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1.
Rev. patol. respir ; 22(supl.2): S202-S210, jul. 2019. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-188013

RESUMO

La piedra angular del tratamiento de la enfermedad pulmonar obstructiva crónica (EPOC) es la broncodilatación, y en los últimos años se ha desarrollado un importante número de moléculas que han ido cambiando paulatinamente la práctica clínica habitual en estos pacientes. Los fármacos multivalentes con más de un mecanismo de acción broncodilatador representan el próximo paso en materia de relajación del músculo liso bronquial, pero dada la creciente evidencia sobre el estrés oxidativo y estado inflamatorio generalizado de la EPOC, existe una clara tendencia a demostrar el beneficio de formulaciones antiinflamatorias respecto a un potencial control sintomático, y secundariamente la reducción de la importante carga económica que supone el consumo de recursos sanitarios. En este capítulo se pretende dar un resumen esquemático y actualizado sobre los fármacos en investigación en EPOC en las fases previas de su desarrollo clínico


Bronchodilators are the cornerstone of Chronic obstructive pulmonary disease (COPD) treatment, and in the last years an important number of new molecules have changed gradually the clinical practice in these patients. Multivalent drugs with more than one mechanism of action represent the next step in terms of bronchial smooth muscle relaxation, although, giving the growing evidence of oxidative stress and generalized inflammation in COPD, there is a clear tendency to test the potential benefit of new anti-inflammatory drugs for symptoms control in the first place and consequently the reduction of the high economic burden of this disease. This chapter aims to give a schematical and updated review of new drugs for COPD in the preclinical phases of their clinical development


Assuntos
Humanos , Drogas em Investigação/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Relaxamento Muscular/efeitos dos fármacos , Broncodilatadores/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Receptores do Fator de Necrose Tumoral/antagonistas & inibidores , Interleucina-1/antagonistas & inibidores , Interleucina-13/antagonistas & inibidores , Interleucinas/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Inibidores de Fosfodiesterase/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos
2.
Reumatol. clín. (Barc.) ; 13(2): 78-84, mar.-abr. 2017. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-161414

RESUMO

Objetivos. Evaluar la eficacia del tratamiento con tocilizumab (TCZ) en pacientes con artritis reumatoide (AR) en práctica clínica, las tasas de supervivencia del fármaco y variables clínicas predictoras de respuesta. Métodos. Es un estudio descriptivo, prospectivo, longitudinal y abierto en el que se incluyó a pacientes en condiciones de práctica clínica que recibieron TCZ (8mg/kg/cada 4 semanas). Las respuestas clínicas se midieron utilizando los criterios de respuesta de la European League Against Rheumatism (EULAR), las tasas de actividad baja y remisión según el Disease activity score-28 (DAS28-VSG) y Clinical Disease Activity Index (CDAI). Resultados. La tasa de respuesta EULAR fue del 86,63%, con una tasa de remisión DAS28 del 53,7% a los 6 meses de tratamiento. El 52,9% de los pacientes presentaron baja actividad de la enfermedad a los 24 meses según CDAI y 47,1% según DAS28. No hubo diferencias significativas en cuanto a respuesta EULAR, baja actividad y remisión DAS28 entre pacientes en tratamiento con TCZ en monoterapia y terapia combinada, ni entre pacientes positivos y negativos para factor reumatoide (FR) y/o anticuerpo antipéptido cíclico citrulinado (anti-PCC). Los pacientes que recibieron TCZ de primera línea presentaron mejores tasas de remisión y baja actividad a los 6 meses. La tasa de supervivencia fue del 61% a los 24 meses, siendo una de las causas de discontinuación más frecuente los efectos adversos. Conclusión. El TCZ es efectivo en pacientes con AR, tiene eficacia similar cuando se utiliza en monoterapia o en combinación con fármacos antirreumáticos modificadores de la enfermedad (FAME) sintéticos y presenta altas tasas de supervivencia (AU)


Objectives. To evaluate the efficacy of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in clinical practice, retention rates of the drug and predictors of response. Methods. We performed a descriptive, prospective, longitudinal, open-label study in patients receiving TCZ (8mg/kg/4 weeks) in a clinical practice setting. The clinical responses were evaluated using the European League Against Rheumatism (EULAR) response criteria, and the low activity and remission rates according to the Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) and the Clinical Disease Activity Index (CDAI). Results. The EULAR response rate was 86.63% and the DAS28 remission rate was 53.7% after 6 months of treatment; rates of low disease activity were 52.9% on CDAI and 47.1% on DAS28 at month 24. There were no statistically significant differences in EULAR response, rates of low activity and remission on DAS28 between patients receiving TCZ alone and those receiving TCZ in combination therapy, or between patients positive or negative for rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP) antibodies. The naïve biological therapy patients showed better remission and low activity rates after 6 months of treatment. The retention rate was 61% at month 24. Adverse events were among the most frequent causes of discontinuation. Conclusions. Tocilizumab is effective in RA, has a similar efficacy when used alone or in combination with synthetic disease-modifying antirheumatic drugs (DMARDs) and shows high retention rates (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Artrite Reumatoide/tratamento farmacológico , Antirreumáticos/uso terapêutico , Receptores do Fator de Necrose Tumoral/antagonistas & inibidores , Resultado do Tratamento , Fator de Necrose Tumoral alfa/administração & dosagem
3.
Actas dermo-sifiliogr. (Ed. impr.) ; 108(3): 184-191, abr. 2017. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-161634

