RESUMEN
Introducción: El objetivo del presente estudio fue realizar un estudio de pruebas diagnósticas entre la escala PRISM III vs la escala PELOD para predecir mortalidad en pacientes que ingresan a la Unidad de Cuidados Intensivos (UCIP) del Hospital Pediátrico Baca Ortiz en el periodo de junio-diciembre 2019. Métodos: En el presente estudio observacional, retrospectivo, se registró la mortalidad y las variables que conforman cada una de las escalas predictivas. Se aplicó estadística descriptiva e inferencial, cálculo del área bajo la curva de ROC. La calibración, se calculó usando el chi2 de Hosmer Lemeshow y la tasa de mortalidad estandarizada mediante le paquete estadístico STATA v16. Resultados: Ingresaron al estudio 150 pacientes. 99 pacientes (66%) fueron hombres, tuvieron una media de edad de 3 años (P25 a P75) de 1 mes a 14 años. La patología de ingreso más frecuente fue la enfermedad posquirúrgica en 43 pacientes (28.6%), y la insuficiencia respiratoria en 31 pacientes (21.6%). La mortalidad fue 12.7%, con una media de estancia hospitalaria de 5 días (1 a 60). La escala de PRIMS III con área bajo la curva de 0.80 (IC 95% de 0.70 a 0.90), sensibilidad 79 % y especificidad 63 % con un puntaje PRISM III de 13 puntos. La escala de PELOD con área bajo la curva de 0.7 (IC 95% de 0.5 a 0.80), sensibilidad de 79 % y especificidad de 60 % con un puntaje PELOD de 21 puntos. Conclusiones: La escala de PRISM III predice la mortalidad mejor que la escala PELOD en este grupo de pacientes pediátricos en las primeras 24 horas.
Introduction: The aim of the present study was a study of diagnostic tests between the PRISM III scale vs the PELOD scale to predict mortality in patients admitted to the Intensive Care Unit (PICU) of the Baca Ortiz Pediatric Hospital in the period of June-December 2019. Methods: In this retrospective, observational study, mortality and the variables that make up each of the predictive scales were recorded. Descriptive and inferential statistics were ap-plied, calculation of the area under the ROC curve. The calibration was calculated using the Hosmer Lemeshow chi2 and the mortality rate standardized using the statistical package STATA v16. Results: 150 patients entered the study. 99 patients (66%) were men, had a mean age of 3 years (P25 to P75) from 1 month to 14 years. The most frequent admission pathology was postoperative disease in 43 patients (28.6%), and respiratory failure in 31 patients (21.6%). Mortality was 12.7%, with a mean hospital stay of 5 days (1 to 60). The PRIMS III scale with area under the curve of 0.80 (95% CI from 0.70 to 0.90), sensitivity 79% and specificity 63% with a PRISM III score of 13 points. The PELOD scale with area under the curve of 0.7 (95% CI from 0.5 to 0.80), sensitivity of 79% and specificity of 60% with a PELOD score of 21 points. Conclusions: the PRISM III scale predicts mortality better than the PELOD scale in this group of pediatric patients in the first 24 hours.
introdução: O objetivo do presente estudo foi realizar um estudo de testes diagnósticos entre a escala PRISM III vs a escala PELOD para predizer mortalidade em pacientes internados na Unidade de Terapia Intensiva (UTIP) do Hospital Pediátrico Baca Ortiz no período de junho a dezembro 2019. Métodos: Nesse estudo retrospectivo e observacional, foram registradas a mortalidade e as variáveis ââque compõem cada uma das escalas preditivas. Foi aplicada estatística descritiva e inferencial, cálculo da área sob a curva ROC. A calibração foi calculada usando o Hosmer Lemeshow chi2 e a taxa de mortalidade padronizada usando o pacote estatístico STATA v16. Resultados: 150 pacientes entraram no estudo. 99 pacientes (66%) eram homens, com idade média de 3 anos (P25 a P75) de 1 mês a 14 anos. A patologia de admissão mais frequente foi doença pós-operatória em 43 pacientes (28,6%) e insuficiência respiratória em 31 pacientes (21,6%). A mortalidade foi de 12,7%, com tempo médio de internação de 5 dias (1 a 60). Escala PRIMS III com área sob a curva de 0,80 (IC 95% de 0,70 a 0,90), sensibilidade 79% e especificidade 63% com escore PRISM III de 13 pontos. A escala PELOD com área sob a curva de 0,7 (IC 95% de 0,5 a 0,80), sensibilidade de 79% e especificidade de 60% com escore PELOD de 21 pontos. Conclusões: A escala PRISM III prediz mortalidade melhor do que a escala PELOD neste grupo de pacientes pediátricos nas primeiras 24 horas.
