RESUMO
A pesar de los avances en los protocolos de tratamiento y en las medidas de soporte en pacientes con Leucemia Mieloide Aguda (LMA), 27% presentan recaídas de la enfermedad. Esto se debe, entre otras causas, a la persistencia de pequeñas cantidades de células malignas (blastos) resistentes a la terapia. Estas pequeñas cantidades de blastos remanentes se denominan Enfermedad Mínima Residual (EMR). La determinación de EMR requiere de técnicas no solo muy sensibles, sino también específicas, y permite evaluar la respuesta individual a la terapia. La introducción de la EMR como parámetro de respuesta y estratificación está bien definida en Leucemia Linfoblástica Aguda (LLA). Por el contrario, aunque existen publicaciones sobre el impacto pronóstico de la EMR en LMA, aún no se encuentra incluida en forma sistemática en los protocolos nacionales actuales, entre otros motivos, por lo laborioso de la determinación y por la necesidad de validación de la misma. Debe tenerse en cuenta que el inmunofenotipo de los blastos mieloides suele ser más heterogéneo que el de los blastos en LLA, presentando, en muchos casos, subpoblaciones diferentes entre sí, lo cual dificulta su detección certera y no hay consenso definido en cuanto a la metodología más eficaz. En este trabajo describimos una nueva estrategia de marcación y análisis estandarizada en un estudio multicéntrico internacional para LMA y la utilidad de la EMR como parámetro de respuesta y de estratificación. Asimismo, detallamos los resultados preliminares de nuestra cohorte de pacientes (AU)
Despite the improvement in treatment and supportive care of patients with Acute Myeloid Leukemia (AML), 27% of them relapse. This is due to the persistence of small amounts of malignant cells (blasts) resistant to therapy, among other causes. These small amounts of blasts are called Minimal Residual Disease (MRD). The determination of MRD requires not only techniques with high sensitivity but also with high specificity, and allows to evaluate the individual response to treatment. The introduction of MRD as a response parameter is well established in Acute Lymphoblastic Leukemia (ALL), and it is used in current stratification protocols. On the other hand, even though there are some reports regarding the prognostic impact of MRD in AML, it is still not included in the current national protocols due to the lack of validation of the determination, among other causes. This is due to the fact that the immunophenotype of myeloid blasts is more heterogeneous than in ALL, presenting different subpopulations, which difficults their accurate detection. Thus, there is still no consensus regarding the most effective approach. In this article, we describe a new staining and analysis strategy standardized by an international multicentric study, and the utility of EMR as a response and stratification parameter. Additionally, we show the preliminary results of our patient cohort. (AU)
Assuntos
Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Imunofenotipagem/instrumentação , Neoplasia Residual/diagnóstico , Citometria de Fluxo/instrumentaçãoRESUMO
Las técnicas de Biología Molecular de última generación, como es la secuenciación masiva en paralelo o NGS (Next Generation Sequencing), permite obtener gran cantidad de información genómica, la cual muchas veces va más allá de la detección de una variante patogénica en un gen que explique la patología (hallazgo primario). Es así como surgió desde hace años la discusión internacional respecto a la decisión a tomar frente a los hallazgos secundarios accionables, es decir, aquellos hallazgos de variantes clasificadas como patogénicas o probablemente patogénicas que no están relacionadas con el fenotipo del paciente, pero que tiene alguna medida preventiva o tratamiento posible y, por lo tanto, podría ser de utilidad para la salud del paciente. Luego de revisar la bibliografía internacional y debatir entre los expertos del Hospital de Pediatría Garrahan, se logró establecer una política institucional y reforzar el hecho de que se trata de una disciplina multidisciplinaria. Así, fue posible definir que solo se atenderá las cuestiones relacionadas con la edad pediátrica, dejando para un tratamiento posterior aquellas variantes detectadas en genes que sean accionables en edad adulta. En el Hospital Garrahan, ha sido posible definir claramente cómo proceder frente a los hallazgos secundarios, al adaptar el consentimiento informado a esta necesidad, definiendo cuándo serán informados, y sabiendo que serán buscados intencionalmente en los genes clínicamente accionables enlistados en la última publicación del American College of Medical Genetics and Genomics, siempre y cuando el paciente/padre/tutor lo consienta (AU)