RESUMO

La enfermedad inflamatoria intestinal es una entidad compleja que incluye la enfermedad de Crohn y la colitis ulcerosa, y se caracteriza por un estado proinflamatorio crónico con un curso oscilante y que en muchas ocasiones conlleva una gran morbilidad a estos pacientes. En la última década se han identificado distintas dianas terapéuticas que permiten el uso de fármacos biológicos, en particular los anticuerpos dirigidos contra el factor de necrosis tumoral alfa, que se asocian en un 5% de los casos con reacciones paradójicas psoriasiformes, que requieren una estrecha colaboración entre el dermatólogo y el gastroenterólogo en la toma de decisiones. La enfermedad inflamatoria intestinal se asocia, asimismo, a otras diversas manifestaciones dermatológicas y reumatológicas, y presenta una asociación genética y patogénica con la psoriasis, que justifica tanto el abordaje interdisciplinario de estos pacientes como la presente revisión (AU)


Inflammatory bowel disease (IBD) is a complex entity that includes Crohn disease and ulcerative colitis. It is characterized by a chronic proinflammatory state of varying intensity that often leads to considerable morbidity. In the last decade, several therapeutic targets have been identified that are susceptible to the use of biological agents, including anti-tumor necrosis factor alpha antibodies, which are associated with paradoxical psoriasiform reactions in 5% of patients. Decision-making in the management of these cases requires close collaboration between the dermatologist and gastroenterologist. Inflammatory bowel disease is also associated with various other dermatologic and rheumatologic manifestations, and presents a genetic and pathogenic association with psoriasis that justifies both the interdisciplinary approach to these patients and the present review (AU)


Assuntos
Humanos , Masculino , Feminino , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/etiologia , Doenças Inflamatórias Intestinais/patologia , Receptores do Fator de Necrose Tumoral/análise , Doença de Crohn/complicações , Colite Ulcerativa/complicações , Comorbidade , Psoríase/complicações , Espondiloartropatias/complicações
4.
Clin. transl. oncol. (Print) ; 18(10): 988-995, oct. 2016. tab, graf
Artigo em Inglês | IBECS | ID: ibc-155961

RESUMO

Purpose: hENT1 is a transmembrane protein which acts as a nucleoside transporter and is the main mediator of Gemcitabine (GEM) uptake into human cells. In this retrospective study we compared GEM versus FOLFIRINOX in patients with metastatic pancreatic cancer in which hENT1 evaluation was available. Methods: 149 patients affected by unresectable metastatic pancreatic cancer, treated in our institution from 2009 to 2013, have been screened for inclusion in this retrospective study. Seventy patients, treated with GEM or FOLFIRINOX in first-line therapy, fulfilled clinical inclusion criteria for survival analysis. Thirty-one patients were available and contained sufficient quality/quantity RNA for evaluation of hENT1 expression by RT-PCR. The primary endpoint was OS and the secondary endpoint was PFS. Results: The survival analysis, carried out on 70 patients regardless of hENT1 expression, showed a statistically longer OSandPFS in the group treated with FOLFIRINOX compared to GEM. Within the exploratory analysis, which included 31 patients, no differences were found in hENT1 positive patients treated with FOLFIRINOX compared to GEM in terms of OS (8.5 vs 7 months, HR: 0.89; 95 % CI 0.3-2.5; p = 0.8) and PFS (5.5 vs 5 months, HR: 0.8, 95 % CI 0.2-2.2; p = 0.61). GEM-treated hENT1 positive patients showed a statistically significant improvement both of OS (8 vs 2 months; p = 0.0012) and PFS (5 vs 1 months; p = 0.0004) in comparison to GEM-treated hENT1 negative patients. Conclusions: In our exploratory analysis GEM seems as effective as FOLFIRINOX in terms of survival with a better safety profile in hENT1 positive metastatic pancreatic cancer (AU)


No disponible


Assuntos
Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Metástase Neoplásica/tratamento farmacológico , Antineoplásicos/farmacocinética , Transportador Equilibrativo 1 de Nucleosídeo/análise , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Antígenos CD/análise , Receptores do Fator de Necrose Tumoral/análise , Proteínas de Transporte de Nucleosídeos/fisiologia
6.
Rev. esp. enferm. dig ; 108(3): 129-132, mar. 2016. tab, graf
Artigo em Inglês | IBECS | ID: ibc-148605

