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1.
Medicine (Baltimore) ; 98(42): e17595, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626134

RESUMO

RATIONALE: Extremes of age is an important risk factor for the development of coronary arteries aneurysms (CAAs) associated to Kawasaki disease (KD) along with male gender, prolonged fever and a delay in diagnosis or treatment. PATIENT CONCERNS: We report two cases of KD in the extremes of age, a 5-month-old male infant and a 9-year-old child in order to underline the features of this disorder outside the typical age range of 1 to 4 years. The 5-month-old male was admitted in our clinic for generalized polymorphous exanthema and fever for approximately 7 days. The laboratory test pointed out leukocytosis and increased inflammatory biomarkers. The 9-year-old male child was admitted in our clinic for fever and submandibular adenopathy. The onset was approximately 5 days before the admission with a sudden development of unilateral, painless, submandibular lymphadenopathy for which the ENT specialist recommended antibiotics and nonsteroid anti-inflammatory drugs. In the 2nd day of admission, he presented severe desquamation of hands and soles. DIAGNOSIS: Both cases were diagnosed with KD. The echocardiography showed no cardiac impairment in the infant, while in the older patient it revealed mild dilation of the left coronary artery. INTERVENTIONS: Both patients received intravenously immunoglobulin and pulsed methylprednisolone. OUTCOMES: The evolution was favorable in both cases, but in the infant, the C-reactive protein levels persisted mildly elevated for approximately 2 months after the diagnosis. LESSONS: The peculiarities of KD in the extremes of age are related to a higher frequency of incomplete features and an increased incidence of coronary artery lesions resulting in a delay of the diagnosis, and subsequent poorer outcomes.


Assuntos
Aneurisma Coronário/diagnóstico , Imunoglobulinas Intravenosas/uso terapêutico , Metilprednisolona/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Criança , Aneurisma Coronário/tratamento farmacológico , Aneurisma Coronário/etiologia , Vasos Coronários/diagnóstico por imagem , Quimioterapia Combinada , Ecocardiografia , Seguimentos , Glucocorticoides/uso terapêutico , Humanos , Fatores Imunológicos , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico
2.
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
3.
Medicina (B Aires) ; 79(4): 299-302, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31487253

RESUMO

Cicatrizing conjunctivitis is the final consequence of several diseases. The most severe among them are cicatricial pemphigoid and chronic Stevens-Johnson syndrome. Systemic immunosuppressive drugs and steroids are usually an effective approach to these diseases. However, a few patients follow a recalcitrant course unremitting to usual therapy. We describe the treatment with rituximab of seven patients with cicatricial pemphigoid and two with chronic Stevens-Johnson syndrome. Eight of them also received gammaglobulin and all achieved clinical remission. Three relapsed and required two or three new courses of rituximab with good control of disease activity. Rituximab proved to be an efficacious drug for chronic recalcitrant cicatrizing conjunctivitis.


Assuntos
Cicatriz/tratamento farmacológico , Conjuntivite/tratamento farmacológico , Fatores Imunológicos/administração & dosagem , Penfigoide Mucomembranoso Benigno/complicações , Rituximab/administração & dosagem , Síndrome de Stevens-Johnson/complicações , Adulto , Idoso , Doença Crônica , Cicatriz/etiologia , Conjuntivite/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
4.
Ther Umsch ; 76(4): 195-198, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31498041

RESUMO

Immunotherapy - immune-related adverse events and their management Abstract. Checkpoint-Inhibition has become an important part of modern oncological treatment strategies for many patients with cancer. The development of this new class of anti-cancer drugs has begun for ten years and showed meanwhile a specific new side effect profile. Since the mode of action of checkpoint inhibitors is immune modulation the side effects are particularly different to so far established anti-cancer drugs. Because of the immunological nature of side effects, the spectrum is wide, and the symptoms are amble. Additionally, the side effects can appear at very different time points after the administration of the checkpoint inhibitor. Therefore, the recognition and the management are a new challenge for the care teams. Only if the whole care team is able to understand, diagnose and efficiently manage the side effects the therapeutic potential of this new class of anti-cancer drugs can be made useful for the patients. The article aims to provide information for the care teams to recognize and manage side effects of checkpoint-inhibitors.