The latest generation of molecular biology techniques, including massive parallel sequencing or NGS (Next Generation Sequencing), allows us to obtain a whealth of genomic information, which often goes beyond the detection of a pathogenic variant in a gene that explains the pathology (primary finding). As a result, an international discussion has arisen over the years regarding the decision-making concerning actionable secondary findings, it means, those findings of variants classified as pathogenic or probably pathogenic that are not related to the patient's phenotype, but which have some possible preventive measure or treatment and, therefore, could be useful for the patient's health. After reviewing the international literature and discussing among the experts of the Hospital de Pediatría Garrahan, an institutional policy was established and the concept that this is a multidisciplinary discipline was reinforced. Consequently, it has been defined that only issues related to children will be addressed, reserving those variants detected in genes that are actionable in adulthood for later treatment. At Garrahan Hospital, we were able to clearly define how to proceed with secondary findings by adapting the informed consent to this need, defining when they will be reported, and knowing that they will be intentionally searched for in the clinically actionable genes listed in the latest publication of the American College of Medical Genetics and Genomics, as long as the patient/parent/guardian consents (AU)
Assuntos
Humanos , Genoma Humano/genética , Achados Incidentais , Sequenciamento de Nucleotídeos em Larga Escala , Medicina Genômica/tendências , Hospitais Pediátricos , Biologia Molecular/tendências , Consentimento Livre e EsclarecidoRESUMO
Rhabdomyosarcoma (RMS) is the most frequent soft tissue sarcoma (STS) in children and adolescents. In Spain the annual incidence is 4.4 cases per million children < 14 years. It is an uncommon neoplasm in adults, but 40% of RMS are diagnosed in patients over 20 years of age, representing 1% of all STS in this age group. RMS can appear anywhere in the body, with some sites more frequently affected including head and neck, genitourinary system and limbs. Assessment of a patient with suspicion of RMS includes imaging studies (MRI, CT, PET-CT) and biopsy. All patients with RMS should receive chemotherapy, either at diagnosis in advanced or metastatic stages, or after initial resection in early local stages. Local control includes surgery and/or radiotherapy depending on site, stage, histology and response to chemotherapy. This guide provides recommendations for diagnosis, staging and treatment of this neoplasm.
Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Guias de Prática Clínica como Assunto/normas , Rabdomiossarcoma/terapia , Criança , Terapia Combinada , Humanos , Incidência , Rabdomiossarcoma/diagnóstico por imagem , Rabdomiossarcoma/epidemiologia , Rabdomiossarcoma/patologia , Espanha/epidemiologiaRESUMO
BACKGROUND: Neonatal tumors represent an extremely rare and heterogeneous disease with an unknown etiology. Due to its early onset, it has been proposed that genetic factors could play a critical role; however, germline genetic analysis is not usually performed in neonatal cancer patients PATIENTS AND METHODS: To improve the identification of cancer genetic predisposition syndromes, we retrospectively review clinical characteristics in 45 patients with confirmed tumor diagnosis before 28 days of age, and we carried out germline genetic analysis in 20 patients using next-generation sequencing and directed sequencing. RESULTS: The genetic studies did not find any germline mutation except patients diagnosed with bilateral retinoblastoma who harbored RB1 germline mutations. CONCLUSIONS: Our results suggest that genetic factors have almost no higher impact in most neonatal tumors. However, since the heterogeneity of the tumors and the small sample size analyzed, we recommend complementary and centralized germline studies to discard the early onset as an additional criterion to take into account to improve the identification of cancer genetic predisposition syndromes in neonates.