RESUMO

Background: Golimumab is a TNF-blocking agent indicated as a second-line therapy in ulcerative colitis. Purpose: To research the effectiveness and safety of golimumab in patients with ulcerative colitis in clinical practice. Methods: Retrospective study of the effectiveness and safety of golimumab in patients with ulcerative colitis. All patients received golimumab 200 mg subcutaneously at week 0, and golimumab 100 mg subcutaneously at week 2. After the induction treatment, each patient received 50 mg sc. every 4 weeks in patients with body weight less than 80 kg, and 100 mg every 4 weeks in patients with body weight greater than or equal to 80 kg. Results: Study of a group of 23 ulcerative colitis patients, 7 of whom were naive to any anti-TNF therapy, and 16 patients who had previously been treated with an anti-TNF agent other than golimumab (non-naive patients). The average treatment time with golimumab was 14.3 weeks. Globally, withdrawal of corticosteroids was observed in 74% of cases. Clinical response was observed in 85.5% of patients who had not received biological treatment previously, and in patients who had previously received biological treatment the response rate was 75%. Conclusions: In this short study, golimumab seems to be an alternative treatment in naive and non-naive anti-TNF ulcerative colitis patients. It is also a safe therapy, given that there were no adverse effects in the patients studied (AU)


No disponible


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Receptores do Fator de Necrose Tumoral/análise , Receptores do Fator de Necrose Tumoral , Fator 1 Associado a Receptor de TNF/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Resultado do Tratamento , Avaliação de Eficácia-Efetividade de Intervenções , Estudos Retrospectivos , Corticosteroides/uso terapêutico , Azatioprina/uso terapêutico
7.
Reumatol. clin., Supl. (Barc.) ; 11(supl.1): 36-41, ene. 2016. tab
Artigo em Espanhol | IBECS | ID: ibc-153466

RESUMO

A pesar de la falta de evidencia sólida en la bibliografía, las recomendaciones de los diferentes grupos internacionales para el tratamiento de la artritis psoriásica sitúan al metotrexato como el fármaco de primera elección. La experiencia clínica acumulada por los reumatólogos con el metotrexato, su perfil de seguridad y el nivel de retención que demuestran los registros nacionales, avalan dicha posición en el algoritmo terapéutico. Sin embargo faltan evidencias sobre su eficacia en otras manifestaciones extraarticulares de la artritis psoriásica, por lo que no se recomienda para el tratamiento de la entesitis ni de la espondilitis. En artritis psoriásica, a diferencia de la artritis reumatoide, no se ha demostrado que el tratamiento combinado sea superior al anti-TNFa. Sin embargo, el metotrexato puede alargar la supervivencia de los fármacos anti-TNFa, fundamentalmente la de los anticuerpos. Se requieren ensayos clínicos controlados para determinar la eficacia del metotrexato en la entesitis y dactilitis psoriásica, así como su papel en la terapia combinada (AU)


Despite the lack of solid evidence in the literature, methotrexate (MTX) is recommended as the first choice drug for the treatment of psoriatic arthritis (PsA) by distinct international groups. This position in the therapeutic algorithm is supported by the clinical experience of MTX accumulated by rheumatologists, its safety profile and retention level shown by national registries. However, there is a lack of evidence on the effectiveness of MTX in other extra-articular manifestations of PsA and therefore it is not recommended for the treatment of enthesitis and spondylitis. Combination therapy has not been shown to be superior to anti-TNFa therapy in PsA, unlike rheumatoid arthritis. However, MTX may prolong the survival of anti-TNFa drugs, mainly that of antibodies. Controlled clinical trials are required to determine the efficacy of MTX in enthesitis and psoriatic dactylitis, as well as its role in combination therapy (AU)


Assuntos
Humanos , Masculino , Feminino , Metotrexato/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Prática Clínica Baseada em Evidências/métodos , Quimioterapia Combinada/instrumentação , Quimioterapia Combinada/métodos , Tolerância a Medicamentos/imunologia , Tolerância a Medicamentos/fisiologia , Eficácia/métodos , Eficácia/tendências , Resultado do Tratamento , Algoritmos , Fator de Necrose Tumoral alfa , Receptores do Fator de Necrose Tumoral , Infusões Parenterais
8.
Actas dermo-sifiliogr. (Ed. impr.) ; 106(10): 823-829, dic. 2015. tab
Artigo em Espanhol | IBECS | ID: ibc-146618