Assuntos
Imunoterapia/efeitos adversos , Imunoterapia/métodos , Neoplasias/terapia , Humanos , Fatores Imunológicos , Oncologia , Síndromes Neurotóxicas/etiologia
5.
Isr Med Assoc J ; 21(7): 475-479, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31507124

RESUMO

BACKGROUND: Uveitis is an inflammatory disorder of the uveal tract of the eye that can affect both adults and children. Non-infectious uveitis can be an expression of a systemic autoimmune condition, or it can be idiopathic. It is a serious disease, associated with possible severe complications leading to visual impairment and blindness. For this reason, a prompt diagnosis and assessment of an appropriate treatment, with the collaboration of specialists such as ophthalmologists and rheumatologists, are extremely important. Many treatment options may be associated to side effects; therefore, clinicians should follow a stepladder approach starting with the least aggressive treatments to induce remission of inflammation. In this review, we reported the current evidence-based treatments for non-infectious uveitis in pediatric and adult patients with particular attention to the biologic response modifier treatment options. Important multicenter studies have demonstrated the efficacy of adalimumab, both in adults (VISUAL I, VISUAL II, VISUAL III) and in children (SYCAMORE, ADJUVITE), while for other agents data are still scarce.


Assuntos
Adalimumab/administração & dosagem , Fatores Imunológicos/administração & dosagem , Uveíte/tratamento farmacológico , Adulto , Criança , Comportamento Cooperativo , Medicina Baseada em Evidências , Humanos , Inflamação/tratamento farmacológico , Uveíte/diagnóstico , Uveíte/patologia
6.
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
7.
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
8.
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
9.
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
10.
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.
Magy Onkol ; 63(3): 165-171, 2019 Sep 18.
Artigo em Húngaro | MEDLINE | ID: mdl-31533135

RESUMO

In the immune defense against cancer, cell-mediated adaptive immune response is considered of primary importance, in which T lymphocytes play a key role. Activation, expansion and function of antigen-specific T cells is a multistep process and its outcome depends on the balance of positive and negative regulatory mechanisms controlling each step. Many factors can hamper the development of an efficient antitumor immune response, such as insufficient expression of tumor antigens or of molecules necessary for their processing, inhibitory molecular interactions (e.g. immune checkpoints), immune suppressive factors or suppressor cells. Various therapeutic strategies have been developed in order to increase the efficiency of antitumor immune defense, of which the application of immune checkpoint inhibitors, antibodies blocking the brakes of immune response, is the most widespread. These immunomodulatory antibodies had more favorable effect than traditional treatment modalities on a widening spectrum of tumor types, still the majority of patients do not or only transiently respond. Therefore, great efforts are made to develop rational combinations of immune and other therapies, and to identify resistance mechanisms and biomarkers predicting therapy outcome.


Assuntos
Imunoterapia , Neoplasias/imunologia , Neoplasias/terapia , Linfócitos T/imunologia , Antígenos de Neoplasias/imunologia , Humanos , Fatores Imunológicos/imunologia
13.
Magy Onkol ; 63(3): 217-223, 2019 Sep 18.
Artigo em Húngaro | MEDLINE | ID: mdl-31533142

RESUMO

Despite the spectacular development of clinical immunotherapy (IT) in the last decade, the regular treatment approaches for the most common central nervous system (CNS) tumors, the malignant gliomas (MGs) has not changed yet. The most important pitfalls of the routine application of immunotherapy can be imputed to the special and originally immunosuppressed microenvironment and the extreme heterogeneity of MGs, however the defensive role of the blood-brain barrier, the general usage of steroids and the difficulties in the evaluation of brain images can also play a role in these types of difficulties. Additionally, in the case of MGs, well-accepted IT biomarker assays (PDL1 positivity, mismatch repair deficiencies, tumor mutation burden, etc.) generally reveal only minimal levels of immunogen activities. Nevertheless, there are some promising results with the utilization of checkpoint inhibitors and other IT modalities (such as virus-based therapies, tumor vaccines, adoptive T cell therapies) and with the combination of conventional oncotherapy methods in case of CNS malignancies, as well. In conclusion, although the CNS is not any more considered as an "immunological sanctuary" and despite some encouraging experimental and clinical results in CNS oncotherapy, the routine application of IT in case of MGs is still awaited.


