Subpoblaciones de linfocitos T en adultos mayores cubanos con leucemia linfoide crónica / Subpopulations of T lymphocytes in Cuban older adults with chronic lymphoid leukemia

Introducción: la inmunosenescencia está asociada con un mayor riesgo de desarrollo de cáncer. Dentro de las hemopatías malignas que afectan a este grupo de edad, está la leucemia linfoide crónica (LLC), caracterizada por trastornos en la inmunidad adaptativa que incluye las subpoblaciones de linfocitos T. Objetivo: Determinar la frecuencia de las subpoblaciones de linfocitos T en los pacientes adultos mayores con leucemia linfoide crónica evaluados en el Instituto de Hematología e Inmunología de Cuba. Métodos: Se realizó un estudio transversal en 30 adultos mayores con leucemia linfoide crónica. Se cuantificaron los linfocitos TCD3+CD4+ y TCD3+CD8+ en sangre periférica por citometría de flujo. Para la lectura y el análisis de los datos se empleó un citómetro de flujo Beckman Coulter Gallios. Se utilizaron los valores porcentuales, la media y la desviación estándar. Se consideró estadísticamente significativo si p≤0.05. Resultados: Hubo un predominio de hombres que representaron el 56,7 por ciento y del grupo de 70-79 años de edad. No se reportó ningún adulto mayor con LLC con valores altos ni normales de linfocitos TCD3+CD4+. Predominaron los hombres con valores bajos porcentuales de linfocitos TCD3+CD4+, TCD3+CD8+ e inversión del índice CD4/CD8 en relación con las mujeres. Conclusiones: Los adultos mayores con LLC presentan alteraciones en el número de las subpoblaciones de linfocitos T. La acción de estas células en relación al crecimiento de células B malignas aún es desconocido y resulta importante determinar si esto puede reflejar un intento de evasión de las células tumorales al control inmunológico(AU)

Introduction: Immunosenescence is associated with an increased risk of cancer development. Among the malignant hemopathies that affect this age group, it is chronic lymphoid leukemia (CLL), characterized by disorders in adaptive immunity, which include subpopulations of T lymphocytes. Objective: To determine frequency of T lymphocyte subpopulations in older adult patients with chronic lymphoid leukemia evaluated at the Institute of Hematology and Immunology of Cuba. Methods: A cross-sectional study was conducted in 30 older adults with chronic lymphoid leukemia. TCD3+CD4+ and TCD3+CD8+ lymphocytes were quantified in peripheral blood by flow cytometry. A Beckman Coulter Gallios flow cytometer was used to read and analyze the data. The percentage values, the mean and the standard deviation were used. It was considered statistically significant if p≤0.05. Results: There was a predominance of men who represented 56.7 percent and the age group of 70-79 years. No older adults with CLL with high or normal values of TCD3+CD4+ lymphocytes were reported. Men predominated with low percentage values of TCD3+CD4+, TCD3+CD8+ lymphocytes and inversion of the CD4/CD8 ratio in relation to women. Conclusions: Older adult with CLL present alterations in the number of T lymphocyte subpopulations. The role of these cells in relation to the growth of malignant B cells it is unknown and it turns out important to determine if this may reflect an attempt to evade tumor cells from immune control(AU)

Satisfacción de pacientes y prestadores de servicios en el Instituto de Hematología e Inmunología / Satisfaction of Patients and Service Providers in the Institute of Hematology and Immunology

Introducción: La satisfacción del paciente y el prestador de servicio asistencial de salud es una variable multidimensional de la calidad en la atención médica. La comunicación, la atención y cortesía, el tiempo de espera percibido, la aplicación de una tecnología de avanzada y una infraestructura idónea son los factores que se deben trabajar para incrementar dicha satisfacción. Objetivo: Identificar el nivel de satisfacción de pacientes, familiares y prestadores de servicios en el Instituto de Hematología e Inmunología. Métodos: Se realizó un estudio descriptivo de corte transversal, durante cinco años (2017-2021). El universo lo conformaron 1004 personas, seleccionados mediante un muestreo aleatorio simple. Se aplicaron para la evaluación de la satisfacción las técnicas de encuestas y entrevistas. Resultados: Se identificó el nivel de satisfacción de las personas respecto a las dimensiones evaluadas sobresaliendo en más del 90 por ciento el trato recibido, la eficiencia en los servicios prestados y la privacidad en salas de asistencia médica. Resultó ser de un 93 por ciento el compromiso y la entrega de los prestadores de servicios y más del 70 por ciento del personal se capacitó. Se analizaron varios indicadores a partir de encuestas de tipo cerradas, abiertas y entrevistas. Conclusiones: La identificación del nivel de satisfacción de pacientes, familiares y prestadores de servicios permite mitigar o eliminar la mayoría de las inconformidades lo que contribuye a la mejora en los servicios asistenciales, docentes e investigativos, que avalan los logros alcanzados por el instituto en la actualidad(AU)

Introduction: Patient and healthcare provider satisfaction is a multidimensional variable of healthcare quality. Communication, care and politeness, the perceived waiting time, the application of advanced technology, as well as an adequate infrastructure, are the factors that should be worked on to increase such satisfaction. Objective: To identify the level of satisfaction of patients, family members and service providers at the Institute of Hematology and Immunology. Methods: A descriptive and cross-sectional study was carried out during five years (2017-2021). The universe consisted of 1004 people, selected by simple random sampling. The survey and interview techniques were used to evaluate satisfaction. Results: The level of satisfaction of the people was identified, with respect to the evaluated dimensions; received treatment, efficiency of provided services and privacy in medical care rooms stood out in more than 90 percent. The commitment and dedication of the service providers was 93 percent, while more than 70 percent of the personnel received training. Several indicators were analyzed based on closed or open-ended surveys and interviews. Conclusions: The identification of the level of satisfaction among patients, family members and service providers allows mitigating or eliminating most of the nonconformities, contributing to the improvement in care, teaching and research services, which confirms the achievements attained by the institute nowadays(AU)

Biomarkers of sequela in adult patients convalescing from COVID-19.

