Effect of Cuban Porcine Pulmonary Surfactant (Surfacen) and rCmPI-II Protease Inhibitor on Neutrophil Elastase Activity.

INTRODUCTION: In inflammatory respiratory diseases, the imbalance between proteases and endogenous protease inhibitors leads to an exacerbated activity of human neutrophil elastase (a protease that destroys the extracellular matrix and stimulates proinflammatory cytokine release). Elastase is considered a target in the search for therapeutic treatments for inflammatory respiratory diseases. Pulmonary surfactant is a promising product for this purpose, because in addition to its biophysical function, it has anti-inflammatory properties. OBJECTIVE: Evaluate effect of the Cuban porcine pulmonary surfactant (Surfacen), the rCmPI-II elastase inhibitor, and the Surfacen/rCmPI-II combination on activated neutrophil elastase activity in vitro, and determine if Surfacen's interface property changes in the presence of the inhibitor. METHODS: The anti-elastase effect of Surfacen, rCmPI-II and the Surfacen/rCmPI-II combination was evaluated in an in vitro model of activated neutrophils, previously purified from the blood of healthy subjects. The cells were stimulated with LPS/fMLP and were incubated with different concentrations of Surfacen, rCmPI-II and the Surfacen/rCmPI-II combination. Elastase activity was measured. The interface property was determined on a Langmuir surface balance. The new index, called the abdominal adipose deposit index, was obtained by multiplying the subcutaneous fat thickness by visceral fat thickness, both measured by ultrasound. A cutoff point was established that facilitated discernment of an unhealthy phenotype: normal weight but metabolically obese, a cardiometabolic risk factor. RESULTS: Surfacen at 10 mg/mL inhibited 71% of stimulated neutrophil elastase activity. rCmPI-II at 0.1 µM reduced 20% of elastase activity; at 200 µM-the maximum concentration evaluated-inhibition was 68%. Both products had a dose-dependent effect. The Surfacen/inhibitor combination (0.5 mg/mL/80 µM) did not affect the surfactant interface property or the inhibitory activity of rCmPI-II against human neutrophil elastase. CONCLUSIONS: Surfacen and the rCmPI-II inhibitor have an anti-elastase effect on an activated neutrophil model. rCmPI-II does not affect Surfacen's interface property and, therefore, both can be evaluated for combined use in treating inflammatory lung diseases.

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.

Riesgo de complicaciones virales postrasplante en candidatos a trasplante renal con donante vivo / Risk of viral post-transplant complications in living donor kidney transplant candidates

Introducción: El trasplante renal con donante vivo se promueve en Cuba y en el resto del mundo. La definición del riesgo de complicaciones postrasplante por citomegalovirus (CMV) y virus de Epstein Barr (EBV) es parte de las pruebas de compatibilidad pretrasplante. Objetivo: Determinar el riesgo de complicaciones postrasplante con estos virus en pacientes cubanos candidatos a trasplante renal con donante vivo. Método: Se determinaron anticuerpos IgG anti-CMV e IgG anti-EBV por ensayo de inmunoabsorción ligado a enzima en 301 muestras de candidatos a TRDV y 390 de posibles donantes recibidas, entre julio de 2013 y julio de 2019, en el laboratorio de Histocompatibilidad del Instituto de Hematología e Inmunología. Resultados: En los candidatos a trasplante renal con donante vivo la seroprevalencia del EBV fue mayor que la del CMV y ambas aumentaron con la edad. El 100 % de los pacientes de grupo sanguíneo AB tuvieron EBV y CMV. No existió dependencia entre los anticuerpos anti-EBV y anti-CMV con los anticuerpos anti-HLA, la edad, sexo, color de la piel, grupo sanguíneo, hepatitis B y C, tipo de diálisis, trasplantes y transfusiones previas. El 7,3 % de los pacientes presentaron alto riesgo de complicaciones postrasplante. Conclusiones: La seroprevalencia de CMV y EBV en los candidatos a trasplante renal con donante vivo cubanos es alta, por lo que pocos tienen riesgo alto de complicaciones postrasplantes debido a estos virus(AU)