Assuntos
Neoplasias Encefálicas/terapia , Glioma/terapia , Imunoterapia , Neoplasias Encefálicas/imunologia , Glioma/imunologia , Humanos , Fatores Imunológicos/imunologia , Microambiente Tumoral/imunologia
14.
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
15.
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
16.
Wiad Lek ; 72(7): 1397-1402, 2019.
Artigo em Polonês | MEDLINE | ID: mdl-31398175

RESUMO

Recently, the intensive development of immunotherapies in the treatment of malignant tumors has been observed. The investigated treatment approaches including specific monoclonal antibodies, adoptive therapy and also anticancer vaccinations. The implementation of immunotherapy seems to be promising in treatment of the most malignant and fatal tumors including ovarian cancer. However, current findings have shown only a nonsignificant improvement of patients' survival. The possible cause of failure may be immunotherapy barriers that are a result of low immunogenicity level of ovarian cancer cells, mutation variability, and also the presence of a specific, immunosuppressive tumor microenvironment, which stimulates the cancer progression. The review presents the selected mechanisms of tumor resistance to immunological therapy. In order to project effective treatment approaches, it is necessary to understand both, mechanisms leading to the correct response for the treatment and causing therapeutic failures, resulting from resistance to therapy.


Assuntos
Imunoterapia , Neoplasias Ovarianas , Anticorpos Monoclonais , Feminino , Humanos , Fatores Imunológicos , Neoplasias Ovarianas/terapia , Microambiente Tumoral
17.
Cochrane Database Syst Rev ; 8: CD012448, 2019 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-31425625

RESUMO

BACKGROUND: Kawasaki disease (KD) is an acute inflammatory vasculitis (inflammation of the blood vessels) that mainly affects children between six months and five years of age. The vasculitis primarily impacts medium-sized blood vessels, especially in the coronary arteries. In most children, intravenous immunoglobulin (IVIG) and aspirin therapy rapidly reduce inflammatory markers, fever, and other clinical symptoms. However, approximately 15% to 20% of children receiving the initial IVIG infusion show persistent or recurrent fever and are classified as IVIG-resistant. Tumor necrosis factor-alpha (TNF-α) is an inflammatory cytokine that plays an important role in host defence against infections and in immune responses. Several studies have established that blocking TNF-α is critical for obtaining anti-inflammatory effects in children with KD, thus, there is a need to identify benefits and risks of TNF-α blockers for the treatment of KD. OBJECTIVES: To evaluate the efficacy and safety of using TNF-α blockers (i.e. infliximab and etanercept) to treat children with Kawasaki disease. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 19 September 2018. We also undertook reference checking of grey literature. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared TNF-α blockers (i.e. infliximab and etanercept) to placebo or other drugs (including retreatment with IVIG) in children with KD, reported in abstract or full-text. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the study selection criteria, assessed risk of bias and extracted data. When necessary, we contacted study authors for additional information. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included five trials from 14 reports, with a total of 494 participants. All included trials were individual RCTs that examined the effect of TNF-α blockers for KD.Five trials (with 494 participants) reported the incidence of treatment resistance. TNF-α blockers reduced the incidence of treatment resistance (TNF-α blocker intervention group 30/237, control group 58/257; risk ratio (RR) 0.57, 95% confidence interval (CI) 0.38 to 0.86; low-certainty evidence).Four trials reported the incidence of coronary artery abnormalities (CAAs). Three trials (with 270 participants) contributed data to the meta-analysis, since we could not get the data needed for the analysis from the fourth trial. There was no clear difference between groups in the incidence of CAAs (TNF-α blocker intervention group 8/125, control group 9/145; RR 1.18, 95% CI 0.45 to 3.12; low-certainty evidence).Three trials with 250 participants reported the adverse effect 'infusion reactions' after treatment initiation. The TNF-α blocker intervention decreased infusion reactions (TNF-α blocker intervention group 0/126, control group 15/124; RR 0.06, 95% CI 0.01 to 0.45; low-certainty evidence).Two trials with 227 participants reported the adverse effect 'infections' after treatment initiation. There was no clear difference between groups (TNF-α blocker intervention group 7/114, control group 10/113; RR 0.68, 95% CI 0.33 to 1.37; low-certainty evidence).One trial (with 31 participants) reported the adverse effect 'cutaneous reactions' (rash and contact dermatitis). There was no clear difference between the groups for incidence of rash (TNF-α blocker intervention group 2/16, control group 0/15; RR 4.71, 95% CI 0.24 to 90.69; very low-certainty evidence) or for incidence of contact dermatitis (TNF-α blocker intervention group 1/16, control group 3/15; RR 0.31, 95% CI 0.04 to 2.68; very low-certainty evidence).No trials reported other adverse effects such as injection site reactions, neutropenia, infections, demyelinating disease, heart failure, malignancy, and induction of autoimmunity. AUTHORS' CONCLUSIONS: We found a limited number of RCTs examining the effect of TNF-α blockers for KD. In summary, low-certainty evidence indicates that TNF-α blockers have beneficial effects on treatment resistance and the adverse effect 'infusion reaction' after treatment initiation for KD when compared with no treatment or additional treatment with IVIG. Further research will add to the evidence base. Due to the small number of underpowered trials contributing to the analyses, the results presented should be treated with caution. Further large high quality trials with timing and type of TNF-α blockers used are needed to determine the effects of TNF-α blockers for KD.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Pré-Escolar , Humanos , Fatores Imunológicos , Lactente , Ensaios Clínicos Controlados Aleatórios como Assunto , Vasculite/tratamento farmacológico
19.
Medicine (Baltimore) ; 98(34): e16888, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441865