Assuntos
Doenças Fetais/genética , Neoplasias/genética , Feminino , Predisposição Genética para Doença , Testes Genéticos , Mutação em Linhagem Germinativa , Humanos , Recém-Nascido , Masculino , Estudos RetrospectivosRESUMO
We studied the epidemiologic triad-related factors influencing human papilloma virus (HPV) persistence in Mexican women with systemic lupus erythematosus (SLE). Patients aged ≥18 years with SLE (American College of Rheumatology criteria), with and without HPV persistence, were selected. Groups were analyzed by (1) host: clinical disease characteristics; (2) agent: (I) infectious (prevalence, incidence, HPV genotype and co-infections (≥2 HPV genotypes or mycoplasmas)), (II) chemical (contraceptives and immunosuppressive drugs) and (III) physical (vitamin D deficiency) and (3) environment. A total of 121 SLE patients were selected over a two-year period. (1) Host: mean age 45.8 years and disease duration 12.7 years. (2) Agent: (I) infectious. HPV infection prevalence in the second sample was 26.4%, high-risk HPV genotypes 21.5% and co-infections 7.4%. HPV infection incidence was 13.2%, persistence 13.2% and clearance 15.7%. (II) Chemical: use of oral hormonal contraceptives 5% and immunosuppressive treatment 97.5%. (III) Physical: Vitamin D levels were similar in both groups. (3) Environment: (I) natural. A total of 60.6% of patients were residents of Puebla City. (II) Social: The mean education level was 10.9. Poverty levels were: III degree 52.4%, IV degree 28% and II degree 17%. (III) Cultural behavioral: Onset of sexual life was 20.5 years, 10% had ≥3 sexual partners and 51.2% were postmenopausal. In conclusion, no factor of the epidemiologic triad was associated with HPV infection prevalence.
Assuntos
Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Infecções por Papillomavirus/epidemiologia , Adulto , Idoso , Estudos de Coortes , Meio Ambiente , Feminino , Humanos , México/epidemiologia , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Adulto JovemRESUMO
Los tumores sincrónicos del tracto genital femenino son un entidad infrecuente que plantea un reto en el diagnóstico diferencial con la enfermedad metastásica. La mayoría de ellos son cánceres de endometrio y ovario, siendo los tumores sincrónicos de endometrio (CE) y trompa (CT) una asociación excepcional. Presentamos el caso de una paciente de 54 años con un diagnóstico preoperatorio de CE en la en la pieza quirúrgica se desveló la existencia de un tumor sincrónico de trompa izquierda. A propósito de este caso se realiza una revisión del tema haciendo hincapié en cómo llegar a un correcto diagnóstico de los tumores independientes descartando la extensión tumoral y la enfermedad metastásica.
Synchronous primary cancers of gynecological tract are uncommon and a challenge in the differential diagnosis with metastatic disease. Most of them are endometrial and ovarian cancers. Synchronous primary endometrial (EC) and tube fallopian cancers (TC) are a very rare association. We report the case of a patient of 54 years with EC preoperative diagnosis with synchronous left TC postoperative diagnosis. We review the topic emphasizing how to reach a correct diagnosis of tumors independent refusing the tumor invasion and metastatic disease.
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias do Endométrio/patologia , Neoplasias das Tubas Uterinas/patologia , Neoplasias Primárias Múltiplas/cirurgia , Neoplasias do Endométrio/cirurgia , Diagnóstico Diferencial , Neoplasias das Tubas Uterinas/cirurgia , Neoplasias Primárias Múltiplas/patologiaRESUMO
Mycosis fungoides (MF), the most common primary cutaneous T-cell lymphoma, is unusual in children. OBJECTIVES: We aimed to describe the epidemiologic, clinical, histopathologic, and immunophenotypic characteristics of MF as well as treatments and course of disease in a pediatric case series. MATERIAL AND METHOD: Data for all patients admitted to our pediatric hospital (Hospital Dr. J. P. Garrahan) in Argentina with a clinical and histopathologic diagnosis of MF between August 1988 and July 2014 were included. RESULTS: A total of 14 patients were diagnosed with MF. The ratio of boys to girls was 1:1.33. The mean age at diagnosis was 11.23 years (range, 8-15 years). The mean time between onset and diagnosis was 3.5 years (range, 4 months-7 years). All patients had hypopigmented MF and 42% also presented the features of classic MF. Seven (50%) had the CD8+ immunophenotype exclusively. Seventy-eight percent were in stage IB at presentation. Phototherapy was the treatment of choice. Four patients relapsed at least once and skin lesions progressed in 3 patients. All patients improved. CONCLUSIONS: MF is unusual in children. The hypopigmented form is the most common. Diagnosis is delayed because the condition is similar to other hypopigmented diseases seen more often in childhood. Although prognosis is good, the rate of recurrence is high, so long-term follow-up is necessary.