Introduction: Living donor kidney transplant is promoted in our country and the rest of the world. The definition of Cytomegalovirus (CMV) and Epstein Barr virus (EBV) post-transplant complications risk is part of pretransplant compatibility tests. Objective: To assess post-transplant complication risk with these viruses in Cuban candidates to living donor kidney transplant. Methods: Detection of IgG anti-CMV and IgG anti-EBV antibodies by enzyme-linked immunoabsorbent assay was performed on 301 receptors and 390 living donors' serum examples received, from July 2013 to July 2019, at the Histocompatibility department of the Institute of Hematology and Immunology. Results: In candidates to living donor kidney transplant, EBV seroprevalence was greater than CMV's and increased with age. The 100% of AB blood group had CMV and EBV. There was no association between IgG anti-CMV and IgG anti-EBV antibodies and anti-HLA antibodies, age, gender, skin color, blood group, hepatitis B and C, dialysis type, previous transplants, and transfusions. The 7.3% of patients were labeled as post-transplant complications high risk. Conclusions: The seroprevalence of CMV and EBV in living donor kidney transplant Cuban candidates is high, that´s why patients with high risk for post-transplant complications due to these viruses are a few(AU)

Anticuerpos anticitomegalovirus y antivirus de Epstein Barr en pacientes cubanos / Anti-cytomegalovirus and anti-Epstein Barr virus antibodies in Cuban patients

Introducción: La infección por el virus de Epstein-Barr es la causa más frecuente de la mononucleosis infecciosa. El citomegalovirus es la segunda causa de síndrome por mononucleosis y presenta gran morbimortalidad en pacientes inmunodeprimidos trasplantados de órganos sólidos, médula ósea e infección por el virus de la inmunodeficiencia humana. Objetivo: Determinar la seroprevalencia de anticuerpos anticitomegalovirus y anti-Epstein-Barr en pacientes cubanos. Métodos: Se realizó la detección de anticuerpos IgM e IgG frente a ambos virus, por ensayo de inmunoabsorción ligado a enzima, a las muestras de pacientes con diagnóstico de infecciones, síndromes febriles, adenopatías a repetición, entre otros, que arribaron al departamento de Histocompatibilidad del Instituto de Hematología e Inmunología de enero 2017 a junio de 2020. Resultados: Se estudiaron 892 muestras de todo el país. La seroprevalencia de anticuerpos IgG anti-citomegalovirus fue 81,62 por ciento y 82,06 por ciento para IgG anti-Epstein-Barr. La seroprevalencia con ambos virus en menores de 20 años fue elevada y aumentó con la edad. La infección primaria de estos virus se detectó principalmente en los menores de 20 años. Conclusiones: La seroprevalencia de la infección por ambos virus en la población estudiada concuerda con lo referido en la literatura en sujetos sanos(AU)

Introduction: Epstein-Barr virus infection is the most frequent cause of infectious mononucleosis. Cytomegalovirus is the second cause of mononucleosis syndrome and presents great morbidity and mortality in immunosuppressed patients, mainly in transplanted patients and in those with human immunodeficiency virus infection. Objective: To determine the seroprevalence of anti-cytomegalovirus and anti-Epstein-Barr antibodies in Cuban patients. Materials and methods: The detection IgG and IgM antibodies against both viruses was done by Enzyme linked immunosorbent assay to infection, febrile syndrome, repeated adenopathies and others diagnosis patient´s samples that arrived to the Histocompatibility Department of the Institute of Hematology and Immunology from January 2017 to June 2020. Results: 892 serum samples from patients from all over the country were studied. The seroprevalence of anti-cytomegalovirus IgG antibodies in the studied sample was 81.62 percent and 82.06 percent for anti-Epstein-Barr. The seroprevalence for both viruses below 20 years old age was high and increased with age. Primary infection with the viruses was detected mainly below 20 years age. Conclusions: The seroprevalence of the infection of both viruses in the studied population agrees with what is reported in the literature(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.

Caracterización inmunogenética de donantes cadavéricos cubanos en el año 2019 / Immunogenetic characterization of Cuban cadaveric donors in 2019