RESUMO

INTRODUCCIÓN Y OBJETIVO: Los agentes biológicos anti-TNF usados para el tratamiento de la psoriasis moderada y grave pueden incrementar el riesgo de desarrollar tuberculosis activa en pacientes con infección tuberculosa latente. El objetivo principal de este estudio fue estimar la prevalencia de infección tuberculosa latente en pacientes con psoriasis en placas moderada y grave en consultas de dermatología en España. MATERIAL Y MÉTODO: Estudio epidemiológico, no intervencionista, de corte transversal y ámbito nacional, realizado en España en 2011-2012. Se incluyeron pacientes con psoriasis en placas moderada y grave, a los que se les había realizado en los 2 años previos a su inclusión en el estudio al menos una prueba de tuberculina y/o una prueba de liberación de IFN-γ mediante la técnica de ELISA QuantiFERON®-TB gold In Tube. RESULTADOS: Se incluyeron 440 pacientes evaluables. Se había realizado una prueba de tuberculina al 97,7% de los pacientes, resultando positiva en el 23%. En 238 pacientes con una primera prueba negativa se realizó un booster, que fue positivo en el 5%. Se realizó la determinación del QuantiFERON®-TB al 16,8% de los pacientes, resultando positivo en el 20,5%; en 2 de estos pacientes la prueba de la tuberculina había sido negativa. En el total de la muestra, la prevalencia de infección tuberculosa latente fue del 26,6%. El grado de concordancia entre la prueba de tuberculina y el QuantiFERON®-TB fue medio (índice kappa = 0,516; p < 0,001). CONCLUSIONES: La prevalencia de infección tuberculosa latente estimada en este estudio fue similar a la comunicada previamente en España


BACKGROUND AND OBJECTIVE: Anti-tumor necrosis factor therapy for moderate to severe psoriasis can increase the risk of active tuberculosis in patients who have latent tuberculosis infection (LTBI). The main objective of this study was to estimate the prevalence of LTBI in patients with moderate to severe plaque psoriasis being treated in dermatology clinics in Spain. MATERIAL AND METHOD: Non-interventional, cross-sectional, national epidemiological study conducted in Spain in 2011-2012. Patients with moderate to severe plaque psoriasis were included if they had undergone at least one tuberculin skin test (TST) and/or been evaluated with an interferon-γ release assay (IGRA) based on enzyme-linked immunosorbent assay (QuantiFERON® TB Gold In-Tube) in the 2 years preceding the study. RESULTS: Data for 440 patients were valid for analysis. In total, 97.7% of the patients had undergone a TST, with a positive result in 23%. Of the 238 patients in whom the initial result was negative, 5% converted to positive on re-testing for a booster effect. IGRA results were available for 16.8%, 20.5% of them positive. Two of the patients with positive IGRA results had a negative TST. The prevalence of LTBI in the whole sample was 26.6%. The degree of concordance between the TST and the IGRA was moderate (Kappa=0.516; P<.001). CONCLUSIONS: The prevalence of LTBI in this study was similar to previous estimates for Spain


Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tuberculose Latente/complicações , Tuberculose Latente/epidemiologia , Psoríase/complicações , Psoríase/diagnóstico , Psoríase/prevenção & controle , Receptores do Fator de Necrose Tumoral/administração & dosagem , Receptores do Fator de Necrose Tumoral/análise , Receptores do Fator de Necrose Tumoral/isolamento & purificação , Estudos Transversais/métodos , Estudos Transversais/tendências , Ensaio de Imunoadsorção Enzimática/métodos , Análise Estatística , Modelos Logísticos
10.
Rev. esp. enferm. dig ; 107(9): 527-533, sept. 2015. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-140748

RESUMO

Introducción: la intensificación del tratamiento con infliximab (IFX) en la colitis ulcerosa (CU) es más frecuente de lo establecido en estudios pivotales. Objetivos: establecer la frecuencia y forma con la que intensificamos en CU en práctica clínica, los factores predictores y comparar la evolución entre los pacientes con tratamiento intensificado y no intensificado. Métodos: estudio retrospectivo de 10 hospitales y 144 pacientes con respuesta a la inducción con IFX. Se analizaron variables predictoras de la intensificación con análisis de regresión de Cox. Se comparó la evolución, pérdida de respuesta a IFX y colectomía según tratamiento intensificado o no intensificado. Resultados: tiempo de seguimiento desde la inducción hasta la recogida de datos: 38 meses [rango intercuartil (RIC) 20-62]. Tiempo de tratamiento con IFX: 24 meses (RIC, 10-44). El 37% de los pacientes requirió intensificación. Se acortó el intervalo en 36 pacientes, se aumentó la dosis en 7, ambas en 10. La introducción simultánea de inmunosupresores tiopurínicos (INM) e IFX predijo la intensificación de forma independiente [Hazard ratio (HR) 0,034 p 0,006 IC 0,003-0,371]. En los pacientes con tratamiento intensificado fue más frecuente la suspensión de IFX por pérdida de respuesta (30,4% vs. 10,2% p 0,002), la reintroducción de corticoides (35% vs. 18%, p 0,018) y la colectomía (22% vs. 6,4% p 0,011). El 17% de los pacientes intensificados volvió a recibir 5 mg/kg cada 8 semanas. Conclusiones: la intensificación es frecuente y en ocasiones reversible. La introducción del INM en el momento de la inducción con IFX predice la no intensificación. La intensificación, aunque eficaz, se asocia a una peor evolución (AU)


