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2.
Rev. neurol. (Ed. impr.) ; 69(supl.2): S1-S9, 17 dic., 2019.
Artigo em Espanhol | IBECS | ID: ibc-186964

RESUMO

Introducción. La cladribina es un profármaco, análogo sintético de la desoxiadenosina, aprobado como terapia de reconstitución inmune selectiva en la esclerosis múltiple (EM) recurrente muy activa del adulto. Objetivos. Revisar el desarrollo del fármaco, su mecanismo de acción y los datos de eficacia y seguridad obtenidos hasta la fecha, y establecer recomendaciones de manejo por expertos españoles en la práctica clínica. Desarrollo. El tratamiento de la EM se ha simplificado con cladribina comprimidos, y se necesitan dos cursos cortos de administración durante dos años consecutivos (máximo 20 días) para mantener una eficacia de hasta cuatro años tras la primera dosis. Los resultados de los ensayos clínicos han demostrado la seguridad, la tolerabilidad y la eficacia a largo plazo de la cladribina comprimidos en pacientes con EM recurrente. Así, los pacientes tratados con cladribina presentaron una reducción significativa de la tasa de brotes, del riesgo de progresión de la discapacidad y del desarrollo de nuevas lesiones en la resonancia magnética en comparación con los tratados con placebo. En cuanto a la seguridad, los pacientes tratados presentaron una mayor frecuencia de linfopenia, en relación con su mecanismo de acción, y de infecciones por el virus del herpes zóster. Los resultados a largo plazo con ocho años de seguimiento han mostrado que los pacientes tratados no tienen mayor riesgo de desarrollar efectos graves, como neoplasias malignas o infecciones oportunistas. Conclusiones. La cladribina es la primera terapia oral de corta administración que ha demostrado ser eficaz y segura en pacientes con EM recurrente muy activa, y con un efecto sostenido en el tiempo. Las recomendaciones de expertos españoles sobre su manejo suponen un complemento fundamental a las consideraciones descritas por las agencias reguladoras


Introduction: Cladribine is a prodrug, a synthetic analogue of deoxyadenosine, approved for use as selective immune reconstitution therapy in very active recurring multiple sclerosis in adults. Aims: To review the development of the drug, its mechanism of action and the efficacy and safety data obtained to date, as well as to establish recommendations of Spanish experts for its use in clinical practice. Development: The treatment of multiple sclerosis has been simplified with cladribine tablets, and two short courses of administration for two consecutive years (maximum 20 days) are needed to maintain an efficacy of up to four years after the first dose. Results of clinical trials have demonstrated the safety, tolerability and long-term efficacy of cladribine tablets in patients with recurring multiple sclerosis. Thus, patients treated with cladribine presented a significant reduction in the rate of flare-ups, in the risk of disability progression and in the development of new lesions in magnetic resonance imaging compared to those treated with placebo. In terms of safety, the treated patients had a higher frequency of lymphopenia, in relation to its mechanism of action, and of infections by herpes zoster virus. Long-term results with eight years’ follow-up have shown that treated patients are not at greater risk of developing serious events, such as malignant neoplasms or opportunistic infections. Conclusions: Cladribine is the first short-course oral therapy that has been shown to be effective and safe in patients with very active recurring multiple sclerosis, and with a sustained effect over time. The recommendations of Spanish experts on its usage are a fundamental complement to the considerations described by the regulatory agencies


Assuntos
Humanos , Adulto , Cladribina/administração & dosagem , Esclerose Múltipla Recidivante-Remitente/terapia , Reconstituição Imune , Comprimidos/metabolismo , Cladribina/análogos & derivados , Linfócitos/efeitos dos fármacos , Segurança do Paciente
3.
Reumatol. clín. (Barc.) ; 15(6): 363-367, nov.-dic. 2019. tab, graf
Artigo em Inglês | IBECS | ID: ibc-189655

RESUMO

OBJECTIVE: To determine to neutrophil-to-lymphocyte ratio (NLR) in granulomatosis with polyangiitis (GPA) patients and to study its relation to disease manifestations and activity. METHODS: The study included 44 GPA patients and 44 matched age and sex controls. Full history taking, thorough clinical examination with more attention to ocular examination, laboratory and radiological investigations were considered. Disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS). RESULTS: The patients (21 males and 23 females) had a mean age of 45.66+/-7.24 years, disease duration 6.8+/-3.6 years and BVAS 50.1+/-14.3. All patients had a positive cytoplasmic anti-neutrophil cytoplasmic antibody (c-ANCA) while only 5 had a positive p-ANCA. The NLR was significantly increased in the GPA patients (5.1+/-2.4) compared to the control (1.5+/-0.8) (P<.0001). Ten patients with uveitis had a significantly higher NLR (6.5+/-1.9) compared to those without (4.7+/-2.4) (0.03) while those with proptosis (n=10), cutaneous manifestations (n=17) or ischemic heart disease (n=9) had a significantly lower NLR than those without (P=.0001, P=.017 and P=.046 respectively). The NLR did not significantly correlate with any of the patients' characteristics. The NLR inversely yet insignificantly correlated with the disease activity (r=-0.02, P=.93). CONCLUSION: The NLR may have a significant role in the pathogenesis of GPA, the development of uveitis or proptosis, cutaneous manifestations and ischemic heart disease. NLR may serve as a future potential companion to c-ANCA positivity in diagnosing and evaluating GPA and may play a role in the tissue-specific and clinical characteristics