Introducción: El trasplante es la opción terapéutica más favorable para las personas con insuficiencia renal crónica. El donante puede ser cadavérico o donante vivo, emparentado o no. Los resultados del trasplante están en relación con varios factores inmunológicos y no inmunológicos. Objetivo: Caracterizar inmunogenéticamente a los donantes cadavéricos cubanos para trasplante renal. Métodos: Se realizó un estudio transversal y descriptivo de los donantes cadavéricos durante el año 2019. Se analizó la región de procedencia, sexo, color de la piel y rangos de edades de los donantes, así como, grupo sanguíneos ABO y Rhesus Rh; serología para VIH, Virus de hepatitis B(VHB) y Virus de hepatitis C (VHC); y hábitos tóxicos. Resultados: Se estudió un total de 95 donantes cadavéricos, 62 provenientes del occidente y 33 del centro del país. El 63,2 por ciento fueron masculinos y 36,8 por ciento femenino. El grupo de edad de mayor frecuencia fue 40 - 60 años y la edad media de 49,45 años. El 58,95 por ciento de los pacientes fueron de grupo sanguíneo O; 30,53 por ciento grupo A y los grupos B y AB tuvieron 5,26 por ciento de prevalencia; y solo 8 fueron Rh negativos. Todos tuvieron serología para VIH, VHB y VHC negativas. Las enfermedades asociadas más frecuentes fueron la hipertensión arterial y la diabetes mellitus. Conclusiones: Los donantes cadavéricos durante el año 2019 mostraron características similares a las reportadas por otros estudios. El aumento de las edades de los donantes incide en la aparición de enfermedades asociadas y esto pudiera repercutir en el resultado del trasplante(AU)

Introduction: Transplantation is the most favorable therapeutic option for people with chronic renal failure. The donor can be a cadaveric or living donor, related or not. Transplant outcomes are related to various immunological and non-immunological factors. Objective: To characterize Cuban cadaveric donors for renal transplantation Materials and methods: A cross-sectional and descriptive study of cadaveric donors was carried out during the year 2019. The region of origin, sex, skin color and age ranges of the donors were analyzed, as well as ABO and Rhesus Rh blood groups; serology for HIV, Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV), and toxic habits. Results: A total of 95 cadaveric donors were studied, 62 from the West and 33 from the Center of the country. 63.2 percent were male and 36.8 percent female due to the most frequent age group being 40-60 years and the mean age of 49.45 years. 58.95 percent of the patients were of blood group O, 30.53 percent group A and groups B and AB had 5.26 percent prevalence; and only 8 were Rh negative. All had negative serology for HIV, HBV and HCV. The most frequent associated diseases were arterial hypertension and diabetes mellitus. Conclusions: The cadaveric donors during the year 2019 showed characteristics similar to those reported by other studies. The increase in the age of the donors affects the appearance of associated diseases and this could affect the result of the transplant(AU)

Supervivencia del trasplante renal en relación con la compatibilidad inmunológica en Cuba / Kidney transplant survival in relation to immunological compatibility in Cuba

RESUMEN Introducción: El trasplante renal es uno de los métodos de sustitución de la función renal y tiene como factor de mayor influencia en su supervivencia, la compatibilidad inmunológica. Objetivo: Definir la supervivencia del trasplante y su relación con el grado de compatibilidad. Material y Métodos: Estudio retrospectivo, del tiempo de supervivencia con base hospitalaria, de los 827 pacientes trasplantados entre los nueve centros del país, en el quinquenio 2015-2019. Para estimar las curvas de supervivencias se empleó el Método de Kaplan Meier, por el SPSS 22.0. Resultados: Supervivencia del injerto al año 72,9 % y paciente 89,0 %, con media de sobrevida de los injertos de 3,6 años y del paciente de 4,6. Para los pacientes con dos y más compatibilidad, la supervivencia del injerto al año fue mayor, 77,0 % v/s 69,2 % y menos, para el resto. Posterior al año, también son diferentes las supervivencias por grado de compatibilidad. El rechazo agudo inmunológico, que es una de las principales causas de pérdidas de injertos, tiene mucho mayor incidencia en los trasplantados sin compatibilidad que en los compatibles (17,4 % v/s 9,9 %). Para las causas de muerte de los pacientes, la infección fue la predominante, y muy significativo para los que no comparten compatibilidad v/s los que sí (56,9 % v/s 31,9 %). Conclusiones: La compatibilidad inmunológica entre donante y receptor, propicia diferencia en las supervivencias de injertos y pacientes, siendo mejor mientras más compatibles sean el donante y el receptor.

ABSTRACT Introduction: Kidney transplant is one of the methods of kidney function replacement, and immunological compatibility is the most important factor influencing survival. Objective: To define transplant survival and its relationship with the degree of compatibility. Material and Methods: Hospital-based retrospective study of survival time of the 827 transplanted patients in the nine centers of the country during the five-year period (2015 - 2019). The Kaplan Meier method was used to estimate the survival curves, using SPSS version 22.0. Results: The graft survival was 72,9 % and the patient survival was 89,0 % in the first year; the mean graft survival was 3,6 years, and the patient survival was 4,6 years. For patients with two and more compatibilities, graft survival was significantly higher in the first year (77,0 % versus 69,2 %), but it was lower for the rest. One year after, the survival rates related to the degree of compatibility are also different. Acute immune rejection, which is one of the main causes of graft loss, has a much higher incidence among the transplanted patients without compatibility than in the compatible ones (17,4 % versus 9,9 %). Infection was the predominant cause of death in these patients, which was incredibly significant in those who do not share compatibility as opposed to those who do share it (56,9 % versus 31,9 %). Conclusions: Immunological compatibility between donor and recipient results in differences between graft and patient survival rates, so the more compatibility between the donor and the recipient, the higher the survival rate.

