Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 11.188
Filtrar
1.
Surg Clin North Am ; 100(1): 161-173, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31753110

RESUMO

Advanced/metastatic melanoma is an aggressive cancer with a low survival rate. Traditional cytotoxic chemotherapies do not appreciably extend life and systemic cytokine/chemokine administration produces toxic side effects. By harnessing the surveillance and cytotoxic features of the immune system, immunotherapies can provide a durable response and are proved to improve disease outcomes in patients with advanced/metastatic melanoma and other cancers. Close monitoring is necessary, however, to identify and treat immune system-related adverse events before they become life-threatening. Because metastatic lesions can respond differently to immunotherapies, modified response criteria have been developed to assist physicians in tracking patient response to treatment.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Imunoterapia/métodos , Melanoma/terapia , Neoplasias Cutâneas/terapia , Antineoplásicos Imunológicos/imunologia , Humanos , Fatores Imunológicos/imunologia , Fatores Imunológicos/uso terapêutico , Melanoma/imunologia , Neoplasias Cutâneas/imunologia
2.
Adv Exp Med Biol ; 1209: 181-203, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31728871

RESUMO

Autophagy, a highly conserved and multistep lysosomal degradation process, plays a pivotal role in maintaining cellular and physiological homeostasis. Of note, autophagy controls intracellular homeostasis and cell responses to stresses by regulating the self-renewal, maturation, and survival of immune cells. And dysregulation of autophagy in immune cells may contribute to the inflammatory disorders and defect in immune responses against invasive pathogens. Accumulating evidence have indicated that dysregulated autophagy participates in the pathology of immune-related diseases. Therefore, targeting autophagy might represent a promising therapeutic strategy for treatment of immune-related diseases. In this chapter, we focus on discussing the link between autophagy and pathogenesis of immune-related diseases, as well as the dysregulation of autophagy-related signaling pathways, in different diseases. Moreover, we highlight the therapeutic potential of currently used small-molecule modulators of autophagy for treatment of immune-related diseases and illustrate the mechanisms of these small-molecule modulators.


Assuntos
Autofagia , Doenças do Sistema Imunitário , Fatores Imunológicos , Homeostase , Humanos , Doenças do Sistema Imunitário/tratamento farmacológico , Doenças do Sistema Imunitário/fisiopatologia , Fatores Imunológicos/química , Fatores Imunológicos/uso terapêutico , Transdução de Sinais
3.
Medicine (Baltimore) ; 98(44): e17801, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689860

RESUMO

RATIONALE: Anti-glomerular basement membrane (GBM) disease is a T cell-mediated disease that has a poor prognosis with conventional therapy. We tested rituximab as a primary therapy to reduce anti-GBM antibody produced by B cells. PATIENT CONCERNS: A 53-year old woman with complaints of a fever, headache and abdominal discomfort showed renal failure with elevated anti-GBM antibody, and renal biopsy revealed crescentic necrotizing glomerulonephritis with linear immunoglobulin G (IgG) 1 deposition along GBM. DIAGNOSES: The patient's plasma contained autoantibodies against Goodpasture antigen, which is the NC domain of collagen IVα3, and CD4-positive helper T cells were found surrounding crescent glomeruli with the coexistence CD20-positive B cells. INTERVENTIONS: Rituximab with steroid and plasma exchange. OUTCOMES: The levels of autoantibody for Goodpasture antigen were reduced, and the patient was able to temporarily withdraw from hemodialysis. LESSONS: B cell depletion with rituximab is effective as an initial therapy for anti-GBM disease.


Assuntos
Doença Antimembrana Basal Glomerular/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Troca Plasmática/métodos , Rituximab/uso terapêutico , Esteroides/uso terapêutico , Doença Antimembrana Basal Glomerular/sangue , Doença Antimembrana Basal Glomerular/imunologia , Autoanticorpos/sangue , Terapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento
4.
Anticancer Res ; 39(10): 5675-5682, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570466