OBJETIVO: Determinar el ratio neutrófilos/linfocitos (RNL) en pacientes con granulomatosis con poliangeítis (GP), y estudiar su relación con las manifestaciones y actividad de la enfermedad. MÉTODOS: El estudio incluyó a 44 pacientes con GP, y 44 controles pareados por edad y sexo. Se consideraron la historia clínica completa, la exploración minuciosa con especial atención al examen ocular, así como las pruebas de laboratorio y radiológicas. La actividad de la enfermedad se evaluó utilizando la clasificación Birmingham Vasculitis Activity Score (BVAS). RESULTADOS: Los pacientes (21 varones y 23 mujeres) tenían una edad media de 45,66+/-7,24 años, duración de la enfermedad de 6,8+/-3,6 años, y BVAS 50,1+/-14,3. Todos los pacientes tenían anticuerpos anticitoplasma de anti-neutrófilos positivos (c-ANCA), y únicamente 5 de ellos tenían p-ANCA positivo. El RNL se vio significativamente incrementado en los pacientes de GP (5,1+/-2,4) en comparación con el grupo control (1,5+/-0,8) (p < 0,0001). En 10 pacientes con uveítis se observó un RNL significativamente superior (6,5+/-1,9) en comparación con aquellos sin uveítis (4,7+/-2,4) (0,03), mientras que en aquellos con proptosis (n=10), manifestaciones cutáneas (n=17) o cardiopatía isquémica (n=9) se observó un RNL significativamente inferior al de aquellos sin dichas manifestaciones (p = 0,0001; p = 0,017 y p = 0,046, respectivamente). El RNL no guardó una correlación significativa con ninguna de las características de los pacientes. Sin embargo, el RNL guardó una correlación no significativa con la actividad de la enfermedad (r=-0,02; p = 0,93). CONCLUSIÓN: El RNL puede desempeñar un papel significativo en la patogenia de la GP, el desarrollo de uveítis o proptosis, manifestaciones cutáneas y cardiopatía isquémica. El RNL puede servir como futuro complemento potencial de la positividad de c-ANCA a la hora de diagnosticar y evaluar la GP, y jugar un papel con relación a sus características tisulares específicas y clínicas


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Granulomatose com Poliangiite/sangue , Linfócitos , Neutrófilos , Granulomatose com Poliangiite/imunologia , Contagem de Leucócitos
4.
Actas urol. esp ; 43(9): 503-508, nov. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-185252

RESUMO

Objetivos: El objetivo del presente estudio es evaluar la correlación entre la puntuación de riesgo de la Organización Europea para la Investigación y Tratamiento del Cáncer (EORTC, por sus siglas en inglés) y el índice neutrófilo/linfocito (INL) en pacientes con cáncer de vejiga no músculo-invasivo, y la relación entre el INL y los grupos de riesgo. Métodos: Se revisaron retrospectivamente los datos de 212 pacientes con cáncer de vejiga no músculo-invasivo incluidos en el estudio. Los tumores se clasificaron de acuerdo con el sistema de la Organización Mundial de la Salud de 1973 y el sistema TNM de estadificación (tumor, ganglio y metástasis) de 2002. Siguiendo las directrices de la Asociación Europea de Urología, se llevó a cabo la estratificación de los pacientes en grupos de bajo, intermedio y alto riesgo para recidiva y progresión. El día previo a la operación se midieron y analizaron los valores séricos del INL para determinar el valor basal de neutrófilos y linfocitos. Resultados: De los 212 pacientes, 193 eran hombres y 19 mujeres. La media de edad fue 66,7. La puntuación media de INL fue de 3,04 ± 2,11. Se encontró una mayoría de tumores T1, tumores G3, tumores múltiples y tumores > 3 cm en pacientes con INL > 2,41. Tras comparar los 3 grupos de riesgo, se obtuvieron tasas de INL significativamente mayores en los pacientes del grupo de alto riesgo (p < 0,001). Al evaluar la correlación entre las puntuaciones de recidiva y progresión del INL y la EORTC, se observó que un valor elevado del INL se asocia a un aumento significativo en la puntuación de recidiva (r = 0,252; p < 0,001) y progresión (r = 0,145; p = 0,034). Conclusiones: Este estudio demostró la asociación entre un INL alto con los tumores T1, de grado alto, tumores múltiples, tumores > 3 cm y con el grupo de alto riesgo EORTC en pacientes con cáncer de vejiga no músculo-invasivo. También hubo una correlación positiva de la recidiva y progresión entre INL y EORTC