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.

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.

Reconstrucción mamaria poscáncer en el Instituto Nacional de Oncología y Radiobiología de Cuba / Post-cancer breast reconstruction at the National Institute of Oncology and Radiobiology of Cuba

INTRODUCCIÓN Y OBJETIVO: El tratamiento quirúrgico del cáncer de mama ocasiona secuelas deformantes que repercuten negativamente en las pacientes. La reconstrucción mamaria es la etapa culminante de este tratamiento. En el Instituto Nacional de Oncología y Radiobiología (INOR) de La Habana, Cuba, se viene realizando con mayor frecuencia este proceder; por lo que nos propusimos caracterizar la reconstrucción mamaria en dicha institución. MATERIAL Y MÉTODO: Estudio ambispectivo en el Servicio de Cirugía Reconstructiva del Instituto Nacional de Oncología y Radiobiología de Cuba entre 2013 y 2017. La investigación incluyó 192 pacientes de las que recogimos variables demográficas y oncorreconstructivas. RESULTADOS: Se realizaron una media de 38.4 cirugías anuales con un promedio de edad de las pacientes de 45.3 años. El 56.6% presentó mastectomía de Madden y el 34.4% se reconstruyó con técnicas ahorradoras de tejidos. El carcinoma ductal infiltrante se diagnosticó en 183 mujeres, el 38% presentó un cáncer en estadio II. La reconstrucción inmediata predominó en el 55.5% de las cirugías, en el 48.4% se utilizó la expansión tisular y en el 77.6% no se presentaron complicaciones. El cáncer en estadio III presentó una odds ratio (OR) estadísticamente significativa de 3.04 para las complicaciones posquirúrgicas. CONCLUSIONES: La reconstrucción mamaria en el periodo estudiado se comportó de forma similar a estudios anteriores en el INOR; sin embargo, evidenciamos un aumento de la reconstrucción inmediata con técnicas conservadoras de mama y ahorradoras de piel y un incremento de las pacientes reconstruidas mayores de 50 años. Se presentaron pocas complicaciones y no identificamos factores de riesgo para la recidiva y el fallecimiento. Las pacientes con cáncer en estadio III presentaron un incremento de las complicaciones posquirúrgicas de la reconstrucción mamaria

BACKGROUND AND OBJECTIVE: Surgical treatment of breast cancer causes deforming sequelae that have a negative impact on patients. Breast reconstruction constitutes the culminating stage of this treatment. At the National Institute of Oncology and Radiobiology (INOR) of La Habana, Cuba, this procedure has been performed more frequently; therefore, we proposed to characterize breast reconstruction in this institution. METHODS: An ambispective study was carried out in the Reconstructive Surgery Service of the National Institute of Oncology and Radiobiology of Cuba from 2013 to 2017, with the aim of characterizing breast reconstruction. The research included 192 patients. Demographic and onco-reconstructive variables were collected. RESULTS: An average of 38.4 surgeries were performed annually with an average age of 45.3 years. A Madden mastectomy was performed in 56.6% and 34.4% were reconstructed with tissue-sparing techniques. Infiltrating ductal carcinoma was diagnosed in 183 women, 38% presented stage II cancer. Immediate reconstruction predominated in 55.5% of the surgeries, tissue expansion was used in 48.4% and in 77.6% there were no complications. Stage III cancer presented a statistically significant odds ratio (OR) of 3.04 for postoperative complications. CONCLUSIONS: Breast reconstruction behaved similarly to previous studies at INOR, however, there was an increase in immediate reconstruction with breast-conserving and skin-sparing techniques, and an increase in reconstructed patients over 50 years of age. There were few complications and no risk factors for recurrence and death were identified

Reconstrucción mamaria con el uso expansores tisulares / Breast reconstruction with the use of tissue expanders