Different biomarkers for SARS-CoV-2 have been linked to detection, diagnosis, treatment, disease progression, and development of new drugs and vaccines. The objective of this research was to evaluate various hematological, biochemicals, immunological, radiological and spirometric parameters in 20 adult patients convalescing from COVID-19 and their possible relationship with the clinical course of the disease. The frequencies of categorical variables were compared using the chi-square and Fisher's exact test. The levels of statistical significance were denoted in each figure legend. Two-dimensional clustering analysis was performed using MeV software from TIGR. The tests with P value of ≤ 0.05 were considered statistically significant. Most of the patients studied presented alterations in dissimilar laboratory, radiological and spirometric parameters, which were related to the clinical evolution of the disease. The results obtained show that certain hematological, biochemical, immunological and radiological parameters can be considered as biomarkers of sequela in adult COVID-19 patients, which allows their stratification, according to the degree of involvement or sequela, into three groups: I (mild degree of involvement or sequela), without lung lesions on computerized axial tomography (CT scan) and high values of IgG, C3 and hemoglobin, II (moderate degree of involvement or sequel), without lung lesions on CT scan, characterized by high levels of CD3+/CD4+ T lymphocytes and the rest of the variables with low values and III (severe degree of involvement or sequela), with lung lesions on CT scan and high values of erythrocyte sedimentation rate, monocytes and neutrophils, associated with lymphopenia and decreased concentrations of IgG and C3.

Implementación del sistema de gestión de calidad en el Instituto de Hematología e Inmunología / Implementation of the Quality Management System in the Institute of Hematology and Immunology

Introducción: Un sistema de gestión de calidad brinda la estructura organizativa, los procesos, los procedimientos y las herramientas para implementar las actividades y alcanzar los objetivos requeridos. Es un proceso en el que participan directivos, operativos y administrativos. Todos deben reconocer y asumir su responsabilidad para el éxito de la implementación o mejoramiento del sistema y deben esforzarse para alcanzarlo. Objetivo: Exponer el proceso de implementación del sistema de gestión de calidad del Instituto de Hematología e Inmunología. Métodos: Se realizó una investigación descriptiva. Se realizaron encuestas, entrevistas y auditorías para mostrar el desarrollo del sistema de gestión de calidad del Instituto de Hematología e Inmunología. El período de estudió fue de 2017-2020 e incluyó 32 áreas del instituto. Resultados: Se crearon los documentos del sistema de gestión de calidad y el plan de gestión. Se capacitó al personal. Se definieron las políticas, el objetivo y la proyección estratégica de la calidad. Se elaboró y se puso en ejecución todo el sistema documental, con un total de más de 590 documentos. Las tareas derivadas del plan de gestión de la calidad se cumplieron en un 81,25 por ciento, esto permitió identificar las áreas de mejoras Conclusiones: La implementación del sistema de gestión de calidad es trascendental para elevar el buen desempeño de una organización de salud y constituye el motor impulsor para lograr la calidad merecida en todos los servicios asistenciales que brinda, lo cual demuestra su importancia para alcanzar los resultados que espera y necesita el sistema de salud cubano(AU)

Introduction: A quality management system provides the organizational structure, processes, procedures and tools to implement activities and achieve the required objectives. It is a process with the participation of management, operational and administrative personnel. All of them must recognize and assume their responsibility for the successful implementation or improvement of the system and must strive to achieve it. Objective: To describe the implementation process of the quality management system in the Institute of Hematology and Immunology. Methods: A descriptive research was carried out. Surveys, interviews and audits were conducted to show the development of the quality management system in Institute of Hematology and Immunology. The study period was 2017-2020 and included 32 institutional areas. Results: The corresponding documents were created for the quality management system and the management plan. The personnel received training. Quality policies, objective and strategic projection were defined. The entire document system was developed and implemented, with a total of more than 590 documents. The tasks derived from the quality management plan were completed at 81.25 percent, which allowed the identification of areas for improvement. Conclusions: The implementation of the quality management system is transcendental to raise the good performance of a health organization, as well as the driving force to achieve the deserved quality in all the care services provided by any institution, which shows its importance to achieve the outcomes expected and needed by the Cuban health system(AU)

Safety and immunogenicity of the FINLAY-FR-1A vaccine in COVID-19 convalescent participants: an open-label phase 2a and double-blind, randomised, placebo-controlled, phase 2b, seamless, clinical trial.