RESUMO

BACKGROUND/AIM: This study explored the prognostic significance of the neutrophil-to-lymphocyte ratio (NLR) and use of antibiotics in advanced esophageal squamous cell carcinoma (ESCC) patients receiving immune checkpoint inhibitors (ICIs). PATIENTS AND METHODS: Patients were enrolled from two referral centers in Taiwan. Clinical benefit was defined as complete response, partial response, or a stable disease for ≥6 months via Response Evaluation Criteria In Solid Tumors 1.1. Clinicopathological factors' impact on overall survival (OS) and progression-free survival (PFS) was analyzed via Cox proportional hazards model. RESULTS: Forty-nine patients were enrolled. The median PFS and OS were 1.8 and 6.1 months, respectively. The median NLR at baseline was 6.40, and 21 patients received antibiotics. Both high NLR and use of antibiotics were associated with inferior PFS (p=0.028 and p<0.001, respectively) and OS (p<0.001 and p<0.001, respectively) in multivariate analysis. CONCLUSION: High NLR and use of antibiotics were associated with inferior survival in advanced ESCC patients receiving ICIs.


Assuntos
Antibacterianos/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Linfócitos/patologia , Neutrófilos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Linfócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Taiwan
5.
Cancer Immunol Immunother ; 68(12): 1949-1958, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31637474

RESUMO

Diffusing alpha-emitters radiation therapy (DaRT) is the only known method for treating solid tumors with highly destructive alpha radiation. More importantly, as a monotherapy, DaRT has been shown to induce a systemic antitumor immune response following tumor ablation. Here, immunomodulatory strategies to boost the antitumor immune response induced by DaRT, and the response specificity, were investigated in the colon cancer CT26 mouse model. Local treatment prior to DaRT, with the TLR3 agonist poly I:C, was sufficient to inhibit tumor growth relative to poly I:C or DaRT alone. DaRT used in combination with the TLR9 agonist CpG, or with the TLR1/2 agonist XS15 retarded tumor growth and increased tumor-rejection rates, compared to DaRT alone, curing 41% and 20% of the mice, respectively. DaRT in combination with CpG, the Treg inhibitor cyclophosphamide, and the MDSC inhibitor sildenafil, cured 51% of the animals, compared to only 6% and 0% cure when immunomodulation or DaRT was used alone, respectively. Challenge and Winn assays revealed that these high cure rates involved a specific immunological memory against CT26 antigens. We suggest that DaRT acts in synergy with immunomodulation to induce a specific and systemic antitumor immune response. This strategy may serve as a safe and efficient method not only for tumor ablation, but also for in situ vaccination of cancer patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Braquiterapia , Neoplasias do Colo/terapia , Ciclofosfamida/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Neoplasias Experimentais/terapia , Partículas alfa , Animais , Antígenos de Neoplasias/imunologia , Células Cultivadas , Feminino , Humanos , Imunidade , Memória Imunológica , Camundongos , Camundongos Endogâmicos BALB C , Poli I-C/administração & dosagem , Indução de Remissão
6.
Medicine (Baltimore) ; 98(37): e17041, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517824

RESUMO

BACKGROUND: Treatment of lupus nephritis (LN) remains challenging. LN remains the primary source of morbidity and mortality in patients with systemic lupus erythematosus. Chinese patent medicine Bailing capsule is commonly used for the treatment of LN. However, there is no consensus on the difference in clinical efficacy compared with routine treatment. Therefore, we plan to perform a systematic review and meta-analysis to review the clinical efficacy and safety of Bailing capsule for LN. METHODS: Cochrane Central Register of Controlled Trials, PubMed, EMBASE, Chinese National Knowledge Infrastructure, Chinese Biomedical Database, Wanfang database, and VIP information database will be searched from their inception until January 2019. The meta-analysis will be conducted with Review Manager 5.3 software to systematically review the clinical efficacy and safety of Bailing capsule for LN. The primary outcome will include clinical effective rate, and the secondary outcomes will include Systemic Lupus Erythematosus Disease Activity Index, serum creatinine, 24-hour urine protein quantity, complement 3, and adverse effects. RESULTS: This analysis will provide useful information about clinical efficacy and safety of Bailing capsule for LN. CONCLUSIONS: Our study will generate strong evidence of Bailing capsule for patients with LN and provide suggestions for clinical practice.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Metanálise como Assunto , Revisão Sistemática como Assunto , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Fatores Imunológicos/efeitos adversos
7.
Internist (Berl) ; 60(10): 1043-1058, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31501913