RESUMEN Introducción: La reconstrucción mamaria por cáncer, mediante la técnica de expansión tisular es una técnica que proporciona piel de color, textura y sensibilidad naturales. Objetivo: Caracterizar la reconstrucción mamaria con el uso de expansores tisulares en el Instituto Nacional de Oncología y Radiobiología de Cuba. Método: Se realizó un estudio retrospectivo y longitudinal en el Servicio de Cirugía Reconstructiva del Instituto Nacional de Oncología y Radiobiología de Cuba del 2013 al 2017. La muestra de 93 pacientes se seleccionó de forma consecutiva del universo de pacientes. El análisis estadístico incluyó las pruebas de Chi-cuadrado, estimación de la razón de momios y regresión logística binaria, con nivel de significación p ≤ 0,05. Resultados: Predominó la reconstrucción en mujeres con un promedio de edad de 45,7 años, [IC95 por ciento (43,8-47,5) y desviación estándar 9.0]. La quimioterapia se administró a 74 pacientes y la radioterapia a 41. La reconstrucción diferida se realizó en el 51,6 por ciento de las cirugías, y en el 72,0 por ciento no se presentaron complicaciones. El cáncer en estadio III y el uso de quimioterapia y radioterapia neoadyuvante mostraron riesgo con significación estadística para las complicaciones posquirúrgicas. Conclusiones: La reconstrucción mamaria mediante el uso de expansores tisulares presentó características demográficas y clínicas similares a las descritas previamente en la población cubana y el resto del mundo, aunque con peculiaridades desde el punto de vista onco-reconstructivo. La realización de la cirugía reconstructiva inmediata luego de la radioterapia neoadyuvante resultó en un mayor riesgo de complicaciones(AU)

ABSTRACT Introduction: Breast reconstruction for cancer, using the tissue expansion technique, is a technique that provides skin of natural color, texture and sensitivity. Objective: To characterize breast reconstruction with the use of tissue expanders at the National Institute of Oncology and Radiobiology of Cuba. Method: A retrospective and longitudinal study was carried out in the Reconstructive Surgery Service of the National Institute of Oncology and Radiobiology of Cuba from 2013 to 2017. The sample of 93 patients was selected consecutively from the universe of patients. Statistical analysis included Chi-square tests, estimation of the odds ratio and binary logistic regression, with a significance level of p ≤ 0,05 Results: Reconstruction predominated in women with an average age of 45.7 years, [95 percent CI (43.8-47.5) and standard deviation 9.0]. Chemotherapy was administered to 74 patients and radiotherapy to 41. Delayed reconstruction was performed in 51.6 percent of the surgeries, and in 72.0 percent there were no complications. Stage III cancer and the use of neoadjuvant chemotherapy and radiotherapy showed a statistically significant risk for postoperative complications. Conclusions: Breast reconstruction by using tissue expanders presented demographic and clinical characteristics similar to those previously described in the Cuban population and the rest of the world, although with peculiarities from the onco-reconstructive point of view. Performing immediate reconstructive surgery after neoadjuvant radiation therapy resulted in an increased risk of complications(AU)

Caracterización de los anticuerpos anti-HLA en posibles receptores cubanos de trasplante cardiaco / Characterization of anti-HLA antibodies in Cuban possible receptors of heart transplant

Introducción: En la supervivencia del corazón trasplantado son de importancia el empleo de los anticuerpos contra el sistema principal de histocompatibilidad (anticuerpos anti-HLA). Hace seis años se introdujo en Cuba el porcentaje de anticuerpos anti-HLA frente a panel (PRA) por método de ensayo de inmunoabsorción ligado a enzima (ELISA) como parte de las pruebas de compatibilidad pretrasplante de los receptores de trasplante cardiaco. Objetivo: Caracterizar los anticuerpos anti-HLA en pacientes receptores cubanos de trasplante cardiaco. Métodos: Entre septiembre de 2013 y abril de 2017 se les realizó el PRA por ELISA a 38 muestras de pacientes recibidas en el laboratorio de histocompatibilidad del Instituto de Hematología e Inmunología. Se utilizó la comparación de proporciones para el análisis estadístico. Resultados: El 47,4 por ciento de los pacientes estudiados presentó anticuerpos anti-HLA, fueron los más frecuentes los de clase I. La proporción de pacientes con PRA del 0 por ciento fue mayor en PRA clase II que en I (p: 0,0027). Mientras que fue mayor la proporción de pacientes con PRA clase I entre el 20 y el 75 por ciento (p: 0,0046). El 77,8 por ciento de los pacientes tuvo un PRA clase I mayor al 10 por ciento y en el PRA clase II alcanzó el 80 por ciento. Conclusiones: El porcentaje de anticuerpos anti-HLA frente a panel por método de ensayo de inmunoabsorción ligado a enzima permitió una mejor caracterización de los anticuerpos anti-HLA, lo que contribuyó a mejorar la compatibilidad en este tipo de paciente(AU)