Assuntos
Hospitais Pediátricos , Micose Fungoide/epidemiologia , Neoplasias Cutâneas/epidemiologia , Adolescente , Corticosteroides/uso terapêutico , Idade de Início , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Argentina/epidemiologia , Criança , Estudos Transversais , Diagnóstico Tardio , Erros de Diagnóstico , Feminino , Hospitais Pediátricos/estatística & dados numéricos , Humanos , Hipopigmentação/etiologia , Masculino , Micose Fungoide/tratamento farmacológico , Micose Fungoide/patologia , Micose Fungoide/radioterapia , Terapia PUVA , Recidiva , Estudos Retrospectivos , Dermatopatias/diagnóstico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/radioterapia , Terapia UltravioletaRESUMO
The aim of this work was to study phosphate (P) solubilization (and the processes involved in this event) by Talaromyces flavus (BAFC 3125) as a function of carbon and/or nitrogen sources. P solubilization was evaluated in NBRIP media supplemented with different carbon (glucose, sorbitol, sucrose, and fructose) and nitrogen (L-asparagine, urea, ammonium sulfate (AS), and ammonium nitrate (AN) combinations. The highest P solubilization was related to the highest organic acid production (especially gluconic acid) and pH drop for those treatments where glucose was present. Also P solubilization was higher when an inorganic nitrogen source was supplemented to the media when compared to an organic one. Although not being present an organic P source, phosphatase activity was observed. This shows that P mineralization and P solubilization can occur simultaneously, and that P mineralization is not induced by the enzyme substrate. The combination that showed highest P solubilization was for AN-glucose. The highest acid phosphatase activity was for AS-fructose, while for alkaline phosphatase were for AS-fructose and AN-fructose. Acid phosphatase activity was higher than alkaline. P solubilization and phosphatase activity (acid and alkaline) were influenced by the different carbon-nitrogen combinations. A better understanding of phosphate-solubilizing fungi could bring a better use of soil P.
Assuntos
Fosfatos de Cálcio/metabolismo , Carbono/metabolismo , Nitrogênio/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Talaromyces/enzimologia , Talaromyces/metabolismo , Meios de Cultura/químicaRESUMO
Pasteurella multocida belongs to the normal flora of the respiratory and digestive tract of many animals. Animal exposure is a considerable risk factor for Pasteurella infection. P. multocida is the most common cause of local infection after an animal bite but is an unusual cause of meningitis. We present a case of bacterial meningitis by P. multocida in a 37-year-old man who worked in a pig farm and was bitten by a pig. The patient had a defect located in the lamina cribosa and this lesion could be the gateway of the infection, although in this case the infection could also be acquired through the pig bite. The bacteria was identified as P. multocida with the biochemical test API 20E (bioMérieux). In agreement with findings in the literature, the strain was susceptible in vitro to penicillin, ampicillin, cefotaxime, ceftriaxone ciprofloxacin, levofloxacin, imipenem and tetracycline.