RESUMO

Therapeutic regimens using monoclonal antibodies have been implemented in clinical daily practice for various gastroenterological diseases, for therapeutic strategies in gastrointestinal (GI) oncology, and infectious diseases of the gastrointestinal tract. The main indications remain the therapy of chronic inflammatory bowel disease and in GI oncology. A new field has opened for targeted therapy with monoclonal antibodies of recurrent Clostridium difficile infection. In the nomenclature of monoclonal antibodies, the endings of the substances indicate the production or degree of "humanization" of the respective antibodies ("umab": fully human, recombinant antibody; "ximab": chimeric antibody with variable murine domain). For chronic inflammatory bowel disease, monoclonal antibodies has been developed to interfere with molecular targets of the inflammatory cascade in the underlying pathogenesis (tumor necrosis factor­α, interleukin-12 and -23; α4ß7-integrins). The development of targeted therapies in the treatment of GI malignancies, monoclonal antibodies has been developed to interfere with substantial pathways of proliferation and apoptosis as well as neoplastic vascularization and neovascularization (e.g., vascular endothelial growth factor [VEGF] and VEGF receptor antibodies, epidermal growth factor receptor antibodies, HER2/neu antibodies). In the current review, we provide a summary of the current applications of monoclonal antibodies in the therapeutic treatment of gastroenterological diseases.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Gastroenteropatias/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Terapia de Alvo Molecular/métodos , Animais , Anticorpos Monoclonais/farmacologia , Antineoplásicos Imunológicos , Colite Ulcerativa/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Receptores ErbB/efeitos dos fármacos , Gastroenterologia , Humanos , Fatores Imunológicos/farmacologia , Camundongos , Receptores de Fatores de Crescimento do Endotélio Vascular/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular
8.
Expert Rev Clin Pharmacol ; 12(10): 981-989, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31498683

RESUMO

Introduction: Psoriasis is affected by many environmental factors, including infections and antibiotics. However, the relationship between antibiotics and psoriasis is inadequately studied. Some antibiotics were listed as triggering factors; others showed benefit for psoriasis control. The aim of this article is to review current evidence that may help identify appropriate antibiotics for patients with psoriasis. Areas covered: The PubMed, Embase, Clinicalkey databases, and google scholar were searched for relevant articles published up to May 2019. Literature regarding antibiotics and psoriasis were included. Six randomized controlled trials and four controlled or cohort studies were identified in 13 kinds of antibiotics. Expert opinion: Macrolides and rifampin showed decrease of psoriasis area and severity index score in plaque-type psoriasis, while penicillin revealed no statistically significant improvement in guttate psoriasis. Previously tetracyclines were considered as triggering factors, but data were found only in cases or retrospective studies. Mechanisms were thought to be related to immunomodulation rather than bacteria inhibition. Research gap in the influence of genetic susceptibility, the impact on microbiota, and the mode of actions remain to be investigated.


Assuntos
Antibacterianos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Psoríase/tratamento farmacológico , Animais , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Humanos , Fatores Imunológicos/farmacologia , Macrolídeos/efeitos adversos , Macrolídeos/farmacologia , Macrolídeos/uso terapêutico , Psoríase/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Rifampina/efeitos adversos , Rifampina/farmacologia , Rifampina/uso terapêutico , Índice de Gravidade de Doença
9.
Cochrane Database Syst Rev ; 8: CD012893, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31476018