Objectives: Aim of this study is to evaluate the correlation between European Organization for Research and Treatment of Cancer (EORTC) risk score and neutrophil-lymphocyte ratio (NLR) in patients with non-muscle invasive bladder cancer and the relationship between NLR and risk groups. Methods: We retrospectively reviewed data of 212 patients with non-muscle invasive bladder cancer were included in the study. The tumors were graded according to the 1973 World Health Organization grading system and the tumor node metastasis (TNM) 2012 staging system. Patients were categorized low, intermediate and high risk for recurrence and progression, according to European Association of Urology guidelines. Serum values for the NLR were measured on the day before the operation to ascertain the baseline value for neutrophil and lymphocyte counts and statistically analyzed. Results: Of the 212 patients, 193 were male and 19 were female. Mean age was 66.7. Mean NLR score was 3.04 ± 2.11. T1 tumors, G3 tumors, multiple tumors and > 3 cm tumors seen mostly in patients with NLR > 2.41. Low, intermediate and high risk groups compared and NLR rates were significantly higher in high risk group patients (P < .001). When the correlation between NLR and EORTC recurrence and progression scores was evaluated, it was observed that as NLR value increased, recurrence (r = 0.252, P < .001) and progression (r = 0.145, P = .034) scores increased significantly. Conclusions: This study demonstrated the association of high NLR value with T1 tumor, high grade, multiple tumor, > 3 cm tumor and EORTC high risk group in non-muscle invasive bladder cancer patients. There was also a positive correlation between NLR and EORTC recurrence and progression scores


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias da Bexiga Urinária/diagnóstico , Neutrófilos/patologia , Linfócitos/patologia , Fatores de Risco , Neoplasias da Bexiga Urinária/patologia , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/patologia , Grupos de Risco , Estudos Retrospectivos , Classificações em Saúde , Razão de Chances , Intervalos de Confiança
5.
Cir. pediátr ; 32(4): 185-189, oct. 2019. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-184107

RESUMO

Introducción. El índice neutrófilo-linfocito (INL) se ha postulado como marcador inflamatorio en distintas patologías abdominales como la apendicitis aguda (AA). Sin embargo, existen pocos estudios que determinen su asociación con el grado de severidad de la AA. Este es el primer estudio que analiza la utilidad del INL como factor predictor de peritonitis en la AA en niños. Material y métodos. Estudio observacional retrospectivo en pacientes intervenidos de AA durante los años 2017 y 2018. Se distribuyeron en dos grupos según el diagnóstico intraoperatorio (AA no complicada y AA con peritonitis). Se analizaron variables demográficas y analíticas. Se definió el INL como el cociente entre los valores absolutos de neutrófilos y linfocitos. Se determinó mediante curvas ROC la sensibilidad y especificidad para el diagnóstico de peritonitis de distintos parámetros analíticos. Resultados. Se incluyeron un total de 398 pacientes (AA no complicada n= 342 y AA con peritonitis n=56), con una edad media de 10,5±2,9 años. El INL presentó un área bajo la curva (AUC) de 0,78, significativamente superior a la determinación de leucocitos (AUC 0,71; p=0,002) y de neutrófilos (AUC 0,74; p=0,009). No se observaron diferencias al compararlo con la determinación de la proteína C reactiva (AUC 0,79; p=0,598). Se estimó el punto de corte de INL>8,75 con una sensibilidad y especificidad de 75,0 y 72,2% respectivamente. Conclusión. El INL se postula como una herramienta útil para predecir la presencia de peritonitis en AA, y podría considerarse una alternativa a otras determinaciones de mayor coste como la proteína C reactiva


Aim of the study. The neutrophilto-lymphocyte ratio (NLR) has been postulated as an inflammatory marker in several abdominal pathologies such as acute appendicitis (AA). However, there are few studies that determine its association with the degree of severity of AA. This is the first study that analyzes the usefulness of NLR as a predictor of peritonitis in children with AA. Methods. Retrospective observational study in patients treated of AA during the years 2017 and 2018. They were divided into two groups according to the intraoperative diagnosis (uncomplicated AA and AA with peritonitis). Demographic and analytical variables were analyzed. The NLR was defined as the quotient between the absolute values of neutrophils and lymphocytes. The sensitivity and specificity for the diagnosis of peritonitis of different analytical parameters were determined by ROC curves. Results. A total of 398 patients were included (uncomplicated AA n=342 and AA with peritonitis n=56), with a mean age of 10.5±2.9 years. The NLR had an area under the curve (AUC) of 0.78, significantly higher than the determination of leukocytes (AUC 0.71, p=0.002) and of neutrophils (AUC 0.74, p=0.009). No differences were observed when compared to the determination of C-reactive protein (AUC 0.79, p=0.598). A cut-off point of NLR>8.75 was estimated with a sensitivity and specificity of 75.0 and 72.2% respectively. Conclusions. The NLR is a useful tool to predict the presence of peritonitis in AA, and could be considered an alternative to other higher cost determinations such as C-reactive protein