Assuntos
Meningites Bacterianas/diagnóstico , Exposição Ocupacional , Infecções por Pasteurella/diagnóstico , Pasteurella multocida/isolamento & purificação , Criação de Animais Domésticos , Animais , Antibacterianos/farmacologia , Humanos , Masculino , Meningites Bacterianas/microbiologia , Testes de Sensibilidade Microbiana , Infecções por Pasteurella/microbiologia , SuínosRESUMO
Pasteurella multocida belongs to the normal flora of the respiratory and digestive tract of many animals. Animal exposure is a considerable risk factor for Pasteurella infection. P. multocida is the most common cause of local infection after an animal bite but is an unusual cause of meningitis. We present a case of bacterial meningitis by P. multocida in a 37-year-old man who worked in a pig farm and was bitten by a pig. The patient had a defect located in the lamina cribosa and this lesion could be the gateway of the infection, although in this case the infection could also be acquired through the pig bite. The bacteria was identified as P. multocida with the biochemical test API 20E (bioMérieux). In agreement with findings in the literature, the strain was susceptible in vitro to penicillin, ampicillin, cefotaxime, ceftriaxone ciprofloxacin, levofloxacin, imipenem and tetracycline.
Assuntos
Meningites Bacterianas , Pasteurella multocida , SuínosRESUMO
Pasteurella multocida belongs to the normal flora of the respiratory and digestive tract of many animals. Animal exposure is a considerable risk factor for Pasteurella infection. P. multocida is the most common cause of local infection after an animal bite but is an unusual cause of meningitis. We present a case of bacterial meningitis by P. multocida in a 37-year-old man who worked in a pig farm and was bitten by a pig. The patient had a defect located in the lamina cribosa and this lesion could be the gateway of the infection, although in this case the infection could also be acquired through the pig bite. The bacteria was identified as P. multocida with the biochemical test API 20E (bioMérieux). In agreement with findings in the literature, the strain was susceptible in vitro to penicillin, ampicillin, cefotaxime, ceftriaxone ciprofloxacin, levofloxacin, imipenem and tetracycline.(AU)
Assuntos
Meningites Bacterianas , Suínos , Pasteurella multocidaRESUMO
La mayoría de las Leucemias Agudas (LA) pediátricas pueden clasificarse como Linfoblásticas (principalmente de fenotipo B o T) o Mieloblásticas dependiendo del linaje celular de los blastos, recibiendo tratamiento específico de acuerdo a esta caracterización. La inmunotipificación de las LA se basa en la evaluación de la expresión de antígenos de superficie y/o intracitoplasmáticos de diferenciación linfoide (B o T) o mieloide (My) en los blastos, lo cual permite definir la estirpe celular y clasificar la LA de acuerdo al grado de maduración. Sin embargo, existen grupos particulares poco frecuentes de LA cuya clasificación resulta dificultosa y por eso se las denomina LA de linaje ambiguo (fenotipo mixto/indiferenciadas) y LA de linaje dendrítico. Las de fenotipo mixto son aquellas en las que los blastos expresan marcadores de más de un linaje, y las indiferenciadas aquellas que no expresan antígenos específicos para ningún linaje. Diferentes convenciones se han ido desarrollando para definir y clasificar estos fenotipos inusuales, siendo la más actualizada la propuesta por la Organización Mundial de la Salud (2008). De acuerdo a estas pautas, de 1301 casos de LA diagnosticados entre abril de 1994 y abril de 2009, 28 fueron re-clasificados como LA de linaje Ambiguo, 3 como leucemia mieloide aguda minimamente diferenciadas y 3 como LA de células dendríticas. Debido a lo infrecuente de estos casos, su caracterización resulta relevante, ya que la bibliografía presenta, en general, sólo comunicaciones esporádicas de estos fenotipos particulares. Dada la importante casuística del Hospital Garrahan y el amplio seguimiento de los pacientes, el relevamiento de estos casos inusuales permite caracterizarlos desde el inmunofenotipo, la morfología/citoquímica, la citogenética/biología molecular y evaluar su presentación clínica, evolución, respuesta al tratamiento y sobrevida libre de eventos con la finalidad de colaborar con la definición de su pronóstico y eventualmente con la elaboración de protocolos de tratamiento diferenciados para estos subgrupos de LA (AU)