RESUMO

BACKGROUND: Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract, and immune response modulation is the main treatment strategy to induce remission in active CD. Certolizumab pegol (CZP) is a tumor necrosis factor-alfa (TNF-α) inhibitor which regulates impaired immune response. OBJECTIVES: The primary objectives were to evaluate the efficacy and safety of CZP for the induction of remission in CD. SEARCH METHODS: We searched MEDLINE, Embase, CENTRAL, the Cochrane IBD group specialized register, trials registers and other sources from inception to 28 January 2019. Moreover, we contacted the pharmaceutical company that manufactures CZP. SELECTION CRITERIA: We included randomized controlled trials comparing CZP with placebo or no treatment in active CD patients. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. The main outcomes selected for GRADE analysis were clinical remission at week 8 (Crohn's Disease Activity Index [CDAI] ≤150), clinical response at week 8 (CDAI reduction ≥ 100 or clinical remission), and serious adverse events. The Mantel-Haenszel random-effects method was applied for the statistical analyses. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). MAIN RESULTS: Four studies involving 1485 participants with moderate to severe CD met the inclusion criteria and were used in the meta-analyses. All studies included active CD patients with CDAI ranging from 220 to 450. Most patients were adults over 18 years of age. One study was identified as high risk of bias due to a non-identical placebo while the other studies were judged to be at low risk of bias.CZP (100 mg to 400 mg every 2 to 4 weeks) was shown to be superior to placebo for achieving clinical remission at week 8 (RR 1.36, 95% CI 1.11 to 1.66; moderate certainty evidence). The raw numbers of participants achieving clinical remission at week 8 were 26.9% (225/835) and 19.8% (129/650) in the CZP and the placebo groups, respectively.CZP was shown to be superior to placebo for achieving clinical response at week 8 (RR 1.29, 95% CI 1.09 to 1.53; moderate certainty evidence). In raw numbers, clinical response at week 8 was achieved in 40.2% (336/835) and 30.9% (201/650) of participants in the CZP and the placebo groups, respectively.In raw numbers, serious adverse events were observed in 8.7% (73/835) and 6.2% (40/650) of participants in the CZP and the placebo groups, respectively (RR 1.35, 95% CI 0.93 to 1.97; moderate certainty evidence). Serious adverse events included worsening Crohn's disease, infections, and malignancy. AUTHORS' CONCLUSIONS: Moderate certainty evidence suggests that CZP is effective for induction of clinical remission and clinical response in participants with active CD patients. It is uncertain whether the risk of serious adverse events differs between CZP and placebo as the 95% CI includes the possibility of a small decrease or doubling of events. Future studies are needed to evaluate the long-term efficacy and safety of CZP in CD patients.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Certolizumab Pegol/uso terapêutico , Doença de Crohn/tratamento farmacológico , Humanos , Fatores Imunológicos/uso terapêutico , Quimioterapia de Indução , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão
10.
N Engl J Med ; 381(10): 923-932, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31483963

RESUMO

BACKGROUND: Pulmonary alveolar proteinosis is a disease characterized by abnormal accumulation of surfactant in the alveoli. Most cases are autoimmune and are associated with an autoantibody against granulocyte-macrophage colony-stimulating factor (GM-CSF) that prevents clearing of pulmonary surfactant by alveolar macrophages. An open-label, phase 2 study showed some therapeutic efficacy of inhaled recombinant human GM-CSF in patients with severe pulmonary alveolar proteinosis; however, the efficacy in patients with mild-to-moderate disease remains unclear. METHODS: We conducted a double-blind, placebo-controlled trial of daily inhaled recombinant human GM-CSF (sargramostim), at a dose of 125 µg twice daily for 7 days, every other week for 24 weeks, or placebo in 64 patients with autoimmune pulmonary alveolar proteinosis who had a partial pressure of arterial oxygen (Pao2) while breathing ambient air of less than 70 mm Hg (or <75 mm Hg in symptomatic patients). Patients with severe pulmonary alveolar proteinosis (Pao2 <50 mm Hg) were excluded to avoid possible exacerbation of the disease in patients who were assigned to receive placebo. The primary end point was the change in the alveolar-arterial oxygen gradient between baseline and week 25. RESULTS: The change in the mean (±SD) alveolar-arterial oxygen gradient was significantly better in the GM-CSF group (33 patients) than in the placebo group (30 patients) (mean change from baseline, -4.50±9.03 mm Hg vs. 0.17±10.50 mm Hg; P = 0.02). The change between baseline and week 25 in the density of the lung field on computed tomography was also better in the GM-CSF group (between-group difference, -36.08 Hounsfield units; 95% confidence interval, -61.58 to -6.99, calculated with the use of the Mann-Whitney U test and the Hodges-Lehmann estimate of confidence intervals for pseudo-medians). Serious adverse events developed in 6 patients in the GM-CSF group and in 3 patients in the placebo group. CONCLUSIONS: In this randomized, controlled trial, inhaled recombinant human GM-CSF was associated with a modest salutary effect on the laboratory outcome of arterial oxygen tension, and no clinical benefits were noted. (Funded by the Japan Agency for Medical Research and Development and the Ministry of Health, Labor, and Welfare of Japan; PAGE ClinicalTrials.gov number, NCT02835742; Japan Medical Association Center for Clinical Trials number, JMA-IIA00205.).


