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1.
J Int Med Res ; 49(6): 3000605211022510, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34139868

RESUMO

In rare cases, clinical inhibitors of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) can induce symptoms of lupus erythematosus (drug-induced lupus, DIL), but this adverse response usually resolves rapidly upon drug withdrawal. We report the case of a 25-year-old Asian woman with rheumatoid arthritis exhibiting severe prolonged DIL even after the termination of TNF-α inhibitor treatment. The patient had been treated intermittently using Traditional Chinese Medicine for 11 years, but this therapy failed to effectively control her clinical symptoms. Subsequently, methotrexate and hydroxychloroquine were prescribed, but a reduced white blood cell count was detected. Finally, the TNF-α inhibitor Anbainuo was prescribed. However, after 2 months of treatment, the patient exhibited elevated serum creatinine, anti-double-stranded DNA (+++), anti-nuclear antibody (1:1000), and urine protein (+++) accompanied by buccal erythema, hair loss, and hand shaking, consistent with Anbainuo-induced lupus, lupus nephritis, and lupus encephalopathy. Moreover, her serum creatinine level remained high after Anbainuo withdrawal and prolonged steroid and immunosuppressive therapy. Careful and sustained monitoring for adverse reactions to Anbainuo (and other TNF-α inhibitors) is recommended.


Assuntos
Antirreumáticos , Artrite Reumatoide , Lúpus Eritematoso Sistêmico , Adulto , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Lúpus Eritematoso Sistêmico/induzido quimicamente , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Metotrexato/uso terapêutico , Receptores Tipo II do Fator de Necrose Tumoral/uso terapêutico , Proteínas Recombinantes de Fusão , Fator de Necrose Tumoral alfa
2.
Medicine (Baltimore) ; 100(24): e26350, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34128886

RESUMO

BACKGROUND: To evaluate the efficacy of fusion proteins biologics (Etanercept (ETN), Anakinra (ANA), and Abatacept) combinations in the treatment of rheumatoid arthritis (RA) using network meta-analysis to rank those according to their performance medicines. The performance of these processes is ranked according to the results of the analysis and an explanatory study of the possible results is carried out. METHODS: Multiple databases including PubMed, EMBASE, and Cochrane Library were used to identify applicable articles and collect relevant data to analyze using STATA (14.0) software. The literature included in this study was divided into a combination of a placebo, methotrexate (MTX), and an observation group (1 of the 3 drugs). The last search date was December 12, 2019. RESULTS: A total of 19 eligible randomized controlled trials of fusion proteins biologics were identified, a total of 1109 papers were included, and the results showed that the ETN + MTX had the highest probability of being the most clinically efficacious intervention, with a surface under the cumulative ranking curve of 91.6, was significantly superior (P < .05). Patients who had received ETN or ETN + MTX or ANA had effective compared with patients who had received placebo (95% CI 1.28%-8.47%; 1.92%-19.18%; 1.06%-10.45%). CONCLUSIONS: 1. The combination of ETN and MTX had the highest probability of optimal treatment compared to other drugs and 2. ENT, ENT + MTX, and ANA were effective in the treatment of RA compared to placebo.


Assuntos
Abatacepte/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Fatores Biológicos/uso terapêutico , Etanercepte/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Quimioterapia Combinada , Humanos , Metotrexato/uso terapêutico , Metanálise em Rede
3.
Arthritis Res Ther ; 23(1): 154, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34074349