RESUMO

RATIONALE: Facial nerve palsy (FNP) is one of the rare neurologic symptoms of Kawasaki disease (KD), associated with a higher incidence of coronary arteries lesions and may be an indicator of more severe disease. PATIENT CONCERNS: A 3-month-old male infant with persistent fever, irritability, and facial asymmetry. DIAGNOSES: KD with FNP. INTERVENTIONS: The infant received intravenous immunoglobulin (IVIG) (2 g/kg/16 hours) and aspirin (50 mg/kg/day) were started on the 8th day of illness. OUTCOMES: Fever and FNP resolved within 48 hours after IVIG treatment. The inflammatory markers all improved to normal or near-normal levels before discharge; all infectious studies returned negative. His left facial weakness was unappreciable at day of discharge. LESSONS: FNP associated with KD is an uncommon finding but may indicate an increased risk of coronary artery involvement. KD should always be kept in mind in the differential diagnosis of a child who presents with prolonged unexplained fever, even with incomplete diagnostic features, as well as the need to be aware of unusual manifestations, such as FNP.


Assuntos
Anomalias dos Vasos Coronários/etiologia , Assimetria Facial/etiologia , Paralisia Facial/etiologia , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Anomalias dos Vasos Coronários/diagnóstico por imagem , Ecocardiografia , Assimetria Facial/tratamento farmacológico , Paralisia Facial/tratamento farmacológico , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Fatores Imunológicos/administração & dosagem , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações
20.
Medicine (Baltimore) ; 98(34): e16906, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441871

RESUMO

RATIONALE: Brain abnormalities have frequently been reported in neuromyelitis optica spectrum disorders patients, but vertigo as an initial manifestation has rarely been described. PATIENT CONCERNS: A 64-year-old woman who initially presented with vertigo, then accompanied with other brainstem manifestations and spinal cord involvement. DIAGNOSES: MRI revealed medulla oblongata, cervical and thoracic spinal cord lesions. NMO-IgG antibody was seropositive. Taken her previous medical history and clinical manifestations into consideration, the patient was eventually diagnosed as neuromyelitis optica spectrum disorders. INTERVENTIONS: Before diagnosis, symptomatic treatment and acupuncture were adopted, whereas after diagnosis, steroid, intravenous immunoglobulin, and immunosuppressant were supplemented. OUTCOMES: Her dizziness, nausea and vomiting were gradually relieved by symptomatic treatment and acupuncture before the confirmed diagnosis and immunotherapy. After added treatment with steroid, immunosuppressant, especially intravenous immunoglobulin, diplopia and nystagmus disappeared, and superficial sensation was improving. She was fully recovered six months after admission. LESSONS: Vertigo as a rare prodrome of neuromyelitis optica spectrum disorders deserves attention. The symptoms and signs were improved by a combined treatment of steroid, immunosuppressant, acupuncture, and particularly intravenous immunoglobulin.


Assuntos
Neuromielite Óptica/diagnóstico , Vertigem/etiologia , Terapia por Acupuntura , Diplopia/etiologia , Diplopia/terapia , Feminino , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Fatores Imunológicos/administração & dosagem , Pessoa de Meia-Idade , Náusea/etiologia , Náusea/terapia , Neuromielite Óptica/tratamento farmacológico , Vértebras Torácicas/diagnóstico por imagem , Vertigem/terapia , Vômito/etiologia , Vômito/terapia
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