Introduction: Infliximab (IFX) therapy intensification in ulcerative colitis (UC) is more common than established in pivotal studies. Objectives: To establish the frequency and form of intensification for UC in clinical practice, as well as predictors, and to compare outcomes between intensified and non-intensified treatment. Methods: A retrospective study of 10 hospitals and 144 patients with response to infliximab (IFX) induction. Predictive variables for intensification were analyzed using a Cox regression analysis. Outcome, loss of response to IFX, and colectomy were compared between intensified and non-intensified therapy. Results: Follow-up time from induction to data collection: 38 months [interquartile range (IQR), 20-62]. Time on IFX therapy: 24 months (IQR, 10-44). In all, 37% of patients required intensification. Interval was shortened for 36 patients, dose was increased for 7, and 10 subjects received both. Concurrent thiopurine immunosuppressants (IMM) and IFX initiation was an independent predictor of intensification [Hazard ratio, 0.034; p, 0.006; CI, 0.003-0.371]. In patients on intensified therapy IFX discontinuation for loss of response (30.4% vs. 10.2%; p, 0.002), steroid reintroduction (35% vs. 18%; p, 0.018), and colectomy (22% vs. 6.4%; p, 0.011) were more common. Of patients on intensification, 17% returned to receiving 5 mg/kg every 8 weeks. Conclusions: Intensification is common and occasionally reversible. IMM initiation at the time of induction with IFX predicts non-intensification. Intensification, while effective, is associated with poorer outcome (AU)


Assuntos
Adulto , Feminino , Humanos , Masculino , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/prevenção & controle , Colectomia/métodos , Colectomia , Corticosteroides/uso terapêutico , Estudos Retrospectivos , Análise de Regressão , Receptores do Fator de Necrose Tumoral/uso terapêutico , Análise Multivariada
11.
Clin. transl. oncol. (Print) ; 17(8): 547-667, ago. 2015. ilus
Artigo em Inglês | IBECS | ID: ibc-138181

RESUMO

Purpose. Human Apo2-Ligand/TRAIL secreted by natural killer cells and cytotoxic T lymphocytes plays an important role immunosurveillance controlling tumor growth and metastasis. Moreover, the fact that Apo2L/TRAIL is capable of inducing cell death in tumor cells but not in normal cells makes this death ligand a promising anti-tumor agent. Previous data from our group demonstrated that Apo2L/TRAIL was physiologically released as transmembrane protein inserted in lipid vesicles, called exosomes. Recently, we demonstrated that artificial lipid nanoparticles coated with bioactive Apo2L/TRAIL (LUV-TRAIL) resembling the natural exosomes, greatly improved Apo2L/TRAIL activity and were able to induce apoptosis in hematological malignancies. In this study, we have deepened in the underlying mechanism of action of LUV-TRAIL in hematologic cells. Methods/patients. Cytotoxic ability of LUV-TRAIL was assessed on Jurkat cells either over-expressing the anti-apoptotic protein Mcl1 or down-regulating the pro-apoptotic protein Bim previously generated in our laboratory. We also tested LUV-TRAIL cytotoxic ability against primary human leukemic cells from T-cell ALL patient. Results. Silencing Bim but not Mcl-1 over-expression partially protects Jurkat cells from apoptosis induced by sTRAIL. LUV-TRAIL induced caspase-8 and caspase-3 activation and killed Jurkat-Mcl1 and Jurkat-shBim more efficiently than sTRAIL independently of the mitochondrial pathway. On the other hand, LUV-TRAIL were clearly more cytotoxic against primary leukemic cells from a T-cell ALL patient than sTRAIL. Conclusion. Tethering Apo2L/TRAIL to the surface of lipid nanoparticles greatly increases its bioactivity and could be of potential use in anti-tumor therapeutics (AU)


No disponible


Assuntos
Feminino , Humanos , Masculino , Imunoterapia/métodos , Lipossomos , Receptores do Fator de Necrose Tumoral/análise , Testes Imunológicos de Citotoxicidade/métodos , Morte Celular , Imunoterapia , Apoptose , Forma do Núcleo Celular , Western Blotting/métodos , Análise Estatística
12.
Clin. transl. oncol. (Print) ; 17(8): 668-672, ago. 2015. tab
Artigo em Inglês | IBECS | ID: ibc-138182

RESUMO

Purpose. To assess the clinical results in terms of local control, toxicity, failure pattern and toxicity of SBRT in oligometastatic patients with inoperable lung metastases. Methods. Forty-four patients were treated (53 metastases). Dose regimen: 5 × 12 Gy (66 %), 8 × 7.5 Gy (20.8 %) and 10 × 5 Gy (13.2 %). Response was assessed using PET/CT at 6 months after SBRT. Results. Local control at 1 and 2 years was 86.7 %. Seventy-five percent of local failures had received a BED <105 Gy. After a median follow-up of 13.3 months, 25 % experienced distant progression. Overall survival at 1 and 2 years was 86.7 and 60.4 %, and cancer-specific survival was 95.3 and 75.2 %, respectively. Grade 2 toxicity was 6.8 %. There was no grade 3–4 toxicity. Conclusion. SBRT is effective and safe. The main failure pattern is distant progression. The selection of patients with a high probability of remaining oligometastatic is crucial for the efficiency of SBRT, both clinically and in terms of resources (AU)