RESUMO

OBJECTIVE: To estimate the relationship between serum TNFα, IL-6, and serum CZP levels and the clinical response to CZP in RA patients in the TSUBAME study. METHODS: One hundred patients with RA who received CZP were enrolled and multiple clinical parameters, serum TNFα, IL-6, and CZP levels, were assessed at 0, 24, and 48 h and 12 weeks after first administration of CZP. RESULTS: The CZP therapy significantly improved the DAS28(ESR) at 12 weeks. Serum TNFα and IL-6 levels significantly decreased from baseline at 24 h after the first administration of CZP. Serum TNFα levels at baseline were not related to clinical parameters at baseline and improvement in DAS28(ESR) at week 12 of the CZP therapy. However, serum levels of CZP at 24 h were strongly and negatively correlated with TNFα levels at 24 h, which were negatively correlated with improved rate in DAS28(ESR) at week 12. Only serum levels of TNFα, but not IL-6, at 24 h had a negative correlation with achievement of DAS28(ESR)<2.6 at week 12 by the multivariate analysis (odds ratio 0.01, 95% confidence interval 0.04e-2-0.22, p < 0.01). A receiver operating characteristic analysis was conducted to estimate the achievement of DAS28(ESR)<2.6 at week 12 after the CZP therapy and cut-off value of 0.76 pg/ml for serum levels of TNFα at 24 h was yielded (area under the curve=0.75). DAS28(ESR)<2.6 was achieved at week 12 significantly more patients with lower serum TNF levels (≦0.76 pg/ml) at 24 h than those with higher TNF levels. CONCLUSIONS: CZP was highly effective in RA patients who had low serum TNFα levels at 24 h after the initial administration of CZP. Therefore, we propose that serum TNFα levels at 24 h could serve as a biomarker predicting effectiveness to CZP at week 12 in patients with RA. TRIAL REGISTRATION: Clinical trial registration number: UMIN ID:000022831.


Assuntos
Antirreumáticos , Artrite Reumatoide , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Certolizumab Pegol/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Humanos , Metotrexato/uso terapêutico , Resultado do Tratamento , Fator de Necrose Tumoral alfa
4.
Medicine (Baltimore) ; 100(19): e25684, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34106593

RESUMO

OBJECTIVE: There is no review or meta-analysis to compare the efficacy and safety of methotrexate plus anti-vascular endothelial growth factor (anti-VEGF) therapy in patients with diabetic macular edema (DME). It is worthy to critically review the evidence of the assessment of combined therapies to inform clinical practice. Therefore, the purpose of this study was to compare the efficacy and safety of methotrexate plus anti-VEGF therapy in the treatment of DME and to provide evidence for clinical practice. METHODS: The electronic databases of EMBASE, PubMed, Cochrane Library, and Web of Science were searched from the inception to April 2021 using the following key terms: "diabetic macular edema," "methotrexate," and "anti-vascular endothelial growth factor," for all relevant studies. Additionally, the reference lists from published original articles and relevant reviews were assessed to identify more relevant studies. Only English publications were included. Data were extracted by review of each study for population, mean age, gender, follow-up duration, study design, publishing date, characteristics, and outcomes assessment. The present study was performed using Review Manager (RevMan Version 5.3, The Cochrane Collaboration, Copenhagen, Denmark). RESULTS: We hypothesized that combined therapies would provide better therapeutic benefits compared to single method. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/APD6 V.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antirreumáticos/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Edema Macular/tratamento farmacológico , Metotrexato/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Quimioterapia Combinada , Humanos , Injeções Intravítreas , Edema Macular/etiologia
5.
Mayo Clin Proc ; 96(6): 1530-1545, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34088416

RESUMO

Giant cell arteritis (GCA) is the most common primary systemic vasculitis in adults 50 years or older. Expanded use of advanced arterial imaging has assisted both in the diagnosis of GCA and recognition of disease subsets. Although glucocorticoids have been the mainstay of treatment for almost 7 decades, new therapeutic options have emerged. This review aims to provide the clinician with a pragmatic approach to evaluating and managing patients with GCA while also addressing recent diagnostic and therapeutic developments.


Assuntos
Arterite de Células Gigantes/diagnóstico , Anticorpos Monoclonais Humanizados/uso terapêutico , Arterite de Células Gigantes/diagnóstico por imagem , Arterite de Células Gigantes/tratamento farmacológico , Glucocorticoides/uso terapêutico , Humanos , Metotrexato/uso terapêutico , Indução de Remissão/métodos
6.
Pediatr Surg Int ; 37(8): 1049-1059, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33963920