BACKGROUND: A phase 1, clinical trial to evaluate FINLAY-FR-1A vaccine in COVID-19 convalescent individuals was completed. Here, we report results of the phase 2, clinical trial. METHODS: We studied 450 convalescent participants with a history of asymptomatic, mild, or moderate COVID-19 at the National Institute of Hematology and Immunology and the National Centre for Sexual Education in Havana, Cuba. The study included adults aged 19-78 years who had recovered from COVID-19 and had had a negative PCR test at least 2 months before the initiation of the study. Phase 2 was done sequentially in two stages. The first stage to assess safety comprised an open, non-controlled phase 2a study in participants aged 60-78 years who received a single dose of the FINLAY-FR-1A vaccine (50 µg of recombinant dimeric receptor binding domain [RBD]). The second stage comprised the placebo-controlled, double-blind, phase 2b trial in participants aged 19-78 years, where participants were randomly assigned (4:1) into two groups: an experimental group vaccinated with a single dose of the FINLAY-FR-1A vaccine, and a control (placebo) group injected with vaccine excipient. The primary outcomes were safety, evaluated 28 days after vaccination by the occurrence of serious adverse events in all participants, and successful immune response, assessed by neutralising antibody ELISA, and defined as half-maximal surrogate virus neutralisation titres of 250 or more. Secondary endpoints included vaccine immunogenicity assessed by ELISA anti-RBD and live-virus neutralisation test. All randomly assigned participants were included in the safety analysis (safety population), and immunogenicity was evaluated in participants without study interruptions (per-protocol population). The trial is registered with the Cuban Public Registry of Clinical Trials, RPCEC00000366-En and WHO-ICTRP and is complete. FINDINGS: From April 9, 2021, to April 17, 2021, 663 COVID-19 convalescent participants were enrolled in the study; 213 participants did not meet the selection criteria and 450 volunteers were recruited. 20 participants aged 60-78 years were included in the open, single-group, phase 2a study and 430 participants were randomly assigned to the experimental (n=344) or control groups (n=86) in the phase 2b study of participants aged 19-78 years. 19 (95%) of 20 phase 2a volunteers achieved a successful immune response after vaccination. No vaccine-associated serious adverse events were reported in the whole study population. Minor adverse events were found, the most common being pain at the injection site (105 [29%] of 364 in the intervention group; 13 [15%] of 86 in the placebo group). A successful immune response was found in 289 (81%) of 358 participants 28 days after vaccination. The vaccine elicited a greater than 31-times increase in anti-RBD-IgG antibodies compared with prevaccination rates, and the seroconversion rate was 302 (84%) of 358 on day 28 after vaccination; the geometric mean titres of live-virus neutralisation test increased from 15·4 (95% CI 10·3-23·2) to 400·3 (272·4-588·1) and high response was found against alpha, beta, and delta variants of concern. INTERPRETATION: A single dose of the FINLAY-FR-1A vaccine against SARS-CoV-2 strengthened the pre-existing natural immunity, with excellent safety profile. FUNDING: Cuba's Ministry of Science, Technology, and Environment.

Molecular study of a large cohort of 109 haemophilia patients from Cuba using a gene panel with next generation sequencing-based technology.

INTRODUCTION: In several countries, molecular diagnosis of haemophilia A (HA) and B (HB) is hampered by a lack of resources for DNA analysis. The advent of next-generation sequencing (NGS) has enabled gene analysis at a reasonable cost. AIM: Describe a collaboration between Cuban and Spanish researchers to identify candidate variants and investigate the molecular epidemiology of 106 Cuban haemophilia patients using NGS. PATIENTS/METHODS: The molecular analysis protocol included well-established LR-PCR procedures to detect F8 inversions, NGS with a 30-gene panel to sequence F8 and F9, and multiplex ligation-dependent probe amplification to identify large structural variants. RESULTS: One-hundred and thirty-one candidate variants were identified along F8, F9, and VWF; 72 were unique and 28 (39%) had not been previously recorded. Putative variants were identified in 105/106 patients. Molecular characterization enabled confirmation and reclassification of: 90 HA (85%), 15 HB (14%), and one type 2N VWD (1%). Null variants leading to non-production of FVIII or FIX were common in severe HA (64%), moderate HA (74%), and severe HB (60%), whereas missense variants were frequent in mild HA (57%) and moderate or mild HB (83%). Additional variants in VWF were identified in 16 patients. CONCLUSION: This is the first description of the molecular epidemiology of HA and HB in Cuba. Variants identified in index cases will be of value for local implementation of familial studies and prenatal diagnosis using the molecular approaches available in Cuba. The results of this protocolled genetic study improved the accuracy of the clinical diagnosis and will facilitate management of these patients.

Caracterización del hemograma completo en adultos mayores cubanos tratados con Biomodulina T® / Character i zation of the complete blood count of Cuban older adults treated with Biomodulin a T ®

Introducción: Durante las últimas décadas es evidente el aumento progresivo de los adultos mayores en Cuba. El proceso de envejecimiento provoca cambios en el sistema inmune que afectan su funcionamiento y desarrollo. Objetivo: Caracterizar parámetros hematológicos e inmunológicos mediante el hemograma completo en adultos mayores cubanos antes y después de la administración de la Biomodulina T®. Métodos: Se realizó un estudio descriptivo y observacional para evaluar el efecto de la Biomodulina T® sobre los parámetros del hemograma completo. Se utilizó el paquete estadístico GraphPad Prism (versión 6.00). Los datos que presentaban una distribución normal, se procesaron utilizando la t Student. La prueba de rangos con signo de Wilcoxon se empleó cuando los datos no cumplían una distribución normal, ambos para un nivel de significación de p < 0,05. Resultados: Predominaron las mujeres en relación a los hombres, que representó 27,6 por cientoHubo superioridad de adultos mayores de 76-80 años de edad. El conteo global de leucocitos se mantuvo dentro de parámetros normales y solo en 5 pacientes disminuyeron las plaquetas después de la administración de Biomodulina T. Estos resultados no fueron estadísticamente significativos. Conclusiones: Se demostró que el tratamiento con Biomodulina T® no modifica los diferentes parámetros del hemograma completo en el adulto mayor(AU)

Introduction: In the last decade it has been evident the rise in the older adults in Cuba. The process of aging causes changes in the immune system that affects the development and function. Objective: To characterize hematological and immunological parameters by means of the complete blood count in Cuban older adults before and after the administration of Biomodulin T® Materials and methods: A descriptive and observational study was to conducted to evaluate the use of Biomodulina T, the statistic package used was the GraphPad Prism (version 6.00). The data that showed a normal distribution were processed using the Student´s t test. The Wilcoxon´s signed range test with was used when the data did not comply with the normal distribution. Both for a signification level of p < 0.05. Results: Women predominated in relation to men, representing 27.6 percent. There was a predominance of older adults aged 76-80 years. The global leukocyte count remained within normal parameters and platelets decreased only in 5 patients after the administration of Biomodulina T, that results were not statistically significant. Conclusion: It was shown that the Biomodulina T did not modify the hemogram results in the elderly patients(AU)

Estudio inmunológico en paciente con síndrome de Behcet: reporte de un caso / immunological study in a patient with Behcet Syndrome: a case report