Assuntos
Humanos , Masculino , Feminino , Criança , Apendicite/diagnóstico , Peritonite/diagnóstico , Linfócitos/fisiologia , Contagem de Leucócitos/métodos , Valor Preditivo dos Testes , Apendicite/sangue , Índice de Gravidade de Doença , Curva ROC , Estudos Retrospectivos
6.
Arch. bronconeumol. (Ed. impr.) ; 55(9): 472-477, sept. 2019. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-186157

RESUMO

Introducción: La neumonía adquirida en la comunidad (NAC) es una infección frecuente y grave. El objetivo de este trabajo es estudiar la utilidad pronóstica del porcentaje de neutrófilos (NCP) y del cociente neutrófilos/linfocitos (NLR) en pacientes con NAC. Métodos: Estudio retrospectivo de pacientes hospitalizados por NAC con analítica al ingreso y una segunda extracción de control a los 3-5 días. Se consideraron variables desenlace la mortalidad a 30 y 90 días. Resultados: Se incluyó a 209 pacientes. Los pacientes que sobrevivieron redujeron significativamente el NCP y el NLR entre la analítica al diagnóstico y la de control (desde el 85,8 hasta el 65,4% para NCP y de 10,1 a 3,2 para NLR). Fallecieron 25 pacientes en los primeros 90 días. En ellos hubo un menor descenso no significativo para el NCP (del 84,8 al 74,0%) y para NLR (de 9,9 a 6,9). Los valores de NCP y NLR en la analítica de control fueron significativamente mayores en los pacientes fallecidos que en los supervivientes. Aquellos pacientes que presentaron en la analítica de control un NCP superior al 85% o un NLR superior a 10, presentaron un riesgo de mortalidad superior tras ajuste multivariable (HR para NCP 12 y para NLR 6,5). Conclusión: NCP y NLR son parámetros sencillos y de bajo coste, con utilidad pronóstica especialmente al medirse a los 3-5 días del diagnóstico de NAC. Niveles altos de NLR o NCP se asocian con mayor riesgo de mortalidad a los 90 días


Introduction: Community-acquired pneumonia (CAP) is a common serious infection. This study aimed to evaluate the prognostic utility of neutrophil count percentage (NCP) and neutrophil-lymphocyte ratio (NLR) in patients with CAP. Methods: Retrospective study of hospitalized patients with CAP. Patients had a blood test at admission and 3-5 days after hospitalization (early-stage test). The main outcome variables were 30-day and 90-day mortality. Results: Two hundred and 9 patients were included. Patients who survived had significant reductions in both NCP and NLR between admission and the day 3-5 blood tests (from 85.8% to 65.4% for NCP and from 10.1 to 3.2 for NLR). Twenty-five patients died in the first 90 days. Patients who died had lower, non-significant reductions in NCP (from 84.8% to 74%) and NLR (from 9.9 to 6.9) and significantly higher early-stage NCP and NLR than those who survived. NCP values higher than 85% and NLR values higher than 10 in the early-stage blood test were associated with a higher risk of mortality, even after multivariate adjustment (HR for NCP: 12; HR for NLR: 6.5). Conclusion: NCP and NLR are simple, low-cost parameters with prognostic utility, especially when measured 3-5 days after CAP diagnosis. High NLR and/or NCP levels are associated with a greater risk of mortality at 90 days


Assuntos
Humanos , Neutrófilos , Prognóstico , Pneumonia/diagnóstico , Infecções Comunitárias Adquiridas/epidemiologia , Biomarcadores , Linfócitos , Estudos Retrospectivos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Curva ROC , Pneumonia/etiologia , Pneumonia/mortalidade
9.
J. investig. allergol. clin. immunol ; 29(2): 84-93, 2019. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-184050