RESUMO

PURPOSE: Complete upfront resection of pediatric gastrointestinal lymphomas is recommended over biopsy whenever feasible, but either approach may have adverse sequelae. We sought to compare gastrointestinal and oncological outcomes of pediatric gastrointestinal lymphomas who underwent attempted upfront resection or biopsy of the presenting bowel mass. METHODS: We retrospectively reviewed charts of children with gastrointestinal lymphomas treated on LMB89 and LMB96 protocols from 2000 to 2019 who underwent upfront gastrointestinal surgery, and compared resection and biopsy groups. RESULTS: Of 33 children with abdominal lymphomas, 20 had upfront gastrointestinal surgery-10 each had resection or biopsy. Patients with attempted upfront resections had fewer postoperative gastrointestinal complications compared to biopsies (10% vs. 60%, p = 0.057), but longer time to chemotherapy initiation (median 11.5 vs. 4.5 days, p < 0.001). Three resection patients were surgically down-staged. Second surgeries were required in 30% and 40% of resected and biopsied patients, respectively, at median 4.6 months. Survival was similar in both groups, but better in patients on LMB96 protocol and stage II/III disease. CONCLUSIONS: Children with upfront attempted resection had low rates of surgical down-staging, greater delay in chemotherapy initiation, but fewer gastrointestinal complications and subsequent surgeries than biopsies. Survival was similar regardless of upfront surgery, likely reflecting beneficial effects of newer protocols.


Assuntos
Biópsia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Neoplasias do Íleo/cirurgia , Linfoma/cirurgia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Ciclofosfamida/uso terapêutico , Citarabina/uso terapêutico , Feminino , Humanos , Neoplasias do Íleo/tratamento farmacológico , Neoplasias do Íleo/patologia , Lactente , Linfoma/tratamento farmacológico , Linfoma/patologia , Masculino , Metotrexato/uso terapêutico , Estudos Retrospectivos
7.
Transplant Cell Ther ; 27(5): 429.e1-429.e7, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33965186

RESUMO

Severe aplastic anemia (SAA) is a serious bone marrow failure disorder that is often cured with hematopoietic stem cell transplantation (HSCT). The absence of a matched related donor is common, however, and thus novel approaches are needed to safely expand the donor pool to include alternative donors, especially haploidentical related donors, for patients with SAA. This study aimed to explore a novel approach to HSCT for patients with SAA without an available HLA-identical sibling or a matched unrelated donor, termed haploidentical peripheral blood stem cell transplantation (haplo-PBSCT), using a conditioning regimen comprising cyclophosphamide, busulfan, and fludarabine (CBF) and a graft-versus-host disease (GVHD) prophylaxis regimen with post-transplantation cyclophosphamide (PTCy), low-dose methotrexate (LD-MTX), and calcineurin inhibitors. This prospectively designed nonrandomized study included 29 patients with SAA who underwent haplo-PBSCT between November 2017 and May 2020. The median patient age was 17 years (range, 14 to 30 years), and the median time to neutrophil recovery was 13 days (range, 13 to 15 days). There was 1 primary graft failure (GF) in the group receiving PTCy at a dose of 50 mg/kg and no GFs in the group receiving PTCy at a dose of 100 mg/kg. The median duration of follow-up was 736 days (95% confidence interval, 512 to 879 days). The estimated 1-year overall survival and disease-free survival were 91.7 ± 5.7% and 89.7 ± 5.7%, respectively. Only 1 of the 27 patients developed grade II acute GVHD. Four patients developed limited and mild chronic GVHD, involving only the skin or/and oral mucosa. Haplo-PBSCT following CBF and followed by PTCy and LD-MTX represents a novel approach for safely expanding the donor pool to include alternative donors for young patients with SAA.


Assuntos
Anemia Aplástica , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco de Sangue Periférico , Adolescente , Adulto , Anemia Aplástica/terapia , Ciclofosfamida/uso terapêutico , Humanos , Metotrexato/uso terapêutico , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Adulto Jovem
8.
Ann Hematol ; 100(7): 1837-1847, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33948721

RESUMO

Despite the widespread use of rabbit anti-thymocyte globulin (ATG) to prevent acute and chronic graft-versus-host disease (aGVHD, cGVHD) after allogeneic hematopoietic cell transplantation (allo-HCT), convincing evidence about an optimal dose is lacking. We retrospectively evaluated the clinical impact of two different ATG doses (5 vs 6-7.5 mg/kg) in 395 adult patients undergoing HSCT from matched unrelated donors (MUD) at 3 Italian centers. Cumulative incidence of aGVHD and moderate-severe cGVHD did not differ in the 2 groups. We observed a trend toward prolonged overall survival (OS) and disease-free survival (DFS) with lower ATG dose (5-year OS and DFS 56.6% vs. 46.3%, p=0.052, and 46.8% vs. 38.6%, p=0.051, respectively) and no differences in relapse incidence and non-relapse mortality. However, a significantly increased infection-related mortality (IRM) was observed in patients who received a higher ATG dose (16.7% vs. 8.8% in the lower ATG group, p=0.019). Besides, graft and relapse-free survival (GRFS) was superior in the lower ATG group (5-year GRFS 43.1% vs. 32.4%, p=0.014). The negative impact of higher ATG dose on IRM and GRFS was confirmed by multivariate analysis. Our results suggest that ATG doses higher than 5 mg/kg are not required for MUD allo-HCT and seem associated with worse outcomes.


Assuntos
Soro Antilinfocitário/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adulto , Aloenxertos , Soro Antilinfocitário/administração & dosagem , Soro Antilinfocitário/efeitos adversos , Ciclosporina/uso terapêutico , Intervalo Livre de Doença , Relação Dose-Resposta Imunológica , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/terapia , Histocompatibilidade , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Incidência , Infecções/etiologia , Infecções/mortalidade , Estimativa de Kaplan-Meier , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Modelos de Riscos Proporcionais , Recidiva , Estudos Retrospectivos , Linfócitos T/imunologia , Doadores não Relacionados
9.
Chin Med J (Engl) ; 134(12): 1457-1464, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34039871

RESUMO

BACKGROUND: Clinical observational studies revealed that 99Tc-methylene diphosphonate (99Tc-MDP) could reduce joint pain and swollenness in rheumatoid arthritis (RA) patients. This multicenter, randomized, double-blind, double-dummy study aimed to evaluate the effects of 99Tc-MDP plus methotrexate (MTX) vs. MTX alone or 99Tc-MDP alone on disease activity and structural damage in MTX-naïve Chinese patients with moderate to severe RA. METHODS: Eligible patients with moderate to severely active RA were randomized to receive 99Tc-MDP plus MTX (n = 59) vs. MTX (n = 59) alone or 99Tc-MDP (n = 59) alone for 48 weeks from six study sites across four provinces in China. The primary outcomes were the American College of Rheumatology 20% improvement (ACR20) response rates at week 24 and changes in modified total Sharp score at week 48. RESULTS: At week 24, the proportion of participants achieving ACR20 was significantly higher in the MTX + 99Tc-MDP combination group (69.5%) than that in the MTX group (50.8%) or 99Tc-MDP group (47.5%) (P = 0.03 for MTX + 99Tc-MDP vs. MTX, and MTX + 99Tc-MDP vs.99Tc-MDP, respectively). The participants in the MTX + 99Tc-MDP group and the 99Tc-MDP group had significantly less important radiographic progression than the participants in the MTX group over the 48 weeks (MTX + 99Tc-MDP vs. MTX: P = 0.03, 99Tc-MDP vs. MTX: P = 0.03, respectively). There was no significant difference in terms of adverse events (AEs) among the groups. No serious AEs were observed. CONCLUSIONS: This study demonstrated that the combination of 99Tc-MDP with MTX inhibited structural damage and improved disease activity in RA patients compared with MTX and 99Tc-MDP monotherapies, without increasing the rate of AEs. Additional clinical studies of 99Tc-MDP therapy in patients with RA are warranted. TRIAL REGISTRATION: Chictr.org, ChiCTR-IPR-14005684; http://www.chictr.org.cn/showproj.aspx?proj=10088.


Assuntos
Antirreumáticos , Artrite Reumatoide , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , China , Difosfonatos , Método Duplo-Cego , Quimioterapia Combinada , Humanos , Metotrexato/uso terapêutico , Tecnécio/uso terapêutico , Resultado do Tratamento
10.
Acta Biomed ; 92(2): e2021050, 2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-33988175

RESUMO

A single case of ultrasonographic-guided local injection of methotrexate for managing scar pregnancy is reported. The outcome was successful and had no side effects. The case was reported to increase the evidence supporting this type of management.


Assuntos
Abortivos não Esteroides , Gravidez Ectópica , Cesárea , Cicatriz/tratamento farmacológico , Feminino , Humanos , Metotrexato/uso terapêutico , Gravidez , Gravidez Ectópica/diagnóstico por imagem , Gravidez Ectópica/tratamento farmacológico , Resultado do Tratamento
11.
Medicine (Baltimore) ; 100(20): e25534, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011024

RESUMO

BACKGROUND: Osteosarcoma is a primary form of malignant bone tumor. It is commonly prevalent among children. Treating osteosarcoma with chemotherapy has had limited clinical outcomes due to side effects and the formation of drug resistance. Presently, a mixture of doxorubicin, cisplatin, ifosfamide, epirubicin methrotrexate, and other supplementary medications are used in osteosarcoma chemotherapy. Therefore, this study aims to investigate the clinical therapeutic effects of combining methotrexate with other chemotherapeutic agents to treat osteosarcoma in children. METHODS: The search of several electronic databases will lead to source related published studies. The electronic databases include both English (PubMed, EMBASE, Web of Science, and the Cochrane Library) and Chinese (China National Knowledge Infrastructure, WanFang, and China Biomedical Database) databases. All studies published from inception to November 19, 2020 are searched. Study selection, extraction of data, and evaluation of the bias risk in included studies are carried out by two authors independently. The software, RevMan 5.3, is used to analyze the data. RESULTS: This study provides evidence of substantial quality for the clinical therapeutic effects of methotrexate combined with other chemotherapeutic agents for treating osteosarcoma in children. CONCLUSION: The results of this study provide conclusive evidence with regards to the clinical application of methotrexate combined with other chemotherapeutic agents for treating osteosarcoma in children. ETHICS AND DISSEMINATION: Since this study will use published data, ethical approval is not required. SYSTEMATIC REVIEW REGISTRATION NUMBER: This protocol has been registered on INPLASY202110024.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/terapia , Metotrexato/uso terapêutico , Recidiva Local de Neoplasia/epidemiologia , Osteossarcoma/terapia , Adolescente , Neoplasias Ósseas/mortalidade , Quimioterapia Adjuvante/métodos , Criança , Intervalo Livre de Doença , Humanos , Metanálise como Assunto , Recidiva Local de Neoplasia/prevenção & controle , Osteossarcoma/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida , Revisões Sistemáticas como Assunto , Fatores de Tempo
12.
J Pharm Biomed Anal ; 201: 114124, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34000579

RESUMO

We developed and validated a quantification method for methotrexate (MTX) polyglutamates (MTX-PGs, MTX-PG1 to MTX-PG5) by liquid chromatography-tandem mass spectrometry using stable isotope-labeled internal standards and applied to 196 clinical samples collected from pediatric acute lymphoblastic leukemia patients treated with MTX. MTX-PGs levels and their proportions (%) in sum of all MTX-PGs (MTXSum) were evaluated in relation to TPMT, NUDT15, and MTHFR genotypes. For the developed method, linearity ranges 1-500 nmol/L, bias for accuracy 0.3-13.5 %, coefficient of variation for within- and between-run imprecision of 3.2-9.5% and 1.5-12.0%, respectively. Recoveries achieved were 74.2-105.8 %. There was no significant carryover. The median level of the MTXSum for 196 clinical samples was 129.4 nmol/L (interquartile range 28.1-241.2). MTX dose and MTX-PGs were associated (P < 0.05) and among five MTX-PGs, MTX-PG3 was the predominant form (median 41.7 %). The MTX-PG3 level was significantly higher in patients with TPMT *1/*3C than in patients with wild type and MTX-PG3% was significantly higher and MTX-PG5% was significantly lower in NUDT15 intermediate metabolizers than normal or indeterminate phenotypes (P < 0.05). This validated MTX-PGs quantification method can facilitate a better understanding of MTX metabolism and therapeutic drug monitoring for MTX treatment.


Assuntos
Metotrexato , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Humanos , Metotrexato/análogos & derivados , Metotrexato/uso terapêutico , Ácido Poliglutâmico/análogos & derivados , Polimorfismo Genético , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética
13.
Clin Dermatol ; 39(1): 76-83, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33972056

RESUMO

As of July 9, 2020, there were more than 12 million confirmed cases of coronavirus disease 2019 (COVID-19) across the globe, with more than 550,000 deaths. Many European countries, including Belgium, the United Kingdom, Italy, and Spain, have had the highest numbers of fatalities per capita. This indicates the potential for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus to overwhelm even the most advanced health care systems despite extreme societal interventions. Since its emergence, SARS-CoV-2 has disseminated across the globe, affecting the structure of global societies, infrastructure, and economies. Patients with alopecia are a diverse group who, for various indications, are prescribed a number of antimicrobials and antiandrogen treatments in addition to immunomodulatory therapies such as hydroxychloroquine, oral corticosteroids, and a range of broad immunosuppressants. These drugs are being scrutinized for their capacity to potentially affect SARS-CoV-2 outcomes. We examine these treatments and highlight the critical role that patient registries will play in generating real-world evidence to assess their impact on COVID-19 outcomes.


Assuntos
Alopecia/tratamento farmacológico , COVID-19/tratamento farmacológico , Alopecia/classificação , Antagonistas de Androgênios/uso terapêutico , Antibacterianos/uso terapêutico , Antimaláricos/uso terapêutico , Ciclosporina/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Imunossupressores/uso terapêutico , Inibidores de Janus Quinases/uso terapêutico , Metotrexato/uso terapêutico , Prognóstico , Sistema de Registros , SARS-CoV-2
15.
Am J Hematol ; 96(7): 764-771, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33811794

RESUMO

Central nervous system (CNS) relapse affects 5% of diffuse large B-cell lymphoma (DLBCL) patients and portends a poor prognosis. Prophylactic intravenous high-dose methotrexate (HD-MTX) is frequently employed to reduce this risk, but there is limited evidence supporting this practice. We conducted a multicenter retrospective study to determine the CNS relapse risk with HD-MTX in DLBCL patients aged 18-70 years treated in Alberta, Canada between 2012 and 2019. Provincial guidelines recommended HD-MTX for patients at high-risk of CNS relapse based upon CNS-IPI score, double-hit lymphoma, or testicular involvement. Among 906 patients with median follow-up 35.3 months (range 0.29-105.7), CNS relapse occurred in 1.9% with CNS-IPI 0-1, 4.9% with CNS-IPI 2-3, and 12.2% with CNS-IPI 4-6 (p < .001). HD-MTX was administered to 115/326 (35.3%) high-risk patients, of whom 96 (83.5%) had CNS-IPI score 4-6, 45 (39.1%) had double-hit lymphoma, and four (3.5%) had testicular lymphoma. The median number of HD-MTX doses was two (range 1-3). Central nervous system relapse risk was similar with versus without HD-MTX (11.2% vs. 12.2%, p = .82) and comparable to previous reports of high-risk patients who did not receive CNS prophylaxis (10-12%). In multivariate and propensity score analyses, HD-MTX demonstrated no association with CNS relapse, progression-free survival, or overall survival. This study did not demonstrate a benefit of prophylactic HD-MTX in this high-risk patient population. Further study is required to determine the optimal strategy to prevent CNS relapse in DLBCL.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias do Sistema Nervoso Central/prevenção & controle , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Metotrexato/uso terapêutico , Recidiva Local de Neoplasia/prevenção & controle , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Neoplasias do Sistema Nervoso Central/etiologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Linfoma Difuso de Grandes Células B/etiologia , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
16.
Am J Hematol ; 96(7): 772-780, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33819354

RESUMO

Large granular lymphocytic leukemia (LGLL) is a rare hematological malignancy that arises from cytotoxic T lymphocytes (T-LGLL) in 85% of cases and natural killer (NK) cells in the rest. A significant knowledge gap exists regarding the pathogenesis, treatment choices, and prognostic factors of LGLL. We report a cohort of 319 consecutive LGLL patients who presented to our cancer center between 2001 and 2020. A total of 295 patients with T-LGLL and 24 with chronic NK-cell lymphoproliferative disorder (CLPD-NK) were identified. The median age was 65 years (range, 17-90 years). Eighty-three patients (26.0%) had autoimmune diseases. A total of 119 patients (37.3%) had coexisting malignancies, 66 (20.7%) had solid tumors, and 59 (18.5%) had hematological malignancies. Most coexisting malignancies were diagnosed before the diagnosis of LGLL. Treatment was needed for 57% of patients. Methotrexate (MTX), cyclophosphamide (Cy), and cyclosporine A (CSA) were most used and had similar response rates between 61.5%-74.4%. Cy produced more complete responses (32.3%) compared to MTX and CSA (15.7% and 23.1%, respectively). Thrombocytopenia, splenomegaly, and female gender (after controlling for autoimmune diseases) were associated with decreased response rates to MTX, CSA, or Cy. Autoimmune diseases were associated with increased response rates. Thrombocytopenia was an independent risk factor for worse survival.


Assuntos
Leucemia Linfocítica Granular Grande/diagnóstico , Leucemia Linfocítica Granular Grande/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Ciclofosfamida/uso terapêutico , Ciclosporina/uso terapêutico , Gerenciamento Clínico , Feminino , Humanos , Imunossupressores/uso terapêutico , Leucemia Linfocítica Granular Grande/tratamento farmacológico , Leucemia Linfocítica Granular Grande/epidemiologia , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
17.
Am J Hematol ; 96(7): 823-833, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33864703

RESUMO

The treatment of primary vitreoretinal lymphoma (PVRL) remains controversial regarding the use of local, systemic, or combined treatments. The aim of this study was to analyze the efficacy and toxicity of intravenous high-dose methotrexate (IV HD-MTX) based systemic therapy in a uniformly treated population of PVRL patients. From a nationwide French database, we retrospectively selected 59 patients (median age: 70 years, median Karnofsky Performance Status: 90%) with isolated PVRL at diagnosis who received first-line treatment with HD-MTX between 2011 and 2018. 8/59 patients also received a local treatment. No deaths or premature discontinuations of MTX due to toxicity were reported. A complete response was obtained in 40/57 patients after chemotherapy. Before treatment, IL-10 was elevated in the aqueous humor (AH) or in the vitreous in 89% of patients. After treatment, AH IL-10 was undetectable in 87% of patients with a CR/uCR/PR and detectable in 92% of patients with PD/SD. After a median follow-up of 61 months, 42/59 (71%) patients had relapsed, including 29 isolated ocular relapses as the first relapse and a total of 22 brain relapses. The median overall survival, progression-free survival, ocular-free survival and brain-free survival were 75, 18, 29 and 73 months, respectively. IV HD-MTX based systemic therapy as a first-line treatment for isolated PVRL is feasible, with acceptable toxicity, even in an elderly population. This strategy seems efficient to prevent brain relapse with prolonged overall survival. However, the ocular relapse rate remains high. New approaches are needed to improve local control of this disease, and ocular assessment could be completed by monitoring AH IL-10.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Linfoma Intraocular/tratamento farmacológico , Metotrexato/uso terapêutico , Neoplasias da Retina/tratamento farmacológico , Administração Intravenosa , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Feminino , Humanos , Linfoma Intraocular/diagnóstico , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Retina/diagnóstico , Resultado do Tratamento
18.
J Int Med Res ; 49(4): 300060521999533, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33874776

RESUMO

Primary central nervous system Hodgkin's lymphoma (CNS-HL) is extremely rare. This current case report describes a 60-year-old male patient that presented with numbness of the left lower extremity and worsening headache. After a full range of investigations and a partial resection of the right cerebellum, external ventricular drainage reservoir placement and cranioplasty, he was diagnosed with primary CNS-HL. The patient was treated with 3 g/m2 methotrexate (intravenous [i.v.], once a day, day 1) and 1 g/m2 cytarabine (i.v., every 12 h, days 2 + 3), followed by anti-programmed cell death protein 1 antibodies (200 mg sintilimab, i.v., once a day, day 1, every 3 weeks). After six courses of treatment with intrathecal injections of 50 mg cytarabine (once a day, day 1) and 5 mg dexamethasone (once a day, day 1), there was no residual lesion on cranial magnetic resonance imaging. No significant drug-related adverse events were observed. The patient has been followed up every 3 months and no relapse has occurred.