Introducción: El síndrome de Behcet, o enfermedad de Behcet, es un proceso autoinflamatorio crónico, poco frecuente, de etiología desconocida. Es una vasculitis que afecta arterias y venas de todos los calibres, con alteración de la función endotelial, que se expresa clínicamente con lesiones orgánicas variadas. En su fisiopatogenia intervienen factores genéticos, microbianos e inmunológicos. Los síntomas más comunes son las úlceras orales y genitales, inflamaciones oculares (uveítis, retinitis e iritis), lesiones de piel y artritis. Objetivo: Evaluar diversos marcadores de la respuesta inmune en paciente con síndrome de Behcet. Presentación del caso: Paciente masculino. 39 años de edad, con diagnóstico clínico de enfermedad de Behcet con reactantes de fase aguda y marcadores serológicos de autoinmunidad negativa. Las subpoblaciones linfocitarias están dentro de los valores referenciales, sin evidencias de activación linfocitaria. La presencia de una doble población de linfocitos B y los antecedentes familiares, sugieren la existencia de una población de linfocitos B de autoreconocimiento y la posible presencia de factores genéticos, respectivamente. El paciente respondió favorablemente a la terapia con esteroides. Conclusiones: El estudio apoya el criterio de que, en condiciones basales, no se detectan marcadores humorales de autoinmunidad, alteraciones de los valores de las subpoblaciones linfocitarias, ni evidencias de activación linfocitaria, pero no se puede excluir la presencia de una población de linfocitos B de autoreconocimiento(AU)

Introduction: Behcet's syndrome, also known as Behcet's disease is a chronic autoinflammatory process of low frequency and unknown etiology. It's an all sizes arteries and veins affecting vasculitis that causes an alteration of endothelial function and is expressed clinically by organ damage at various levels. Its pathogenesis involves genetic, microbial and immunological factors. The most common symptoms are oral and genital ulcers, eye inflammation (uveitis, iritis and retinitis), skin lesions and arthritis. Objective: to evaluate several inmunological markers in a patient with Behcet syndrome. Case presentation: 39 years old masculine patientwith clinical diagnosis of Behcet disease with negative acute phase reactants and serological authoinmunity markers and lymphocyte populations within referential range, without evidences of lymphocyte activation. The presence of a double B lymphocyte population and familial background, suggest the presence of a self recognitionB lymphocyte population and the probable presence of genetic factors, respectively. There was a good response to steroids treatment. Conclusions: The study supports the idea that at baseline, not humoral autoimmunity markers, changes in the values of lymphocyte subpopulations, and evidence of lymphocyte activation is detected, but can not exclude the presence of a population of B lymphocytes self-recognition(AU)

A single dose of SARS-CoV-2 FINLAY-FR-1A vaccine enhances neutralization response in COVID-19 convalescents, with a very good safety profile: An open-label phase 1 clinical trial.

BACKGROUND: As a first step towards a vaccine protecting COVID-19 convalescents from reinfection, we evaluated FINLAY-FR-1A vaccine in a clinical trial. METHODS: Thirty COVID-19 convalescents aged 22-57 years were studied: convalescents of mild COVID-19, asymptomatic convalescents, both with PCR-positive at the moment of diagnosis; and individuals with subclinical infection detected by viral-specific IgG. They received a single intramuscular injection of the FINLAY-FR-1A vaccine (50 µg of the recombinant dimeric receptor binding domain). The primary outcomes were safety and reactogenicity, assessed over 28 days after vaccination. The secondary outcome was vaccine immunogenicity. Humoral response at baseline and following vaccination was evaluated by ELISA and live-virus neutralization test. The effector T cellular response was also assessed. Cuban Public Registry of Clinical Trials, WHO-ICTRP: https://rpcec.sld.cu/en/trials/RPCEC00000349-En. FINDINGS: No serious adverse events were reported. Minor adverse events were found, the most common, local pain: 3 (10%) and redness: 2 (6·7%). The vaccine elicited a >21 fold increase in IgG anti-RBD antibodies 28 days after vaccination. The median of inhibitory antibody titres (94·0%) was three times greater than that of the COVID-19 convalescent panel. Virus neutralization titres higher than 1:160 were found in 24 (80%) participants. There was also an increase in RBD-specific T cells producing IFN-γ and TNF-α. INTERPRETATION: A single dose of the FINLAY-FR-1A vaccine against SARS-CoV-2 was an efficient booster of pre-existing natural immunity, with excellent safety profile. FUNDING: Partial funding for this study was received from the Project-2020-20, Fondo de Ciencia e Innovación (FONCI), Ministry of Science, Technology and the Environment, Cuba.   RESUMEN. ANTECEDENTES: Como un primer paso hacia una vacuna que proteja a los convalecientes de COVID-19 de la reinfección, evaluamos la vacuna FINLAY-FR-1A en un ensayo clínico. MÉTODOS: Se estudiaron treinta convalecientes de COVID-19 de 22 a 57 años: convalecientes de COVID-19 leve y convalecientes asintomáticos, ambos con prueba PCR positiva al momento del diagnóstico; e individuos con infección subclínica detectada por IgG específica viral. Los participantes recibieron una dosis única por vía intramuscular de la vacuna FINLAY-FR-1A (50 µg del dominio de unión al receptor recombinante dimérico del SARS CoV-2). Las variables de medida primarias fueron la seguridad y la reactogenicidad, evaluadas durante 28 días después de la vacunación. La variable secundaria, la inmunogenicidad. La respuesta humoral, al inicio del estudio y después de la vacunación, se evaluó por ELISA y mediante la prueba de neutralización del virus vivo. También se evaluó la respuesta de células T efectoras. Registro Público Cubano de Ensayos Clínicos, WHO-ICTRP: https://rpcec.sld.cu/en/trials/RPCEC00000349-En. RESULTADOS: No se reportaron eventos adversos graves. Se encontraron eventos adversos leves, los más comunes, dolor local: 3 (10%) y enrojecimiento: 2 (6·7%). La vacuna estimuló un incremento >21 veces de los anticuerpos IgG anti-RBD 28 días después de la vacunación. La mediana de los títulos de anticuerpos inhibidores (94·0%) fue aproximadamente tres veces mayor que la del panel de convalecientes de COVID-19. Se encontraron títulos de neutralización viral superiores a 1:160 en 24 (80%) de los participantes. También hubo un aumento en las células T específicas de RBD que producen IFN-γ y TNF-α. INTERPRETACIÓN: Una sola dosis de la vacuna FINLAY-FR-1A contra el SARS-CoV-2 reforzó eficazmente la inmunidad natural preexistente, con un excelente perfil de seguridad. FINANCIAMIENTO: Se recibió un financiamiento parcial del Proyecto-2020-20, Fondo de Ciencia e Innovación (FONCI), Ministerio de Ciencia, Tecnología y Medio Ambiente, Cuba.