RESUMO

Eosinophilic asthma is the most common phenotype of severe asthma. It is characterized by abnormal production and release of type 2 cytokines from T helper type 2 (TH2) lymphocytes and type 2 innate lymphoid cells, such as IL-5. This leads to a persistent increase and activation of eosinophils in blood and the airways despite treatment with high-dose inhaled corticosteroids. Eosinophil differentiation, survival, and activation are preferentially regulated by IL-5, a cytokine that binds to the IL-5 receptor (IL-5R), which is located on the surface of eosinophils or basophils and plays a critical role in the pathogenesis and severity of asthma. Benralizumab is a monoclonal antibody that binds to IL-5R via its Fab domain, blocking the binding of IL-5 to its receptor and resulting in inhibition of eosinophil differentiation and maturation in bone marrow. In addition, this antibody is able to bind through its afucosylated Fc domain to the RIIIa region of the Fcgamma receptor on NK cells, macrophages, and neutrophils, thus strongly inducing antibody-dependent, cell-mediated cytotoxicity in both circulating and tissue-resident eosinophils. This double function of benralizumab induces almost complete fast and maintained depletion of eosinophils that is much greater than that induced by other monoclonal antibodies targeting the IL-5 pathway, such as mepolizumab and reslizumab. This review focuses on benralizumab as an alternative to other agents targeting the IL-5 pathway in the treatment of eosinophilic asthma


El asma eosinofílica es el fenotipo más común del asma grave. Se caracteriza por una producción y liberación anómala de citocinas de tipo 2, como la IL-5, por los linfocitos T colaboradores de tipo 2 (Th2) y las células linfoides innatas de tipo 2 (ILC-2). Con ello se activan los eosinófilos y se incrementa su número en sangre y vías respiratorias, a pesar del tratamiento con dosis altas de corticosteroides inhalados. La diferenciación, supervivencia y activación de los eosinófilos está regulada principalmente por la IL-5, una citocina que se une a su receptor (IL-5R), situado en la superficie de eosinófilos y basófilos, y que desempeña un papel fundamental en la patogénesis y gravedad del asma. El benralizumab es un anticuerpo monoclonal que se une al IL-5R a través de su dominio Fab, bloqueando la unión de la IL-5 a su receptor, lo que provoca una inhibición de la diferenciación y maduración de los eosinófilos en la médula ósea. Además, este anticuerpo es capaz de unirse a través de su dominio Fc afucosilado a la región RIIIa del receptor Fcgamma situado en células NK, macrófagos y neutrófilos, induciendo así una intensa citotoxicidad mediada por células dependiente de anticuerpos (ADCC), tanto de los eosinófilos circulantes como de los residentes en tejidos. Esta doble función del benralizumab induce una disminución casi completa de los eosinófilos de una forma rápida y mantenida, mucho mayor a la inducida por otros anticuerpos monoclonales dirigidos contra la IL-5, como el mepolizumab o el reslizumab. Esta revisión se centra en describir el uso del benralizumab en el tratamiento del asma eosinofílica como una alternativa a otros agentes que actúan directamente sobre la IL-5


Assuntos
Humanos , Asma/tratamento farmacológico , Eosinofilia/tratamento farmacológico , Interleucina-5/imunologia , Linfócitos/imunologia , Citocinas/imunologia , Teste de Degranulação Basófila/métodos , Exacerbação dos Sintomas , Asma/imunologia , Eosinofilia/imunologia , Variação Biológica da População/imunologia
12.
Clin. transl. oncol. (Print) ; 20(12): 1548-1556, dic. 2018. tab, graf
Artigo em Inglês | IBECS | ID: ibc-173761

RESUMO

Purpose: Elevated markers of host inflammation, a hallmark of cancer, have been associated with worse outcomes in several solid tumors. Here, we explore the prognostic role of the derived neutrophil-to-lymphocyte ratio (dNLR), across different tumor subtypes, in patients with early breast cancer. Patients and methods: This was a retrospective analysis of 1246 patients with lymph node-positive, operable early breast cancer enrolled in the GEICAM/9906 trial, a multicenter randomized phase 3 study evaluating adjuvant chemotherapy. dNLR was calculated as the ratio of neutrophils and the difference between total leukocytes and neutrophils in peripheral blood before chemotherapy. Disease-free survival (DFS) and overall survival were explored using a Cox proportional hazard analysis. Results: The analysis comprised 1243 (99.8%) patients with dNLR data, with a median follow-up of 10 years. Data on intrinsic subtypes were available from 818 (66%) patients (luminal A 34%, luminal B 32%, HER2-enriched 21% and basal-like 9%). Median dNLR was 1.35 [interquartile range (IQR) 1.08-1.71]. In the whole population, dNLR was not prognostic after adjustment for clinico-pathological factors. However, dNLR ≥ 1.35 was independently associated with worse DFS in the hormone receptor-negative/HER2+ population (HR 2.86; p = 0.038) and in patients with one to three lymph node metastases (HR 1.32, p = 0.032). There was a non-significant association with worse DFS in non-luminal and in HER2-enriched tumors (HR 1.40, p = 0.085 and HR 1.53, p = 0.067). No significant interaction was observed between the treatment arm and dNLR. Conclusion: Elevated dNLR appears to be an adverse prognostic factor in hormone receptor-negative early breast cancer


No disponible


Assuntos
Humanos , Feminino , Neoplasias da Mama/patologia , Neutrófilos , Linfócitos , Inflamação/fisiopatologia , Metástase Linfática/patologia , Estudos Retrospectivos , Neoplasias da Mama/classificação , Prognóstico , Taxa de Sobrevida , Mediadores da Inflamação/análise , Fatores de Risco
13.
Clin. transl. oncol. (Print) ; 20(9): 1219-1225, sept. 2018. tab, graf
Artigo em Inglês | IBECS | ID: ibc-173708

RESUMO

Purpose: The aim of this study was to determine whether different radiotherapy (RT) fractionation schemes induce disparate effects on lymphocyte and its subsets in breast cancer patients. Methods: 60 female patients diagnosed with breast cancer were recruited in this study after receiving modified radical mastectomy and were randomly divided into two groups. One group received irradiation at a standard dose of 50 Gy in 25 fractions and the other at a dose of 40.3 Gy in 13 fractions. Both total lymphocyte count and its composition were recorded at three timepoints: right before the radiation treatment (T0), immediately after the last fraction of radiotherapy (T1) and 6 months after irradiation therapy ended (T2). Results: Both groups experienced temporal lymphopenia after finishing local radiation (T1) (13F T0 vs. T1 1570.6 ± 243.9 vs. 940.6 ± 141.8, **p < 0.01; 25F T0 vs. T1 1620.5 ± 280.2 vs. 948.5 ± 274.6, **p < 0.01), while the lymphocyte count recovered at follow-up time (T2), and the cell count in the hypofractionation group (13F) was higher than the standard fraction group (25F) (13F vs. 25F 1725.6 ± 225.6 vs. 1657.5 ± 242.4, *p < 0.05). With respect to the composition of lymphocyte, we found T cell, B cell, and NK cell reacted differently to different radiotherapy protocols. Conclusions: Different RT protocols impose different impacts on immunity, leading us to further explore the optimal radiotherapy regimes to synergy with immunotherapy


No disponible


Assuntos
Humanos , Feminino , Neoplasias da Mama/radioterapia , Linfócitos/efeitos da radiação , Subpopulações de Linfócitos/efeitos da radiação , Radioterapia/métodos , Neoplasias da Mama/sangue , Antígeno CTLA-4/efeitos da radiação , Fracionamento da Dose de Radiação
14.
An. pediatr. (2003. Ed. impr.) ; 88(6): 315-321, jun. 2018. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-176955

RESUMO

Introducción: La bronquiolitis aguda (BA) del lactante tiene una evolución grave entre el 6 y el 16% de los casos ingresados. Su patogenia y evolución está relacionada con la respuesta de los linfocitos T. El objetivo del presente estudio es comprobar si la menor respuesta linfocitaria sistémica está relacionada con una peor evolución de la BA en lactantes ingresados. Pacientes y método: Estudio observacional-analítico retrospectivo de casos-controles anidados en una cohorte de ingresados por BA-VRS en el periodo de octubre del 2010 a marzo del 2015. Se incluyó a aquellos con hemograma en las primeras 48 h de dificultad respiratoria. Se excluyó a los lactantes con patología de base, sobreinfección bacteriana y prematuros ≤ 32 semanas de gestación. La variable principal dicotómica fue ingreso UCIP. Otras variables fueron: sexo, edad, edad posmenstrual, exposición gestacional y posnatal al tabaco, mes de ingreso, tipo de lactancia y días de evolución del distrés respiratorio. Las cifras de linfocitos fueron categorizadas por cuartiles. Se realizó un análisis bivariante con la variable principal y posteriormente regresión logística para analizar factores de confusión. Resultados: El estudio incluyó a 252 lactantes. El 6,6% (17) precisó UCIP. La diferencia de media ± DE de linfocitos para pacientes ingresados y no ingresados en UCIP fue de 4.044 ± 1.755 y 5.035 ± 1.786, respectivamente (t de Student, p < 0,05). Se encontró asociación entre ingreso UCIP y la cifra de linfocitos < 3.700/ml (Chicuadrado p=0,019; OR: 3,2), que se mantuvo en la regresión logística con independencia de la edad y del resto de factores estudiados (Wald 4,191 p = 0,041; OR: 3,8). Conclusiones: Existe relación entre la linfocitosis < 3.700/ml en los primeros días de la dificultad respiratoria y una peor evolución en lactantes < 12 meses previamente sanos y edad gestacional mayor de 32 semanas con BA-VRS