Assuntos
Doenças Autoimunes/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Proteinose Alveolar Pulmonar/tratamento farmacológico , Administração por Inalação , Adulto , Idoso , Autoanticorpos/sangue , Doenças Autoimunes/diagnóstico por imagem , Método Duplo-Cego , Esquema de Medicação , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos e Macrófagos/efeitos adversos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Proteinose Alveolar Pulmonar/diagnóstico por imagem , Proteinose Alveolar Pulmonar/imunologia , Capacidade de Difusão Pulmonar , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Fumar/efeitos adversos , Tomografia Computadorizada por Raios X , Teste de Caminhada
11.
Ideggyogy Sz ; 72(7-8): 285-288, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31517463

RESUMO

Morvan syndrome is a rare disease characterized by peripheral nerve hyperexcitability, encephalopathy, dys-autonomia and significant insomnia. The patient, who was included in the present study, was followed-up at our clinics for confusion, myokymia, hyperhidrosis, epileptic seizures, tachycardia, agitation, hypokalemia, and hyponatremia. The cranial MRI of the patient demonstrated hyperintensities at the T2 and FLAIR sections of the medial temporal lobe and insular lobes. Electromyography and neurotransmission examination results were concordant with peripheral nerve hyperreactivity. Contactin-associated protein-like 2 antibodies and leucine-rich glioma inactivated protein 1 antibodies were detected as positive. The patient was diagnosed with Morvan syndrome; intravenous immunoglobulin and corticosteroid treatment was started. Almost full remission was achieved. This very rare syndrome implies challenges in diagnosis and treatment; however, remission can be achieved during the follow-up. In addition, caution is needed in the long-term follow-up of these patients regarding the development of malignancies.


Assuntos
Encefalopatias , Encéfalo/diagnóstico por imagem , Transtornos dos Movimentos/fisiopatologia , Doenças Musculares/fisiopatologia , Doenças do Sistema Nervoso Periférico/diagnóstico , Corticosteroides/uso terapêutico , Autoanticorpos/sangue , Eletromiografia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Encefalite Límbica , Transtornos dos Movimentos/tratamento farmacológico , Doenças Musculares/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Convulsões/etiologia , Resultado do Tratamento
12.
Presse Med ; 48(7-8 Pt 1): 825-831, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31447337

RESUMO

Diagnosis criteria have been revised in 2014 and allow the treatment of some asymptomatic patients. Since 2015, a new prognostic score includes tumor plasma cells chromosomal abnormalities. It helps in the distinction between "standard risk" and "high risk" myelomas. Scanner, MRI and Pet Scan are the radiological reference exams to evaluate bone involvement. Alkylating agents, immunomodulators, proteasome inhibitors, and monoclonal antibodies became the most important antitumoral treatments. Risk notion will become more and more important for therapeutic choices. These choices will depend on residual disease evaluation. The next decade will be the immunotherapies development decade.


Assuntos
Detecção Precoce de Câncer/tendências , Oncologia/tendências , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Terapias em Estudo/tendências , Anticorpos Monoclonais/uso terapêutico , Terapia Combinada/tendências , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/normas , Humanos , Fatores Imunológicos/uso terapêutico , Imunoterapia/métodos , Imunoterapia/tendências , Oncologia/métodos , Oncologia/normas , Mieloma Múltiplo/patologia , Guias de Prática Clínica como Assunto , Prognóstico , Terapias em Estudo/métodos
13.
Orv Hetil ; 160(34): 1335-1339, 2019 Aug.
Artigo em Húngaro | MEDLINE | ID: mdl-31423830

RESUMO

Introduction: Uveitis is characterized by inflammation of the middle layer of the eye. Its overall incidence is low. Autoimmune diseases and infections are the most common underlying diseases. Out of the autoimmune diseases, juvenile idiopathic arthritis is associated most frequently with uveitis. The topical ophthalmological treatment may fail in a significant proportion of the patients and immunomodulatory therapy may be required. Aim and method: In a retrospective study, data of 33 children diagnosed and treated with uveitis at the Department of Pediatrics and Ophthalmology, University of Pécs during the last 5 years were collected and analyzed. Results: The mean age of the patients was 9.3 (0.3-17.8) years. Boys and girls were equally affected with an exception of patients with juvenile idiopathic arthritis where female predominance was found. An underlying disease could be identified in 60% of the cases (20/33). Uveitis was associated in 12 patients with juvenile idiopathic arthritis, in 2 patients with Behcet's disease and in a single case with inflammatory bowel disease. Infections have been proven in 5 patients. The autoimmune diseases caused an eye inflammation typically in anterior localization, in contrast to the infections that resulted in posterior uveitis. The majority of the patients required systemic treatment. 3 of them received systemic corticosteroid and 18 patients methotrexate as disease-modifying antirheumatic drug. 13 children with severe disease activity required biological therapy (adalimumab injection). Remission could be achieved in 1.45 (0.75-2.5) months. Conclusion: Pediatric uveitis is of great importance. Early diagnosis, adequate therapy and follow-up require multidisciplinary cooperation. Orv Hetil. 2019; 160(34): 1335-1339.