The majority of childhood acute leukemias (AL) can be classified as lymphoblastic (mainly phenotype B or T) or myeloblastic, depending on the cell lineage of the blasts, requiring specific treatment according to this characterization. Immunotypification of AL is based on surface and/or intracytoplasmic antigen expression with lymhoid (B or T) or myeloide (My) blast differentiation, allowing definition of cell lineage and classification of the AL according to the grade of maturation. Nevertheless, there are rare cases of AL that are difficult to classify, denominated AL of ambiguous lineage (mixed/undifferentiated lineage) and acute dendritic cell leukemia. In AL of the mixed phenotype, the blasts express markers of more than one lineage and in undifferentiated AL, the blasts lack antigen expression of any specific lineage. Different conventions have tried to define and classify these unusual phenotypes, among which the most recent proposal of the World Health Organization (2008). According to the criteria of the latter, of 1301 cases of AL diagnosed between April 1994 and April 2009, 28 were re-classified as AL of ambiguous lineage, 3 as minimally differentiated acute myeloid leukemia, and 3 as acute dendritic cell leukemia. Characterization of these cases is important, as in the literature only sporadic reports of these rare phenotypes are found. Given the large number of patients with a long follow-up of the Garrahan Hospital, a review of these unusual cases allowed characterization from the point of view of the immunophenotype, morphology/cytochemistry, cytogenetics/molecular biology and to evaluate clinical presentation, evolution, response to treatment, and event-free survival to help define the prognosis and develop protocols for the treatment of these subgroups of AL (AU)
Assuntos
Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Leucemia Aguda Bifenotípica/classificação , Leucemia Aguda Bifenotípica/diagnóstico , Leucemia Aguda Bifenotípica/genética , Leucemia/classificação , Imunofenotipagem , Células Dendríticas , Doença AgudaRESUMO
Se realizó una investigación descriptiva y transversal, con una muestra de 107 pacientes que sufrieron una Enfermedad Cerebro Vascular (E.C.V.) durante el año 1999 en San Juan y Martínez, Pinar del Río con el objetivo de caracterizar clínica y epidemiológicamente la enfermedad en nuestra área de salud. La enfermedad se presentó con mayor frecuencia en hombres de 50 a 70 años de edad y en la raza negra. Los factores de riesgo más frecuentes fueron el tabaquismo, la Hipertensión Arterial y los ictus previos. Fallecieron 32 pacientes, predominando como causas de muerte el Infarto Agudo del Micardio, La Neumonía y las Arritmias Cardíacas. La monoplejia branquial derecha, le hemiplejia derecha y las afanasias fueron las secuelas neurológicas mas frecuentes que se presentaron después de los ictus ocurridos, donde predominaron los Ataques Transitorios de Isquemia (A.T.I.), los ictus trombóticos y la hemorragia subaracnoidea. Se utilizó el método estadístico chi cuadrado para el procesamiento estadístico de los resultados...(AU)
Assuntos
/etiologiaAssuntos
Ruptura Esplênica/diagnóstico por imagem , Adulto , Animais , El Salvador/etnologia , Emergências , Humanos , Malária Vivax/complicações , Malária Vivax/etnologia , Malária Vivax/patologia , Masculino , Plasmodium vivax/isolamento & purificação , Ruptura Espontânea , Esplenectomia , Ruptura Esplênica/etnologia , Ruptura Esplênica/etiologia , Ruptura Esplênica/cirurgia , UltrassonografiaRESUMO
Un grupo de investigadores de la Universidad de Carabobo y Maravén, llevaron a cabo un experimento involucrando a los 350 pobladores del caserio Las Majadas en el control y prevención de la malaria mediante la educación sanitaria, organización comunal y uso del mosquitero impregnado con Permetrina. En mayo de 1986 con la ayuda de la comunidad, se impregnaron 33 de los 55 mosquiteros existentes. Seis meses más tarde, en octubre, el equipo volvio a la comunidad y entrevistaron a 21 de las 33 personas que habían contraido la malaria en al intervalo enero-octubre, 1986. Se encontro que hubo un brote serio en el mes de junio que solo produjo 22 casos. Catorce de las victimas dormian en sitios sin ninguna protección contra el mosquito..