Introduction: Acute bronchiolitis (AB) of the infant has a serious outcome in 6-16% of the hospital admitted cases. Its pathogenesis and evolution is related to the response of the T lymphocytes. The objective of the present study is to determine if the lower systemic lymphocytic response is related to a worse outcome of AB in hospitalised infants. Patients and method: Retrospective observational-analytical study of cases-controls nested in a cohort of patients admitted due to RSV-AB between the period from October 2010 to March 2015. Those with a full blood count in the first 48hours of respiratory distress were included. Infants with underlying disease, bacterial superinfection, and premature infants < 32 weeks of gestation were excluded. The main dichotomous variable was PICU admission. Other variables were: gender, age, post-menstrual age, gestational and post-natal tobacco exposure, admission month, type of lactation, and days of onset of respiratory distress. Lymphocyte counts were categorised by quartiles. Bivariate analysis was performed with the main variable and then by logistic regression to analyse confounding factors. Results: The study included 252 infants, of whom 6.6% (17) required PICU admission. The difference in mean ± SD of lymphocytes for patients admitted to and not admitted to PICU was 4,044 ± 1755 and 5,035 ± 1786, respectively (Student-t test, P < .05). An association was found between PICU admission and lymphocyte count < 3700/ml (Chi-squared, P = .019; OR: 3.2) and it was found to be maintained in the logistic regression, regardless of age and all other studied factors (Wald 4.191 P = .041, OR: 3.8). Conclusions: A relationship was found between lymphocytosis < 3700/ml in the first days of respiratory distress and a worse outcome in previously healthy infants < 12 months and gestational age greater than 32 weeks with RSV-AB


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Bronquiolite/imunologia , Bronquiolite/virologia , Estudos de Casos e Controles , Imunidade Celular , Linfócitos/fisiologia , Vírus Sincicial Respiratório Humano , Infecções por Vírus Respiratório Sincicial/imunologia , Estudo Observacional , Doença Aguda , Estudos de Coortes , Estudos Retrospectivos , Índice de Gravidade de Doença
15.
Clin. transl. oncol. (Print) ; 20(4): 476-483, abr. 2018. tab, graf
Artigo em Inglês | IBECS | ID: ibc-171640

RESUMO

Background. Nowadays, neoadjuvant chemotherapy (nCT) in breast cancer is more and more standardized, not only in advanced tumours but also in those for which there is an attempt to achieve breast-conserving surgery. In literature, we can find evidences of the relationship between several types of tumours and systemic inflammatory response. Our objective is to analyse the prognostic value of blood parameters (lymphocytes, neutrophils, monocytes, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-monocyte ratio (NMR) and neutrophil-to-lymphocyte ratio (NLR) in breast cancer (BC) patients treated with nCT. Methods. A retrospective cohort of 150 breast cancer patients treated with nCT and subsequently with surgery was analysed. Data about the patients, histology, response to chemotherapy and peripheral blood values of lymphocytes, monocytes and neutrophils was collected, and used to calculate the LMR, NMR and NLR. Univariate and multivariate analyses were performed for the variables to see the relationship of the ratios to disease-free survival (DFS) and overall survival (OS). Results. Patients with high LMR (≥5.46) and low NLR (<3.33) were associated with a lower percentage of relapse (P = 0.048 and P = 0.015, respectively) and, above all, NLR was associated with a better survival (P = 0.024), being those factors that predict a good progress. Conclusion. High LMR and low NLR can be considered as favourable prognostic factors in BC patients treated with nCT (AU)


No disponible


Assuntos
Humanos , Feminino , Neoplasias da Mama/patologia , Antineoplásicos/farmacocinética , Linfócitos , Monócitos , Neutrófilos , Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante/estatística & dados numéricos , Estudos Retrospectivos , Biomarcadores Tumorais/análise , Prognóstico
18.
Rev. esp. patol ; 50(3): 174-178, jul.-sept. 2017. ilus
Artigo em Espanhol | IBECS | ID: ibc-163527

RESUMO

El carcinoma gástrico tipo linfoepitelioma es una entidad poco frecuente y mal caracterizada. Históricamente no se ha considerado una entidad como tal y frecuentemente se ha utilizado como sinónimo del carcinoma medular y del carcinoma gástrico convencional con estroma linfoide. Diferenciar esta entidad tiene mucha relevancia tanto clínica como pronóstica. Se describe un caso de un hombre de 77 años con una lesión ulcerada en fundus. El examen histológico reveló unas estructuras neoplásicas glandulares acompañadas de un marcado estroma linfoide. Dicha lesión presentó intensa expresión del virus de Epstein-Barr, expresión de las proteínas reparadoras del ADN y una distribución característica de las poblaciones linfoides. El objetivo de este estudio es definir criterios útiles que permitan distinguir esta inusual lesión y estudiar el inmunofenotipo de las poblaciones linfoides (AU9