Asociación entre hipoplasia del timo y disminución de inmunoglobulina A / Association between thymus hypoplasia and immunoglobulin A reduction

El sistema inmune madura gradualmente durante la infancia y el nacimiento es un momento crucial para este proceso. El paso por el canal del parto es el primer estímulo que el sistema inmunitario percibe para comenzar así su maduración progresiva. El timo como órgano linfoide primario, es el primero en aparecer entre todos los órganos linfoides; en este órgano ocurre la ontogenia, diferenciación y maduración de los linfocitos T que migran a los órganos linfoides secundarios como linfocitos T inmunocompetentes. La producción de IgA por los linfocitos B es uno de los mecanismos esenciales de respuesta inmune de las mucosas a las que protege en su forma de IgA secretoria. En el Instituto de Hematología e Inmunología, se atendieron en consulta 62 pacientes pediátricos entre uno y cinco años de edad, con antecedentes de infecciones respiratorias agudas frecuentes, con dos o más episodios en un mes, a los que se les diagnosticó por ultrasonografía una disminución del área tímica (hipoplasia). De ellos, 50 por ciento presentó además disminución de la concentración de IgA en suero. Estos resultados sugieren múltiples interrogantes. Consecuentemente, este trabajo tiene como objetivo presentar la asociación hallada entre la disminución del tamaño del timo y la disminución de la concentración en suero de IgA, en un grupo de niños de uno a cinco años, con antecedentes de infecciones respiratorias frecuentes, consultados en el Instituto de Hematología e Inmunología durante un año(AU)

The immune system gradually matures during childhood, and birth is a crucial moment in this process. Transit through the birth canal is the first stimulus perceived by the immune system to start its progressive maturation. The thymus, a primary lymphoid organ as it is, is the first lymphoid organ to appear. It is the site of the ontogeny, differentiation and maturation of the T-lymphocytes migrating to secondary lymphoid organs as immunocompetent T-lymphocytes. IgA production by B-lymphocytes is one of the essential immune response actions performed by mucosas, which they protect in the form of secretory IgA. A study was conducted of 62 pediatric patients aged 1-5 years attending consultation at the Institute of Hematology and Immunology who had a history of frequent acute respiratory infection, with two or more episodes in one month. These patients were ultrasonographically diagnosed with thymus size reduction (hypoplasia). Among them, 50 percent also presented a decrease in serum IgA concentration. These results pose many questions concerning the association between thymus hypoplasia and IgA reduction. The purpose of the study was therefore to present the association found between thymus size reduction and serum IgA concentration decrease in a group of children aged 1-5 years with a history of frequent respiratory infection attending the Institute of Hematology and Immunology during one year(AU)

Avances en el diagnóstico de la enfermedad granulomatosa crónica: primer estudio familiar en Cuba / Advances in the diagnosis of chronic granulomatous disease: the first family study in Cuba

Introducción: La enfermedad granulomatosa crónica es una inmunodeficiencia primaria causada por mutaciones en la enzima NADPH oxidasa. Esta compromete la producción de especies reactivas del oxígeno, que son importantes contra patógenos. La prueba de la oxidación de la dihidrorodamina es un método eficaz para diagnosticar la enfermedad. Objetivo: Demostrar la utilidad de la prueba de la oxidación de la dihidrorodamina y del patrón de herencia en la confirmación del diagnóstico de la enfermedad granulomatosa crónica de un paciente. Métodos: Estudio de caso de una familia con diagnóstico de enfermedad granulomatosa crónica. Se tomó muestra de sangre periférica para citometría de flujo a tres individuos. Se realizó la prueba de la oxidación de la dihidrorodamina bajo estímulo con acetato de forbolmiristato y se evaluaron las subpoblaciones linfocitarias. Las muestras se leyeron en un citómetro GALLIOS, Beckman Coulter. Los datos obtenidos se analizaron en el programa informático Kaluza. Resultados: El paciente masculino tuvo un valor de oxidación de la dihidrorodamina positiva de 0,87 por ciento, que confirmó un patrón de herencia ligado al cromosoma X; mientras que la madre y hermana gemela portadoras tuvieron valores de 46,76 por ciento y 37,32 por ciento, respectivamente. Se encontraron alteraciones en las subpoblaciones linfocitarias. Conclusiones: La prueba de la oxidación de la dihidrorodamina es un método muy efectivo, rápido y sencillo que confirma el diagnóstico de la enfermedad granulomatosa crónica y determina el patrón de herencia y fenotipo de la enfermedad. Además, permite identificar a las mujeres portadoras según la distribución de los neutrófilos normales y los que tienen el gen CYBB mutado(AU)