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Humanos , Preescolar , Niño , Pronóstico , Causas de Muerte , Cuidados Críticos , Mortalidad del Niño , NiñoRESUMEN
Introducción:El síndrome hemofagocítico (SHF) es reconocido como un conjunto de signos clínicos y hallazgos laboratoriales que tienen un grave compromiso en la salud y vitalidad de los niños con una incidencia de 1.2 casos/millón/año. Puede pasar subdiagnosticado y confundido con sepsis de foco inespecífico Caso clínico:Niño de 4 años de edad, sin antecedentes de importancia. Ingresado desde el servicio de emergencia por presentar 20 días de fiebre y dolor abdominal. Requirió intubación por franca falla respiratoria y el ingreso a la Unidad de Cuidados Intensivos Pediátricos. Con hipotensión e insuficiencia hepática, pancitopeniay esplenomegalia. Evolución: Se descartaron infecciones bacterianas con policultivos, SARS-Cov 2negativo,se descartaron inmunodeficiencias congénitas y adquiridas.TORCHnegativo, VDRL no reactivo.La prueba de Epstein Barr fue positivo para IgM.Se determinó endocarditis con derrame pericárdico global. Estudio de biopsia medular normocromía, normocitosis, pancitopenia y blastos <5%, sin infiltración tumoral. Se estableció el Diagnóstico de SHFse inicióciclosporina y corticoterapia.Requirió ventilación mecánica por 20 días con período de pronación de 36 horas. Fue dado de alta a pediatríay posteriormente a domicilio, para control por consulta externa. Conclusión: El diagnóstico del SHF es inusual y subestimado al momento de la evaluación clínica. En el presente reporte se asocia a la presencia del Virus Epstein Barr
Introduction: Hemophagocytic syndrome (HPS) is recognized as a set of clinical signs and laboratory findings that have a serious compromise on the health and vitality of children with an incidence of 1.2 cases / million / year. It can be underdiagnosed and confused with sepsis with a non-specific focus. Clinical case: 4-year-old boy, with no significant history. Admitted from the emergency service due to 20 days of fever and abdominal pain. She required intubation due to frank respiratory failureand admission to the Pediatric Intensive Care Unit. With hypotension and liver failure, pancytopenia and splenomegaly. Evolution: Bacterial infections were ruled out with polycultures, SARS-Cov 2 negative, congenital and acquired immunodeficiencies were ruled out. Negative TORCH, non-reactive VDRL. The Epstein Barr test was positive for IgM. Endocarditis with global pericardial effusion was determined. Medullary biopsy study normochromia, normocytosis, pancytopenia, and blasts <5%, without tumor infiltration. The diagnosis of SHF was established, cyclosporine and corticosteroid therapy were started. He required mechanical ventilation for 20 days with a 36-hour pronation period. He was discharged to pediatrics and later at home, for outpatient control. Conclusion: The diagnosis of HHS is unusual and underestimated at the time of clinical evaluation. In this report it is associated with the presence of the Epstein Barr Virus
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Humanos , Herpesvirus Humano 4 , Infecciones por Virus de Epstein-Barr , Linfohistiocitosis Hemofagocítica , Informes de Casos , PerforinaRESUMEN
Vascular patterning depends on precisely coordinated timing of endothelial cell differentiation and onset of cardiac function. Endoglin is a transmembrane receptor for members of the TGF-beta superfamily that is expressed on endothelial cells from early embryonic gestation to adult life. Heterozygous loss of function mutations in human ENDOGLIN cause Hereditary Hemorrhagic Telangiectasia Type 1, a vascular disorder characterized by arteriovenous malformations that lead to hemorrhage and stroke. Endoglin null mice die in embryogenesis with numerous lesions in the cardiovascular tree including incomplete yolk sac vessel branching and remodeling, vessel dilation, hemorrhage and abnormal cardiac morphogenesis. Since defects in multiple cardiovascular tissues confound interpretations of these observations, we performed in vivo chimeric rescue analysis using Endoglin null embryonic stem cells. We demonstrate that Endoglin is required cell autonomously for endocardial to mesenchymal transition during formation of the endocardial cushions. Endoglin null cells contribute widely to endothelium in chimeric embryos rescued from cardiac development defects, indicating that Endoglin is dispensable for angiogenesis and vascular remodeling in the midgestation embryo, but is required for early patterning of the heart.
