagnosis of rheumatoid arthritis was made according to current guidelines or by a rheumatologist, and if there was information about methotrexate exposure and the type 2 diabetes outcome. The author and an independent assessor evaluated the articles for eligibility. Meta-analyses combined relative risk estimates from each study where raw counts were available. RESULTS: Sixteen studies reporting sufficient data for inclusion in the meta-analyses were identified. Methotrexate showed a promising effect on the risk of type 2 diabetes as this risk decreased in rheumatoid arthritis patients using methotrexate (Relative risk 0.48, 95% CI 0.16, 1.43). CONCLUSION: Rheumatoid arthritis patients on methotrexate treatment had a lower risk of developing type 2 diabetes compared to rheumatoid arthritis patients not exposed to methotrexate. This finding highlights the need for future, randomized control trials to confirm the beneficial effect of methotrexate on type 2 diabetes in the rheumatoid arthritis population.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Diabetes Mellitus Tipo 2/diagnóstico , Metotrexato/uso terapêutico , Fatores Etários , Antirreumáticos/efeitos adversos , Artrite Reumatoide/patologia , Diabetes Mellitus Tipo 2/etiologia , Humanos , Metotrexato/efeitos adversos , Risco , Índice de Gravidade de Doença
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