No disponible


Assuntos
Feminino , Humanos , Masculino , Neoplasias Pulmonares/diagnóstico , Metástase Neoplásica/radioterapia , Receptores do Fator de Necrose Tumoral/análise , Testes Imunológicos de Citotoxicidade/métodos , Morte Celular , Radioterapia , Radiocirurgia , Radiocirurgia/métodos , Neoplasias Pulmonares/radioterapia , Tomografia Computadorizada de Emissão , Prognóstico
13.
Rev. clín. esp. (Ed. impr.) ; 213(7): 338-346, oct. 2013.
Artigo em Espanhol | IBECS | ID: ibc-115616

RESUMO

Las vasculitis de grandes vasos incluyen las arteritis de Takayasu y la de células gigantes. La arteritis de Takayasu afecta a niños y mujeres menores de 40 años, presenta una baja incidencia en el sur de Europa, y afecta principalmente a la aorta y sus ramas principales. La arteritis de células gigantes es la vasculitis más frecuente en los mayores de 60 años, con una incidencia mayor que la arteritis de Takayasu en la población europea. Afecta principalmente los vasos extracraneales, especialmente, los derivados de la carótida. Ambas entidades presentan inflamación a nivel de la pared vascular, lo que ocasiona el daño estructural y la expresión de un amplio espectro de manifestaciones clínicas. El tratamiento de elección de ambas entidades se basa en el uso de glucocorticoides a dosis elevadas asociados con frecuencia a inmunosupresores. La utilización de tratamientos biológicos se reservará para los casos refractarios al tratamiento convencional (AU)


The term large vessel vasculitidis includes two distinct clinical entities: Takayasu's arteritis and giant cell arteritis. Takayasu's arteritis mainly affects children and women under 40 years, affecting the aorta and its major branches. Its incidence in Southern Europe is low. Giant cell arteritis is the most common vasculitis in those 60. Its incidence in the European population is greater than that of Takayasu's arteritis. It mainly affects the extracranial vessels, especially those derived from the carotid artery. Both conditions are characterized by inflammation of the vessel wall, this causing structural damage and the expression of different clinical manifestations. The treatment of choice of both conditions is based on high-dose glucocorticoids associated, in some cases, to immunosuppressants. Biologic agents have been reserved for cases refractory to conventional therapies (AU)


Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Vasculite/terapia , Arterite de Takayasu/complicações , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/terapia , Glucocorticoides/uso terapêutico , Receptores de Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Células Gigantes/patologia , Células Gigantes , Receptores do Fator de Necrose Tumoral/uso terapêutico , Corticosteroides/uso terapêutico , Tomografia Computadorizada de Emissão , Metotrexato/uso terapêutico , Algoritmos
16.
Reumatol. clín. (Barc.) ; 9(2): 101-105, mar.-abr. 2013.
Artigo em Espanhol | IBECS | ID: ibc-110341

RESUMO

El tratamiento de la artritis reumatoide con un objetivo o estrategia «treat to target» es una propuesta importada de la literatura cardiovascular y endocrina. Se propone que la meta terapéutica en artritis reumatoide debería ser la remisión clínica o alternativamente un estado de bajo nivel de actividad clínica. El reumatólogo debería medir y documentar la actividad de la enfemedad en cada visita y, si el paciente no ha alcanzado la meta deseada, deberían hacerse los ajustes terapéuticos para lograrla. Las evidencias actuales en ensayos clínicos y meta-análisis apoyan que esta estrategia tiene beneficios clínicos importantes en pacientes con artritis reumatoide temprana cuando se compara con el tratamiento médico habitual. También se describe que el utilizar un tratamiento protocolizado reporta mayores beneficios. Se presentan elementos de una implementación exitosa en cohortes de artritis reumatoide temprana en Holanda. Se discute la necesidad de tener más información del beneficio en pacientes con artritis reumatoide establecida (AU)


Treating rheumatoid arthritis (RA) with a goal or “Treat to target” strategy is a therapeutic proposal taken from cardiovascular and endocrine literature. It proposes that the therapeutic target in RA should be a state of remission, or an alternative goal could be a low disease activity. Rheumatologists should measure and register disease activity in every clinical visit and if the goal has not been reached, therapeutic adjustments should be made. Current evidence from clinical trials and a meta-analysis supports the notion that this strategy has important clinical benefits in patients with early RA when compared with routine care. It is also described that using protocolized treatment offers greater benefits. Recent data from Dutch cohorts is presented showing its successful implementation. A discussion is offered on the need of more studies in established RA (AU)


Assuntos
Humanos , Masculino , Feminino , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/prevenção & controle , Fator de Necrose Tumoral alfa/uso terapêutico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Glucocorticoides/uso terapêutico , Encaminhamento e Consulta/normas , Encaminhamento e Consulta/tendências , Encaminhamento e Consulta , Estudos de Coortes , Protocolos Clínicos , Sistemas de Saúde/normas , Sistemas de Saúde/tendências , Algoritmos
17.
Reumatol. clín. (Barc.) ; 9(2): 106-112, mar.-abr. 2013. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-110342