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Embrión de Mamíferos , Endocardio , Corazón , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neovascularización Fisiológica , Telangiectasia Hemorrágica Hereditaria/genética , Animales , Tipificación del Cuerpo/fisiología , Diferenciación Celular/fisiología , Quimera/anatomía & histología , Quimera/fisiología , Embrión de Mamíferos/anatomía & histología , Embrión de Mamíferos/fisiología , Endocardio/citología , Endocardio/embriología , Endoglina , Células Endoteliales/citología , Células Endoteliales/fisiología , Regulación del Desarrollo de la Expresión Génica , Corazón/anatomía & histología , Corazón/embriología , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Ratones , Ratones Noqueados , Neovascularización Fisiológica/genética , Neovascularización Fisiológica/fisiologíaRESUMEN
The innate ability of B lymphoma cells to escape control by tumor-reactive T cells must be overcome to develop effective immunotherapies for these diseases. Because signals from both the innate and adaptive immune systems direct the acquisition of strong immunogenicity by professional APCs, the effects of IL-2 and the TLR-7 agonist, S28690, on the immunogenic properties of chronic lymphocytic leukemia (CLL) B cells were studied. IL-2 with S28690 caused CLL cells to proliferate and increased their expression of B7-family members, production of TNF-alpha and IL-10, and levels of tyrosine-phosphorylated STAT-1 and STAT-3 proteins. S28690 increased CD25 expression on CLL cells and sensitized them to IL-2 signaling. However, IL-2 did not change TLR-7 expression or signaling in CLL cells. The ability to stimulate T cell proliferation required additional activation of protein kinase C, which inhibited tumor cell proliferation, "switched off" IL-10 production, and caused essentially all CLL cells (regardless of clinical stage) to acquire a CD83(high)CD80(high)CD86(high)CD54(high) surface phenotype marked by the activation of STAT-1 without STAT-3. These findings suggest that TLR-7 "licenses" human B cells to respond to cytokines of the adaptive immune system (such as IL-2) and provide a strategy to increase the immunogenicity of lymphoma cells for therapeutic purposes.
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Interleucina-2/inmunología , Linfoma de Células B/inmunología , Linfoma de Células B/metabolismo , Transducción de Señal , Receptor Toll-Like 7/inmunología , Receptor Toll-Like 7/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Células Cultivadas , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Imidazoles/farmacología , Leucemia Linfocítica Crónica de Células B/inmunología , Leucemia Linfocítica Crónica de Células B/metabolismo , Linfoma de Células B/patología , Masculino , Persona de Mediana Edad , Fenotipo , Proteína Quinasa C/metabolismo , Quinolinas/farmacología , Receptores de Interleucina-2/genética , Factor de Transcripción STAT1/metabolismo , Factor de Transcripción STAT3/metabolismoRESUMEN
The identification of clinically relevant, active immunomodulatory agents is important for developing immunotherapeutic approaches to chronic lymphocytic leukemia (CLL) and other B-cell lymphomas that are not curable with conventional chemotherapy. In this investigation, the imidazoquinoline Toll-like receptor (TLR)-7/8 agonist, imiquimod, was found to mediate the clearance of a lymphomatous skin lesion in a CLL patient. Imidazoquinolines also activated TLR-7/8 signaling pathways, resulting in increased expression of costimulatory molecules on circulating tumor cells. These observations extend the therapeutic spectrum of imiquimod to cutaneous B-cell lymphomas and suggest the use of TLR-7/8 agonists in CLL immunotherapy.