Assuntos
Adalimumab/uso terapêutico , Artrite Juvenil/complicações , Terapia Biológica , Fatores Imunológicos/uso terapêutico , Imunomodulação , Uveíte/diagnóstico , Uveíte/tratamento farmacológico , Adolescente , Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Glucocorticoides/uso terapêutico , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Uveíte/complicações , Uveíte/etiologia
17.
Hematol Oncol ; 37(4): 345-351, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31283840

RESUMO

Based on results of two pilot trials, lenalidomide (LEN) was found to be active and safe as monotherapy and showed an increased response rate of 80% in combination with rituximab (R) for patients with mucosa-associated lymphoid tissue (MALT) lymphoma. While initial results were promising, there are currently no data on long-term outcome, and larger international phase II/III trials on LEN for indolent lymphoma lack specific subgroup analyses. Thus, we have systematically analyzed 50 patients treated with LEN-based therapy (LEN-monotherapy n = 16, R-LEN n = 34) at the Medical University of Vienna 2009 to 2019 and investigated long-term outcome and relapse patterns. At a follow-up of more than 5 years (median 68 months), 54% of patients are free of relapse, and estimated median progression-free survival (PFS) was 72 months (95%CI 49-96). There was no difference in PFS according to stage of disease, i.e. localized versus disseminated disease (P = .67) and previous systemic treatment (P = .16). Interestingly, but with the caveat of the limited number of patients included in this series, primary extragastric disease had a superior PFS compared with gastric lymphoma (P = .04) and also depth of response, i.e. complete or partial response versus stable disease was associated with significantly prolonged PFS (P = .01). We documented four patients (8%) with pronounced improvement of response during follow-up including three patients initially rated as partial remission and finally achieving complete remission at 12 to 32 months. This highlights the potential of delayed responses to LEN treatment. Estimated overall survival at 5 years was excellent at 92%. These "real-world" data confirm long-term activity of LEN in MALT lymphoma.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Lenalidomida/uso terapêutico , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Antineoplásicos/administração & dosagem , Áustria/epidemiologia , Avaliação de Medicamentos , Feminino , Seguimentos , Humanos , Fatores Imunológicos/administração & dosagem , Estimativa de Kaplan-Meier , Lenalidomida/administração & dosagem , Linfoma de Zona Marginal Tipo Células B/epidemiologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/epidemiologia , Intervalo Livre de Progressão , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento
18.
AIDS Rev ; 21(2): 65-75, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31332396

RESUMO

Thanks to the advancement in understanding of molecular mechanisms driving immune surveillance, we have now approached a revolutionary era for the treatment of malignant melanoma (MM). Meanwhile, people living with HIV/AIDS (PLWHA) are aging and non-AIDS-related cancers have become a leading cause of death. Both HIV infection and melanoma share common immune-pathological pathways: immune checkpoints are being targeted for melanoma immunotherapy and investigated as a "shock and kill" strategy for latency reversion among HIV-positive individuals. Nevertheless, a substantial lack of information exists on epidemiology, clinical features, and management of MM in HIV, due to compartmentalized approaches and poor awareness about the problem. In this narrative review, we aimed at analyzing available data regarding MM in PLWHA to point out key knowledge gaps and future opportunities from an integrated dermatology, oncology, and infectious diseases standpoint. To date, a strong association between HIV infection and MM risk still needs to be effectively demonstrated; nevertheless, once this cancer has developed in HIV-positive people, it shows more aggressive course, worse prognosis, and seemingly peculiar clinical and histological features. Despite these challenges, a syndemic framework should lead us toward a tailored and multidisciplinary approach not to miss valuable opportunities from the worst situations including the enrolment of HIV-positive patients in the ongoing trials with immune checkpoint inhibitors.