Assuntos
Neoplasias do Sistema Nervoso Central , Doença de Hodgkin , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sistema Nervoso Central , Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/cirurgia , Citarabina/uso terapêutico , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/cirurgia , Humanos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico
19.
Eur J Intern Med ; 88: 96-103, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33879385

RESUMO

OBJECTIVES: To assess the efficacy and safety of adjuvant therapies in newly diagnosed or relapsing giant cell arteritis (GCA) in terms of relapse rate at week 52 (primary outcome) and to assess the impact of GC tapering regimen on adjuvant effectiveness. METHODS: For this systematic review and meta-analysis, we searched PubMed, EMBASE, CENTRAL, trial registries, from inception to November 2020. We included all randomized controlled trials (RCTs) and controlled prospective studies evaluating adjuvant treatments in GCA, without date or language restriction. Two reviewers independently selected studies, extracted data and assessed risk of bias. Quality of evidence was summarised with GRADE. RESULTS: Of the 680 records identified, 16 studies were included (1,068 participants) evaluating various adjuvant therapies compared to GC only. No study compared adjuvants with each other. Risk of bias was high in 5/7 trials evaluating our primary outcome. Risk of relapse at week 52 was reduced for only the anti-IL6 and IL6-receptor drug class versus the control (RR=0.45, 95%CI 0.30-0.66, I2=38%), particularly tocilizumab (RR=0.38, 95%CI 0.23-0.63, I2=42%) with a moderate quality of evidence. We found no significant interaction according to GC tapering regimen. Our meta-analysis did not show a significant benefit for methotrexate. Except for dapsone, ciclosporine and hydroxychloroquine, other adjuvants did not seem to show increased risk of adverse events. CONCLUSIONS: Tocilizumab seems to reduce the relapse rate in GCA at week 52 but the quality of evidence was moderate. No other molecule has shown efficacy. No significant interaction on relapse rate by GC tapering regimen was found. STUDY REGISTRATION: PROSPERO CRD42020172011.


Assuntos
Arterite de Células Gigantes , Quimioterapia Combinada , Arterite de Células Gigantes/tratamento farmacológico , Glucocorticoides/uso terapêutico , Humanos , Metotrexato/uso terapêutico , Esteroides/uso terapêutico
20.
N Z Med J ; 134(1533): 61-70, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33927424

RESUMO

AIMS: To evaluate the approach to diagnosis and management of caesarean scar pregnancy (CSP) at a regional New Zealand hospital. METHODS: A retrospective case series of ten patients between June 2015 and May 2020. The data review included demographic information, ultrasound findings, human chorionic gonadotropin (HCG) levels, primary and subsequent treatment, outcomes and complications. RESULTS: Nine women were diagnosed with CSP at a gestational age between four and ten weeks. One of these women was treated twice for two separate CSP within the study period. Treatment varied according to clinical presentation, HCG levels, gestational age, ultrasound findings and patient preference. Two thirds of women were successfully treated with primary management, with one third requiring multiple treatment modalities. We report one severe life-threatening haemorrhage and three cases resulting in hysterectomy. We also show a disproportionate number of Maori women presenting with CSP. CONCLUSION: We present a series of ten cases of CSP and demonstrate similar challenges in regional New Zealand to those reported elsewhere. Management is heterogeneous with little guidance from the literature, and primary management was successful in seven out of ten cases. We report a disproportionately high number of cases in Maori women. Our results would support the development of a national register for caesarean scar pregnancy to improve diagnosis and management across New Zealand.


Assuntos
Cesárea/efeitos adversos , Cicatriz/patologia , Gravidez Ectópica/patologia , Gravidez Ectópica/terapia , Dor Abdominal/etiologia , Abortivos não Esteroides/uso terapêutico , Adulto , Cicatriz/etiologia , Dilatação e Curetagem , Feminino , Humanos , Histerectomia , Metotrexato/uso terapêutico , Misoprostol/uso terapêutico , Nova Zelândia , Grupo com Ancestrais Oceânicos , Gravidez , Gravidez Ectópica/diagnóstico por imagem , Gravidez Ectópica/etnologia , Estudos Retrospectivos , Ultrassonografia Pré-Natal , Hemorragia Uterina/etiologia
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