Introduction: Chronic granulomatous disease is a primary immunodeficiency caused by mutations in the NADPH oxidase enzymes. This compromises the production of oxygen reactive species, which are important against pathogens. The dihydrorhodamine oxidation test is an effective method for diagnosing the disease. Objective: To demonstrate the usefulness of the dihydrorhodamine oxidation test and the inheritance pattern in confirming the diagnosis of chronic granulomatous disease in a patient. Methods: A case study of a family with a diagnosis of chronic granulomatous disease. A peripheral blood sample was taken from three individuals and by flow cytometry. The dihydrorhodamine oxidation test was performed under stimulation with phorbolmyristate acetate, and lymphocyte subpopulations were evaluated. The samples were read on a GALLIOS, Beckman Coulter cytometer. The data obtained were analyzed using the computer program Kaluza. Results: The male patient had a positive dihydrorhodamine oxidation value of 0.87 percent, which confirmed an inheritance pattern linked to the X chromosome; while the carrier mother and twin sister had values 8203;8203;of 46.76 percent and 37.32 percent, respectively. Alterations were found in the lymphocyte subpopulations. Conclusions: The dihydrorhodamine oxidation test is a very effective, fast and simple method that confirms the diagnosis of chronic granulomatous disease and determines the inheritance pattern and phenotype of the disease. In addition, it allows the identification of female carriers according to the distribution of normal neutrophils and those with the CYBB mutation(AU)

CD45 y leucemia linfoide aguda pediátrica / CD45 and childhood acute lymphoblastic leukemia

Introducción: El CD45 se expresa en las células hematopoyéticas, su determinación es indispensable para la clasificación inmunofenotípica de la leucemia linfoide aguda (LLA). Objetivo: Evaluar la expresión del antígeno CD45 en los blastos de pacientes pediátricos con LLA y su relación con las características biológicas, morfológicas y clínicas al inicio de la enfermedad, la respuesta al tratamiento y la supervivencia global (SG) de los enfermos. Métodos: Se estudiaron 160 pacientes con LLA entre diciembre del 2012 y diciembre del 2017, tratados con el protocolo ALL-IC BFM-SG 2009. El inmunofenotipaje celular de la médula ósea se realizó por citometría de flujo. Resultados: El fenotipo B CD45+ predominó en los menores de seis años de edad y en los mayores de diez, el fenotipo T CD45+. Se encontró diferencia significativa entre la ausencia de adenopatías mediastínicas, el fenotipo leucémico y la ausencia de CD45 (p=0.004); entre la respuesta a la prednisona en sangre periférica al día ocho, el fenotipo leucémico y la ausencia de CD45 (p=0.001). Se encontraron diferencias significativas entre la respuesta a la prednisona en sangre periférica el día ocho y la respuesta en médula ósea el día 33, según fenotipo leucémico (p=0.009) y la presencia en los blastos del antígeno CD45 (p=0.02). Se encontró diferencia significativa entre la SG de los enfermos, según fenotipo leucémico y la ausencia del antígeno CD45 (p=0.017). Conclusión: La expresión o ausencia del antígeno de CD45 en los blastos tiene relación con la respuesta al tratamiento y la SG de pacientes pediátricos con LLA(AU)

Introduction: CD45 is expressed in hematopoietic cells, its determination is essential for the immunophenotypic classification of acute lymphoid leukemia (ALL). Objective: To evaluate the expression of the CD45 antigen in the blasts of pediatric patients with ALL and its relationship with the biological, morphological and clinical characteristics at the onset of the disease, the response to treatment and the overall survival (OS) of the patients. Methods: 160 patients with ALL were studied between December 2012 and December 2017, treated with the ALL-IC BFM-SG 2009 protocol. Bone marrow cellular immunophenotyping was performed by flow cytometry. Results: Patients with the CD45 + B phenotype predominated in those under six years of age, while those with a CD45 + T phenotype in those older than ten. A significant difference was found between the absence of mediastinal lymph nodes, the leukemic phenotype and the absence of CD45 (p = 0.004). A significant difference was found between the response to prednisone in peripheral blood at day eight, the leukemic phenotype and the absence of CD45, p = 0.001. Significant differences were found between the response to prednisone in peripheral blood on day eight and the response in bone marrow on day 33, according to leukemic phenotype and the presence in blasts of the CD45 antigen (p = 0.009 and p = 0.02, respectively). A significant difference was found between the OS of patients, according to leukemic phenotype and the absence of the CD45 antigen, p = 0.017. Conclusion: The expression or absence of the CD45 antigen in blasts is related to the response to treatment and OS of pediatric patients with ALL(AU)

Evaluación preliminar de estándares de calidad en el Instituto de Hematología e Inmunología / Preliminary evaluation of quality standards in the Institute of Hematology and Immunology

Introducción: El Instituto de Hematología e Inmunología (IHI), desde el año 2002 comenzó a capacitar a todo el personal en Sistema de Gestión de la Calidad y paulatinamente avanzó en la documentación requerida hasta lograr una política y un Programa de Garantía de la Calidad, basado en normativas nacionales, cumpliendo con el anexo Programa de Perfeccionamiento continuo de la calidad de los servicios hospitalarios. Objetivo: Realizar una evaluación preliminar de estándares de calidad en el IHI, aplicando la última versión del Manual de Acreditación, para solicitar la acreditación hospitalaria. Métodos: Se realizó una evaluación parcial mediante auditorías internas al 90 por ciento de las áreas y se desarrollaron actividades para cumplir con lo solicitado por la Junta Nacional de Acreditación en Salud. Se emplearon diversos métodos, como aplicación de listas de verificación, cursos de capacitación y superación, observación in situ de evidencias objetivas, entrevistas, encuestas y revisión de documentos. Resultados: De los 18 servicios auditados se obtuvo del Estándar Centrado en la Atención y Seguridad a Paciente el cumplimiento del 77 por ciento de los elementos a evaluar; dl Estándar Docencia e Investigación, se cumplió el 88 por ciento y del Estándar Gestión y Seguridad Hospitalaria se cumplió el 87 por ciento de los elementos auditados. Conclusiones: La aplicación preliminar de los estándares de calidad en el IHI ha generado más de 60 documentos, lo cual indica el desarrollo progresivo en esta actividad, además de capacitar al personal en temas de calidad y conocer el estado de satisfacción de pacientes y prestadores de servicios(AU)