Gastric lymphoepithelioma-like carcinoma is a rare and poorly characterized condition which historically has not been considered a specific entity, usually being considered synonymous with medullary carcinoma and conventional gastric carcinoma with lymphoid stroma. However, the differentiation of this entity is of clinical and prognostic importance. We report a case of a 77 year old man who presented with a gastric ulcer in the fundus. Histological examination revealed the presence of neoplastic glandular structures with marked lymphoid stroma. The immunohistochemical staining showed strong expression for Epstein-Barr virus and DNA repair proteins with a distinctive lymphoid cell distribution. The aim of our study is to determine criteria useful in the recognition of this unusual condition and assess the inmunophenotype of the lymphoid population (AU)


Assuntos
Humanos , Masculino , Idoso , Carcinoma/patologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Linfócitos/patologia , Antígenos Nucleares do Vírus Epstein-Barr/análise , Infecções por Vírus Epstein-Barr/patologia , Perda de Peso , Endoscopia , Patologia/métodos , Imuno-Histoquímica , Adenocarcinoma/patologia
19.
Clin. transl. oncol. (Print) ; 19(8): 1010-1017, ago. 2017. tab, `bgraf, ilus
Artigo em Inglês | IBECS | ID: ibc-164679

RESUMO

Introduction/purpose. BRG1 is a key regulator of leukemia stem cells. Indeed, it has been observed that this type of cells is unable to divide, survive and develop new tumors when BRG1 is down-regulated. Materials and methods. We assessed BRG1 and miR-155 expression in 23 leukemia cell lines, and two no pathological lymphocyte samples using qPCR. MiR-155 transfection and western blot were used to analyze the relationship between miR-155 and its validated target, BRG1, by measuring protein expression levels. The effect of miR-155 on cell proliferation and prednisolone sensitivity were studied with resazurin assay. Results. BRG1 expression levels could correlate negatively with miR-155 expression levels, at least in Burkitt’s lymphoma and diffuse large B cell lymphoma (DLBCL) cell lines. To clarify the role of miR-155 in the regulation of BRG1 expression, we administrated miR-155 mimics in different leukemia/lymphoma cell lines. Our results suggest that miR-155 regulate negatively and significantly the BRG1 expression at least in the MOLT4 cell line. Conclusion. Our study revealed a previously unknown miR-155 heterogeneity that could result in differences in the treatment with miRNAs in our attempt to inhibit BRG1. However, the expression levels of BRG1 and miR-155, before prednisolone treatment were not statistically significantly associated prednisolone sensitive leukemia cells (AU)


No disponible


Assuntos
Humanos , Linhagem Celular Tumoral , MicroRNAs/análise , Prednisolona/uso terapêutico , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/genética , Linfócitos/citologia , Linfócitos/patologia , Linfoma/diagnóstico , Leucemia/diagnóstico , Reação em Cadeia da Polimerase/métodos , Linhagem Celular/citologia , Linhagem Celular/patologia , Western Blotting
20.
Clin. transl. oncol. (Print) ; 19(6): 711-717, jun. 2017. tab, graf
Artigo em Inglês | IBECS | ID: ibc-162828

RESUMO

Purpose. Many studies recently focus on complicated and expensive genomic tests, but the prognostic values of biochemical markers which are easily obtained in clinics are largely overlooked and without further exploration. This study assesses the association of neutrophil-lymphocyte-ratio (NLR) with prognosis of lung cancer patients. Methods. In 1032 patients with histologically confirmed lung cancer, the association of pretreatment NLR values with overall survival (OS) was evaluated using a Cox proportional hazards model and the temporal relationship of longitudinal NLR was assessed using a mixed effects model. Results. Compared to the patients with a low pretreatment NLR value, those with elevated NLR exhibited a statistically significant worse OS with a hazard ratio (HR) of 1.50 (P < 0.0001) after adjusting for age, gender, race, smoking status, drinking status, tumor stage, tumor grade, histology, and treatments. A significant trend of increasing HRs along with increasing NLR values was observed. The increased risk of death conferred by pretreatment NLR values reached a peak level around 2 years after diagnosis. Moreover, in longitudinal analysis, we observed a trend of dramatically increased NLR values in patients who died during follow-up, but stable NLR values in those who were still alive, with a significant interaction of death-alive status with follow-up time (P < 0.0001). Conclusions. Elevated NLR is a potential biomarker to identify lung cancer patients with poor prognosis and should be validated in a future clinical trial (AU)


No disponible


Assuntos
Humanos , Neutrófilos/patologia , Linfócitos , Biomarcadores Tumorais/sangue , Neoplasias Pulmonares/diagnóstico , Biomarcadores Tumorais/administração & dosagem , Prognóstico , Análise Estatística , Estimativa de Kaplan-Meier
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