RESUMO

La artritis reumatoide (AR) es una enfermedad sistémica e inflamatoria que afecta la membrana sinovial de las articulaciones, los tendones y algunos sitios extra-articulares. La prevalencia de la AR en Latinoamérica se encuentra entre 0.4–1.6%. El tratamiento precoz de la enfermedad se traduce en una reducción del costo para la sociedad. En vista de esto, se han establecido clínicas de AR temprana en varios países de la región. Se han identificado barreras para el tratamiento de la AR como lo son el retraso en la referencia al reumatólogo y limitaciones en el acceso al tratamiento. Varios países han desarrollado y adaptado guías para el tratamiento basadas en la evidencia y en sus propias realidades. La necesidad de tener registros detallados de las prescripciones de biológicos ha sido abordada con registros de biológicos lo que llevará a un mejor entendimiento de las enfermedades reumáticas y su tratamiento. Los biológicos disponibles en la actualidad son los inhibidores del factor de necrosis tumoral (TNF)-alpha (etanercept, infliximab y adalimumab), un agente depletor de células B (rituximab), un bloqueador del receptor de interleucina-6 (tocilizumab) y un bloqueador de la co-estimulación de células T (abatacept). En el futuro se incluirán los inhibidores de cinasas (tofacitinib y fostamatinib) e inhibidores del TNF-alpha alternativos (golimumab y certolizumab) y biosimilares (AU)


Rheumatoid arthritis (RA) is a systemic inflammatory disease affecting the synovium of joints, tendons, and some extra-articular sites. RA prevalence in Latin America ranges from 0.4 to 1.6%. Early treatment of RA translates into a substantial reduction in the cost to society. In light of this, early disease clinics are being established in some countries. Barriers to RA management, such as delay in referral to rheumatologists and limited access to therapy, have been identified. Evidence-based treatment guidelines have been adapted by countries according to their own situations. The need for keeping accurate records of biologics prescribed has been addressed by biologic registries, thereby contributing toward a better understanding of rheumatic diseases and their treatment. Current biologics include the tumor necrosis factor (TNF)-alpha inhibitors (etanercept, infliximab, and adalimumab), B-cell depletion agent (rituximab), interleukin-6 receptor blocker (tocilizumab), and T-cell co-stimulatory blocker (abatacept). Future therapies include kinase inhibitors (tofacitinib and fostamatinib), alternative TNF-alpha inhibitors (golimumab and certolizumab), and biosimilars (AU)


Assuntos
Humanos , Masculino , Feminino , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/prevenção & controle , Diagnóstico Precoce , Interleucinas/uso terapêutico , Receptores de Interleucina/uso terapêutico , Fatores Socioeconômicos , América Latina/epidemiologia , Artrite Reumatoide/economia , Fator de Necrose Tumoral alfa/uso terapêutico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Análise Socioeconômica
18.
Reumatol. clín. (Barc.) ; 9(2): 117-119, mar.-abr. 2013.
Artigo em Espanhol | IBECS | ID: ibc-110344

RESUMO

Se presentan un caso de dermatomiositis y otro de polimiositis refractarias a varios inmunosupresores convencionales y con respuesta a tratamiento con rituximab, con el que se posibilita la disminución de dosis de corticoide y se mantiene a la enfermedad en remisión durante un largo periodo (AU)


We report one case of dermatomyositis and one of polymyositis refractory to several conventional inmunosupressive therapies, which present a response after treatment with rituximab, enabling steroid dose reduction and a prolonged remission (AU)


Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Dermatomiosite/diagnóstico , Dermatomiosite/tratamento farmacológico , Imunossupressores/metabolismo , Imunossupressores/farmacocinética , Imunossupressores/uso terapêutico , Ciclofosfamida/uso terapêutico , Debilidade Muscular/complicações , Debilidade Muscular/diagnóstico , Hipertensão/complicações , Hipertensão/diagnóstico , Glucocorticoides/uso terapêutico , Metilprednisolona/uso terapêutico , Fator de Necrose Tumoral alfa/uso terapêutico , Receptores do Fator de Necrose Tumoral/uso terapêutico
19.
Rev. esp. enferm. dig ; 105(1): 3-6, ene. 2013. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-112266