Introduction: The Institute of Hematology and Immunology (IHI) had begun training all its personnel in the Quality Management System since 2002 and it gradually progressed in the required documentation until achieving a policy and a Quality Assurance Program, based on national regulations, complying with the annex Program of continuous improvement of the quality of hospital services. Objective: To carry out a preliminary evaluation of quality standards in the IHI, applying the latest version of the Accreditation Manual, in order to request hospital accreditation. Methods: A partial evaluation was carried out through internal audits to 90 percent of the areas and activities were developed to comply with the requirements of the National Health Accreditation Board. Various methods were used, such as: application of checklists, training and improvement courses, on-site observation of objective evidence, interviews, surveys and document review. Results: Of the 18 audited services, compliance with 77 percent of the elements to be evaluated was obtained from the Standard centered on Patient Care and Safety; 88 percent of the Standard related to Teaching and Research was fullfilled and the Hospital Management and Safety Standard achieved 87 percent of the audited elements. Conclusion: The preliminary application of the quality standards in the IHI has generated more than 60 documents. It indicates the progressive development of this activity and at the same time allows for the training of the staff on quality issues and gives us the possibility of knowing the satisfaction status of patients and service providers(AU)

Aspectos más relevantes del síndrome periódico asociado al receptor del factor de necrosis tumoral / Most relevant aspects of tumor necrosis factor receptor associated periodic syndrome

Los desórdenes autoinflamatorios hereditarios constituyen una gama de condiciones heterogéneas que tienen como característica común la aparición de ataques no provocados de inflamación, la cual podría ser sistémica u ocurrir en nichos localizados del organismo. Dentro de estos se encuentran los síndromes hereditarios de fiebre periódica, caracterizados por ataques cortos y recurrentes de fiebre e inflamación localizada grave, que ocurre periódica o irregularmente y que no se explican por las infecciones usuales de la infancia. Forma parte de estas entidades el síndrome periódico asociado al receptor del factor necrosis tumoral, el cual se caracteriza por episodios de fiebre prolongada, mialgias, dolor abdominal, eritema cutáneo migratorio, conjuntivitis o edema periorbitario, con un patrón de herencia autosómico dominante. Lo más importante para el diagnóstico es el análisis genético y su pronóstico está determinado por la aparición de amiloidosis. En 1999, se descubrió su base genética, al identificarse las mutaciones causantes de la enfermedad en el gen que codifica para la superfamilia 1 A del receptor del factor de necrosis tumoral. En años recientes se han logrado avances significativos en el diagnóstico y tratamiento de esta enfermedad gracias a un mejor conocimiento de su patogénesis. En este trabajo se describen los aspectos más relevantes en cuanto a patogénesis, relación de las mutaciones con el fenotipo de la enfermedad, características clínicas y tratamiento(AU)

Hereditary autoinflammatory disorders are a range of heterogeneous conditions that have as a common feature the appearance of unprovoked inflammatory attacks, which may be systemic or occur in localized niches of the body. Among these are hereditary periodic fever syndrome, characterized by short and recurrent attacks of fever and severe localized inflammation, occurring periodically or irregularly and not explained by the usual infections of childhood. Tumor necrosis factor receptor-associated periodic syndrome is part of these entities and is characterized by episodes of prolonged fever, myalgias, abdominal pain, migratory cutaneous erythema, conjunctivitis and/or periorbital edema, with an autosomal dominant inheritance pattern. The most important for the diagnosis is the genetic analysis and its prognosis is determined by the appearance of amyloidosis. In 1999 its genetic basis was discovered by identifying disease-causing mutations in the gene encoding tumor necrosis factor receptor superfamily member 1A. In recent years, significant advances have been achieved in the diagnosis and treatment of this disease, thanks to a better understanding of its pathogenesis. This paper describes the most relevant aspects regarding pathogenesis, relation of mutations with the disease phenotype, clinical characteristics and treatment(AU)

Systemic Ozone Therapy by Rectal Insufflation for Immunoglobulin A Deficiency.

INTRODUCTION: IgA deficiency is a primary immunodeficiency predominantly due to an antibody defect, for which there is no replacement therapy. Treatment consists of prevention and treatment of infections and other associated conditions. Given the immunomodulatory and regulatory properties of the redox balance of ozone therapy in infectious and inflammatory conditions, evaluation of its effect on IgA deficiency is of interest. OBJECTIVE: Assess the benefits and possible adverse effects of ozone treatment in patients with IgA deficiency. METHODS: A monocentric randomized controlled phase 2 clinical trial (RPCEC 00000236) was carried out, after approval by the Institutional Ethics Committee of the Roberto Rodríguez Fernández Provincial General Teaching Hospital in Morón, Ciego de Ávila Province, Cuba. Included were 40 patients aged 5-50 years, distributed in 2 groups of 20, after agreeing to participate and signing informed consent. The experimental group received 2 cycles of ozone by rectal insufflation for 20 days (5 times a week for 4 weeks each cycle) with a 3-month interval between cycles, for a total of 40 doses, with age-adjusted dose ranges. The control group was treated with leukocyte transfer factor (Hebertrans), 1 U per m2 of body surface area subcutaneously, once weekly for 12 weeks. Frequency of appearance and severity of clinical symptoms and signs of associated diseases, serum immunoglobulin concentrations and balance of pro-oxidant and antioxidant biomarkers were recorded at treatment initiation and one month after treatment completion. Therapeutic response was defined as complete, partial, stable disease or progressive disease. Descriptive statistics and significance were calculated to compare groups and assess effect size. RESULTS: One month after treatment completion, 70% of patients in the experimental group experienced significant increases in IgG(p = 0.000) and IgM (p = 0.033). The experimental group also displayed decreased pro-oxidation biomarkers, glutathione modulation and increased antioxidant enzymes, with reduced oxidative stress; none of these occurred in the control group. Complete therapeutic response was achieved in 85% of patients in the experimental group and only 45% in the control group. Mild, transient adverse events were reported in both groups. CONCLUSIONS: Ozone therapy by rectal insufflation is a suitable therapeutic option for treating IgA deficiency because it produces antioxidant and immunomodulatory effects and is feasible, safe and minimally invasive. CONTRIBUTION OF THIS RESEARCH: This paper introduces in Cuba a new treatment a for IgA deficiency, with immunomodulatory and antioxidant effects offering substantial clinical benefits to patients with this immunodeficiency.