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Aminoquinolinas/uso terapéutico , Antineoplásicos/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Linfoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Receptor Toll-Like 7/agonistas , Receptor Toll-Like 8/agonistas , Anciano , Progresión de la Enfermedad , Humanos , Imiquimod , Inmunoterapia/métodos , Leucemia Linfocítica Crónica de Células B/patología , Linfoma/patología , Masculino , Transducción de Señal , Neoplasias Cutáneas/patología , Resultado del TratamientoRESUMEN
Based on their activity in patients with advanced stage chronic lymphocytic leukemia (CLL), a phase I/II study was designed to evaluate the feasibility, safety, and efficacy of autologous vaccines made from oxidized tumor cells in patients with earlier stage CLL, and to determine an optimal schedule of injections. Eighteen patients (at risk for disease progression and with white blood cell counts between 15 and 100 x 10(6) cells/ml) were injected intramuscularly with 10 ml of oxidized autologous blood (composed mainly of CLL cells) either 12 times over 6 weeks (group 1), 12 times over 16 days (group 2), or 4 times over 6 weeks (group 3). Fourteen out of eighteen patients had Rai stage 0-II disease, while 4/18 had stage III-IV disease but did not require conventional treatment. Partial clinical responses, associated with enhanced anti-tumor T cell activity in vitro, were observed in 5/18 patients of whom three were in group 2. Stable disease was observed in six patients while disease progression appeared not to be affected in the remaining patients. Toxicity was minimal. Vaccination with oxidized autologous tumor cells appears worthy of further investigation and may be a potential alternative to a "watch and wait" strategy for selected CLL patients.
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Vacunas contra el Cáncer/uso terapéutico , Inmunoterapia , Leucemia Linfocítica Crónica de Células B/inmunología , Leucemia Linfocítica Crónica de Células B/terapia , Linfocitos T/inmunología , Adulto , Anciano , Antígenos CD/inmunología , Antígenos CD/metabolismo , Antígeno B7-1/inmunología , Antígeno B7-1/metabolismo , Antígeno B7-2 , Estudios de Factibilidad , Femenino , Humanos , Masculino , Glicoproteínas de Membrana/inmunología , Glicoproteínas de Membrana/metabolismo , Persona de Mediana Edad , Linfocitos T Citotóxicos/inmunología , Trasplante Autólogo , Células Tumorales CultivadasRESUMEN
Since the intrinsically poor immunogenicity of chronic lymphocytic leukemia (CLL) cells might be a key factor in allowing them to avoid immune control mechanisms, the development of methods to enhance CLL cell immunogenicity might lead to improved disease control. The ability of CLL cells to stimulate T cells was increased significantly by the protein kinase C (PKC) agonist phorbol myristic acetate (PMA). However, under serum-free conditions, PMA-activated CLL cells died within 48 hours. Antioxidants, such as 2-mercaptoethanol (2-ME), or fetal calf serum could prevent the death of these cells but caused them to enter distinct states of differentiation. In the presence of 2-ME, PMA-activated CLL cells extended dendritic-like protrusions and exhibited increased T-cell stimulatory capacity. In the presence of serum, PMA-activated CLL cells developed fewer dendrites, made less IL-10 and more IL-12 p40 mRNA transcripts, and showed an increased capacity to induce IFN-gamma production by T cells. The effects of serum on the promotion of type 1 immune responses by phorbol ester-activated CLL cells were dominant and correlated with activation of the NF-kappaB signaling pathway. Other PKC agonists, such as Bryostatin-1 and a synthetic Bryostatin analog (Picolog), had similar effects on CLL cells. The observation that CLL cells can acquire features of dendritic cells that promote type 1 immunity may find clinical application in immunotherapeutic strategies for this disease.