RESUMO

Introducción: la baja prevalencia de las fístulas enterocutáneas (FEC) en los pacientes con enfermedad de Crohn (EC) justifica la escasez de estudios que analicen el efecto del tratamiento médico y la necesidad de cirugía en estos pacientes. El objetivo del presente estudio ha sido evaluar las características clínicas de los pacientes con EC que presentan FEC y la repuesta a los distintos tratamientos. Material y métodos: se analizaron retrospectivamente los pacientes con EC que presentaron FEC desde 1970 a 2009 en tres centros terciarios de España analizando las características clínicas de los pacientes, las respuestas a los tratamientos así como la correlación entre la respuesta a terapias biológicas de la FEC y enfermedad perianal. La actividad inflamatoria de la enfermedad se midió mediante el índice de Harvey-Bradshaw. Las definiciones de respuesta parcial o completa se establecieron a juicio del médico responsable. Resultados: se incluyeron 26 pacientes (18 mujeres), en más de la mitad de los casos (67%) el tratamiento con anti-TNF mejoró el drenaje de la fístula. Las fístulas post-quirúrgicas respondieron mejor al tratamiento con anti-TNF que las fístulas espontáneas (80 vs. 57%). Se obtuvo un 100% y un 60% de cierre en fístulas espontáneas y post-quirúrgicas tras cirugía, respectivamente. Conclusiones: aunque la mayoría de los pacientes requirieron cirugía como tratamiento definitivo, los fármacos anti-TNF mejoraron el débito de la fístula en un porcentaje aceptable de los pacientes tratados, por lo que en un grupo seleccionado podría considerarse una estrategia de tratamiento previo a cirugía(AU)


Introduction: the low prevalence of enterocutaneous fistulas (ECF) in patients with Crohn’s disease (CD) justifies the scarcity of studies that analyze the effect of medical treatment and the need for surgery in these patients. The objective of this study was to evaluate the clinical characteristics of patients with CD who have ECF and the response to different treatments. Material and methods: patients with CD who presented ECF fistula between 1970 and 2009 in three tertiary centers in Spain were analyzed retrospectively for their clinical characteristics, response to treatment as well as the correlation between the response to biological therapies for ECF and perianal disease. The inflammatory activity of the disease was measured using the Harvey-Bradshaw index. The definitions of partial or complete response were based on the treating physician’s judgment. Results: twenty six patients were included (18 women); in more than half of cases (67%), anti-TNF treatment improved fistula drainage. Postoperative fistulas responded better to anti-TNF treatment than did spontaneous fistulas (80 versus 57%). One hundred percent and 60% of spontaneous and postoperative fistulas closed after surgery, respectively. Conclusions: although the majority of patients required surgery as the ultimate treatment, anti-TNF drugs improved fistula output in an acceptable percentage of patients who were treated. Therefore, this may be a treatment strategy prior to surgery in a select group of patients(AU)


Assuntos
Humanos , Masculino , Feminino , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/cirurgia , Fístula/epidemiologia , Fístula/cirurgia , Fístula do Sistema Digestório/terapia , Fator de Necrose Tumoral alfa/uso terapêutico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Colonoscopia , Doença de Crohn/fisiopatologia , Doença de Crohn , Estudos Retrospectivos , Dor Abdominal/diagnóstico , Dor Abdominal/etiologia , Metronidazol/uso terapêutico , Estatísticas não Paramétricas , Imagem por Ressonância Magnética/métodos , Imagem por Ressonância Magnética
20.
Arch. Soc. Esp. Oftalmol ; 88(1): 36-39, ene. 2013. ilus
Artigo em Espanhol | IBECS | ID: ibc-109505

RESUMO

Introducción: En los últimos años se ha registrado un aumento en la incidencia de infección tuberculosa, debido a la utilización cada vez mayor de fármacos inhibidores del factor de necrosis tumoral alfa (anti-TNF alfa) en el tratamiento de enfermedades inflamatorias. Caso clínico: Se describe el caso de un varón en tratamiento con infliximab (anti-TNF alfa) que desarrolla tuberculosis diseminada con afectación ocular. Conclusión: Es de gran importancia la realización de un screening apropiado para detectar pacientes con riesgo de desarrollar tuberculosis antes de iniciar tratamiento con dichos fármacos. Con este propósito, el QuantiFERON®-TB Gold in Tube (Interferon Gamma Release Assay, IGRA) se presenta como una alternativa de alta sensibilidad y especificidad(AU)


Introduction: There has been an increase in the incidence of tuberculosis infection in recent years, due to the increasing use of drugs inhibiting tumour necrosis factor-alpha (anti-TNF alpha) in the treatment of inflammatory diseases. Case report: We report the case of a male patient being treated with infliximab (anti-TNF alpha) who developed disseminated tuberculosis with ocular involvement. Conclusion: It is very important to conduct a proper screening to detect patients at risk for tuberculosis before starting treatment with these drugs. For this purpose, the QuantiFERON®-TB Gold in Tube (Interferon Gamma Release Assay, IGRA) is presented as an alternative screening test with high sensitivity and specificity(AU)


Assuntos
Humanos , Masculino , Adulto , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/uso terapêutico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Tuberculose Ocular/complicações , Tuberculose Ocular/diagnóstico , Tuberculose Ocular/tratamento farmacológico , Granuloma/complicações , Granuloma/diagnóstico , Tomografia de Coerência Óptica/instrumentação , Tomografia de Coerência Óptica/métodos , Tomografia de Coerência Óptica , Granuloma , Angiografia/métodos , Angiografia
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