Aspectos generales de algunas entidades dentro de los síndromes linfoproliferativos crónicos: La leucemia linfoide crónica / General aspects of some entities within chronic lymphoproliferative syndromes: chronic lymphocytic leukemia

La leucemia linfoide crónica es el tipo de leucemia más común en los países occidentales, afecta con mayor frecuencia al sexo masculino, con una edad promedio al diagnóstico de 65 años. La variedad más frecuente es la de estirpe B; comprenden un grupo de neoplasias biológicamente diferentes, caracterizadas por una proliferación y acúmulo de linfocitos pequeños de apariencia madura en sangre periférica, médula ósea y tejidos linfoides. Es el prototipo de enfermedad maligna que involucra a defectos de la muerte celular programada o apoptosis. Esta enfermedad puede presentar variaciones en sus características inmunofenotípicas, clínicas, citogenéticas y moleculares. Aproximadamente, el 80 por ciento de los pacientes con leucemia linfoide crónica B presentan anormalidades cromosómicas, principalmente: deleciones de los cromosomas 11,13, 6,14 y 17, estas tres últimas de mal pronóstico. Pueden presentar además, disfunciones inmunes responsables de inmunodeficiencia y autoinmunidad. Se desconoce la causa de esta enfermedad aunque los informes iniciales sugieren la implicación de los genes Bcl-1 y Bcl-2, es por eso que la terapia actual está dirigida a la inhibición de Bcl-2 por ser el responsable en la regulación de la apoptosis(AU)

Chronic lymphoid leukemia is the most common type of leukemia in Western countries, which most often affects males and the average age at diagnosis is 65 years. The most common form is the B-cell and is described in this article. LLC comprise a biologically distinct group of neoplasms characterized by proliferation and accumulation of small mature lymphocytes appearance in peripheral blood, bone marrow and tissues linfoides. Is the prototype of malignant disease involving defects programmed cell death or apoptosis. This disease may present variations in their immunophenotypic, clinical, cytogenetic and molecular characteristics. Approximately 80 percent of patients with B-CLL have chromosomal abnormalities, mainly: deletions of chromosomes 11, 13, 6, 14 and 17. These last three are bad prognosis. The patients with CLL may have also immune dysfunctions responsible for immunodeficiency and autoimmunity. It is unknown the cause of CLL although initial reports suggest the involvement of Bcl-1 and Bcl-2 gene is why the current therapy is directed to inhibition of Bcl-2 as this is responsible in regulating apoptosis(AU)

Expresión del antígeno CD45 en la Leucemia Linfoide Aguda Pediátrica / Evaluation of CD45 antigen expression in acute lymphoblastic leukemia

Introducción: la leucemia linfoide aguda (LLA) es la neoplasia más frecuente en la infancia. La determinación del antígeno CD45 discrimina entre los blastos y las células reactivas en la médula ósea (MO). Objetivo: evaluar la expresión del antígeno CD45 sobre los blastos de pacientes con LLA, según los distintos subtipos inmunológicos, su posible relación con las características biológicas y clínicas de presentación de la enfermedad y la respuesta al tratamiento antileucémico. Métodos: se estudiaron 150 pacientes con LLA procedentes de varios servicios oncohematológicos del país, entre enero del 2008 y mayo del 2015. El inmunofenotipaje celular de la MO se realizó por citometría de flujo. Resultados: el antígeno CD45 mostró una gran heterogeneidad de expresión sobre los linfoblastos. Del total de enfermos estudiados, 19,3 por ciento no expresaron sobre los blastos el antígeno CD45, 36,7 por ciento presentaron una expresión moderada y 44 por ciento mostraron una alta densidad de expresión. Se encontró diferencia significativa al comparar el fenotipo leucémico con la expresión del antígeno CD45 sobre los blastos (p = 0,000). Ningún enfermo presentó adenopatías mediastinales, con diferencias significativas (p = 0,000), según el fenotipo y la expresión de CD45. Los pacientes con LLA-T cuyos blastos no expresaron CD45 tuvieron una mala respuesta al tratamiento anti-leucémico los días 8 y 15 en sangre periférica y MO, respectivamente. Conclusión: la expresión de CD45 sobre los blastos, pudiera ser considerada como un factor pronóstico adicional para la estratificación en diferentes grupos de riesgos, de la LLA en el niño(AU)

Introduction: Acute lymphoblastic leukemia (ALL) is the most frequent neoplasia in infancy. Determination of CD45 antigen discriminates between blasts and reactive cells in the bone marrow (MO). Objective: To evaluate the expression of the CD45 antigen on the blasts of patients with ALL, according to the different immunological subtypes, their possible relation with the biological and clinical characteristics of the disease and the response to antileukemic treatment. Methods : 150 patients with ALL were studied from various onco-hematological services of the country, between January 2008 and May 2015. The cellular immunophenotyping of the MO was performed by flow cytometry. Results : The CD45 antigen showed a great heterogeneity of expression on the lymphoblasts. Of the total number of patients studied, 19.3 percent did not express the CD45 antigen on the blasts, 36.7 percent presented moderate expression and 44 percent showed a high expression density of it.A significant difference was found when comparing the leukemic phenotype with the expression of the CD45 antigen on the blasts (p = 0.000). No patient had mediastinal lymphadenopathy, with significant differences (p = 0.000), according to the phenotype and CD45 expression. Patients with T-ALL whose blasts did not express CD45 had a poor response to anti-leukemic treatment on days 8 and 15 in peripheral blood and MO, respectively. Conclusion: CD45 expression on blasts could be considered as an additional prognostic factor for stratification in different risk groups of ALL in children(AU)