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Antioxidantes/farmacología , Leucemia Linfocítica Crónica de Células B/inmunología , Proteína Quinasa C/metabolismo , Suero/fisiología , Adulto , Anciano , Presentación de Antígeno/inmunología , Antígenos CD/metabolismo , Antígenos Virales/inmunología , Brioestatinas , Muerte Celular/efectos de los fármacos , Forma de la Célula/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Técnicas de Cocultivo , Medio de Cultivo Libre de Suero/farmacología , Activadores de Enzimas/farmacología , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Proteínas I-kappa B/metabolismo , Inmunofenotipificación , Interferón gamma/metabolismo , Interleucina-10/metabolismo , Interleucina-12/metabolismo , Leucemia Linfocítica Crónica de Células B/metabolismo , Leucemia Linfocítica Crónica de Células B/patología , Activación de Linfocitos/inmunología , Macrólidos/farmacología , Masculino , Mercaptoetanol/farmacología , Persona de Mediana Edad , FN-kappa B/metabolismo , Fosforilación/efectos de los fármacos , Linfocitos T/inmunología , Linfocitos T/metabolismo , Acetato de Tetradecanoilforbol/farmacología , Células Tumorales Cultivadas , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Weak immunogenicity of chronic lymphocytic leukaemia (CLL) cells may contribute to disease progression and inhibit the effectiveness of immunotherapies, such as vaccines. Agents that can enhance the antigen presenting capabilities of CLL cells might then help to improve the clinical results of immunotherapies. This study investigated the effects of the common gamma chain-binding cytokines, interleukin (IL)-2 and IL-15, on costimulatory properties of primary CLL cells from 51 patients. IL-2 improved the ability of CLL cells to stimulate T cell proliferation and increased the expression of costimulatory molecules (particularly CD80) in a dose-dependent fashion, especially in CLL cells with weak expression of CD38. CD80 and CD86 induction by IL-2 were positively regulated through the mitogen-activated protein kinase pathway, while CD86 expression was negatively regulated through Janus kinase pathways. However, further activation with protein kinase C agonists was required for IL-2 activated CLL cells to stimulate autologous T cells sufficiently to clear bystander CLL cells from mixed lymphocyte responses. IL-15 had similar effects on the costimulatory properties of CLL cells. These results suggest a role for IL-2, or IL-15, in immunotherapeutic strategies for CLL.
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Células Presentadoras de Antígenos/inmunología , Antígeno B7-1/inmunología , Inmunoterapia Activa/métodos , Interleucinas/uso terapéutico , Leucemia Linfocítica Crónica de Células B/terapia , Receptores de Interleucina/metabolismo , ADP-Ribosil Ciclasa/inmunología , ADP-Ribosil Ciclasa 1 , Antígenos CD/inmunología , Linfocitos B/inmunología , Antígeno B7-2 , Proliferación Celular , Pruebas Inmunológicas de Citotoxicidad , Relación Dosis-Respuesta Inmunológica , Femenino , Citometría de Flujo , Humanos , Interleucina-15/uso terapéutico , Interleucina-2/uso terapéutico , Subunidad beta del Receptor de Interleucina-2 , Leucemia Linfocítica Crónica de Células B/inmunología , Activación de Linfocitos , Masculino , Glicoproteínas de Membrana/inmunología , Persona de Mediana EdadRESUMEN
PURPOSE: Tumor-reactive T cells were measured in patients with chronic lymphocytic leukemia (CLL) because vaccines that increase the activity of these cells might lead to better disease control. EXPERIMENTAL DESIGN: Proliferation and ELISPOT assays (for T cells producing IFN-gamma after stimulation by CD40-activated CLL cells) were used to determine the prevalence of tumor-reactive T cells in 25 CLL patients at various stages of disease progression. The effects of vaccines, composed of autologous-oxidized tumor cells, on both the clinical course and tumor-reactive T-cell numbers were then determined in 2 patients. RESULTS: CLL-reactive T cells were found at frequencies of > or =10(-3) in 6 of 11 patients. Significant proliferation was found in 15 of 25 patients and correlated with clinical stage. The inability to measure CLL-reactive T cells in the remaining patients was not uniformly a result of generalized T-cell dysfunction or defective antigen presentation by CD40-activated CLL cells. CLL-reactive T-cell frequencies increased in response to vaccination with oxidized autologous tumor cells in a patient with preexisting CLL-reactive T cells but not in a patient where tumor-reactive T cells were undetectable in the ELISPOT assay. CONCLUSIONS: Tumor-reactive T cells exist in some CLL patients (mainly during earlier stages of disease) and may potentially mediate therapeutic responses if their numbers and activation states can be sufficiently increased by tumor vaccines.