Introduction: In survival after heart transplantation, the use of antibodies against the main histocompatibility system (anti-HLA antibodies) is important. Six years ago, the percentage of anti-HLA antibodies against panel (PRA) by enzyme-linked immunosorbent assay (ELISA) method was introduced in Cuba as part of the pre-transplant compatibility tests of heart transplant recipients. Objective: To characterize anti-HLA antibodies in Cuban heart transplant recipients. Methods: Between September 2013 and April 2017, PRA by ELISA was performed on 38 patient samples received in the histocompatibility laboratory of the Institute of Hematology and Immunology. Comparison of proportions was used for statistical analysis. Results: 47.4 percent of the study patients presented anti-HLA antibodies; those in class were the most frequent. The proportion of patients with PRA of 0 percent was higher in PRA class II than in class I (p=0.0027). The proportion of patients with PRA class I was greater, accounting for 20-75 percent (p=0.0046). 77.8 percent of the patients had a class I PRA greater than 10 percent, while in class II PRA it reached 80 percent. Conclusions: The percentage of anti-HLA antibodies versus a panel of enzyme linked immunosorbent assay method allowed better characterization of anti-HLA antibodies, which contributed to improving compatibility in this type of patient(AU)

Polimorfismo de los antígenos leucocitarios humanos en receptores cubanos de trasplante relacionado de progenitores hematopoyéticas / Polymorphism of human leukocyte antigens in Cuban recipients of related hematopoietic stem cell transplants

Introducción: El trasplante relacionado de células progenitoras hematopoyéticas (TCPH) es una alternativa terapéutica curativa para los pacientes con ciertos tipos de hemopatías o de inmunodeficiencias, en la que se selecciona como donante a un familiar del receptor. Objetivo: Caracterizar el sistema de antígenos leucocitarios humanos (HLA) en receptores de TCPH relacionado. Métodos: Se realizó un estudio descriptivo y transversal en el departamento de Histocompatibilidad del Instituto de Hematología e Inmunología desde enero 2013 hasta diciembre de 2015. Se tipificaron 75 genes HLA mediante la técnica de reacción en cadena de la polimerasa con cebadores de secuencia específico, de baja resolución a 117 pacientes con criterio de TCPH. Para el análisis inmunogenético se empleó el programa Arlequín 3.5.2.2. Resultados: Fueron más frecuentes los genes HLA-A*02, HLA-B*35, HLA-DQB1*03, HLA-DRB1*03 y HLA-DRB1*04, los haplotipos de dos loci HLA-A*02 B*35, HLA-DQB1*03 DRB1*04 y el haplotipo extendido HLA-A*03 B*07 DQB1*06 DRB1*15. Conclusiones: Los genes del sistema HLA en pacientes cubanos candidatos a TCPH relacionado presentaron frecuencias similares a las descritas en poblaciones generales de Cuba y el mundo, aunque con características distintivas en algunos genes y haplotipos(AU)

Introduction: Related hematopoietic progenitor cell (TCPH) transplantation is a curative therapeutic alternative for patients with certain types of hemopathies or immunodeficiencies, in which a recipient family member is selected as a donor. Objective: To characterize the human leukocyte antigen (HLA) system in related TCPH receptors. Methods: A descriptive and cross-sectional study was conducted in the Histocompatibility department of the Institute of Hematology and Immunology from January 2013 to December 2015. 75 HLA genes were typed using the polymerase chain reaction technique with specific sequence primers, from Low resolution to 117 patients with TCPH criteria. For the immunogenetic analysis, the Harlequin 3.5.2.2 program was used. Results: The genes HLA-A * 02, HLA-B * 35, HLA-DQB1 * 03, HLA-DRB1 * 03 and HLA-DRB1 * 04, the haplotypes of two HLA-A * 02 B * 35 loci were more frequent , HLA-DQB1 * 03 DRB1 * 04 and the extended haplotype HLA-A * 03 B * 07 DQB1 * 06 DRB1 * 15. Conclusions: The genes of the HLA system in Cuban patients related to TCPH presented frequencies similar to those described in general populations of Cuba and the world, although with distinctive characteristics in some genes and haplotypes(AU)