Assuntos
Gerenciamento Clínico , Infecções por HIV/complicações , Melanoma/diagnóstico , Melanoma/terapia , Ensaios Clínicos como Assunto , Humanos , Fatores Imunológicos/uso terapêutico , Melanoma/epidemiologia
19.
N Engl J Med ; 381(1): 36-46, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31269364

RESUMO

BACKGROUND: B-cell anomalies play a role in the pathogenesis of membranous nephropathy. B-cell depletion with rituximab may therefore be noninferior to treatment with cyclosporine for inducing and maintaining a complete or partial remission of proteinuria in patients with this condition. METHODS: We randomly assigned patients who had membranous nephropathy, proteinuria of at least 5 g per 24 hours, and a quantified creatinine clearance of at least 40 ml per minute per 1.73 m2 of body-surface area and had been receiving angiotensin-system blockade for at least 3 months to receive intravenous rituximab (two infusions, 1000 mg each, administered 14 days apart; repeated at 6 months in case of partial response) or oral cyclosporine (starting at a dose of 3.5 mg per kilogram of body weight per day for 12 months). Patients were followed for 24 months. The primary outcome was a composite of complete or partial remission of proteinuria at 24 months. Laboratory variables and safety were also assessed. RESULTS: A total of 130 patients underwent randomization. At 12 months, 39 of 65 patients (60%) in the rituximab group and 34 of 65 (52%) in the cyclosporine group had a complete or partial remission (risk difference, 8 percentage points; 95% confidence interval [CI], -9 to 25; P = 0.004 for noninferiority). At 24 months, 39 patients (60%) in the rituximab group and 13 (20%) in the cyclosporine group had a complete or partial remission (risk difference, 40 percentage points; 95% CI, 25 to 55; P<0.001 for both noninferiority and superiority). Among patients in remission who tested positive for anti-phospholipase A2 receptor (PLA2R) antibodies, the decline in autoantibodies to anti-PLA2R was faster and of greater magnitude and duration in the rituximab group than in the cyclosporine group. Serious adverse events occurred in 11 patients (17%) in the rituximab group and in 20 (31%) in the cyclosporine group (P = 0.06). CONCLUSIONS: Rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria at 12 months and was superior in maintaining proteinuria remission up to 24 months. (Funded by Genentech and the Fulk Family Foundation; MENTOR ClinicalTrials.gov number, NCT01180036.).


Assuntos
Ciclosporina/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Imunossupressores/uso terapêutico , Rituximab/uso terapêutico , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ciclosporina/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Imunossupressores/efeitos adversos , Infusões Intravenosas , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Proteinúria/tratamento farmacológico , Indução de Remissão , Rituximab/efeitos adversos , Falha de Tratamento , Adulto Jovem
20.
Postgrad Med ; 131(7): 486-489, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31353999

RESUMO

Objective: The objective of this study was to evaluate the efficacy and safety of rituximab (RTX) treatment given off-label to Cypriot patients with multiple sclerosis (MS). Methods: Clinical data from 30 MS patients ever treated with off-label RTX until mid-2018 at the Cyprus Institute of Neurology and Genetics were retrospectively collected and reviewed. The heterogeneous patient cohort included patients with relapsing-remitting MS (RRMS), primary progressive MS (PPMS) and secondary progressive MS (SPMS). Outcome data (relapse rate and EDSS progression) as well as adverse effects for patients with a follow-up period of >12 months (n = 13) were recorded. Results: Following RTX administration, all patients with RRMS remained relapse free and had a stable or slightly improved EDSS score (mean EDSS before treatment = 6, mean EDSS at 12 months = 4.75). Patients with SPMS had a significant reduction in their relapse rate and a stabilization or slight improvement of their EDSS scores (mean EDSS before treatment = 6.25, mean EDSS at 12 months = 5.5). Only one of the patients with PPMS had a follow-up period of >12 months and his EDSS score remained unchanged. Rituximab infusions were generally well tolerated; there were only seven grade 3 or 4 adverse events recorded. Conclusion: Our results are in agreement with larger retrospective studies in which it was demonstrated that RTX was well tolerated and effective in treating RRMS and SPMS patients by reducing relapse rate and stabilizing disease.


Assuntos
Fatores Imunológicos/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Rituximab/uso terapêutico , Adulto , Chipre , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/fisiopatologia , Uso Off-Label , Estudos Retrospectivos , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA