Hepatotoxicity as dose-limiting toxicity of the combination of bosutinib and atezolizumab in patients with chronic myeloid leukemia. Results of the ZEROLMC study.

In the field of chronic myeloid leukemia (CML), new strategies are needed to increase the rate of successful treatment discontinuations, a crucial goal in this disease. Anti-PD-L1 checkpoint inhibitors are a promising therapeutic approach in CML after the demonstration of an increase of these inhibitory molecules in patients with CML. A phase Ib/II (NCT04793399, registration date March 11, 2021) open-label exploratory trial has been conducted to evaluate the safety of atezolizumab, a humanized anti-PD-L1 antibody, in combination with bosutinib in patients with newly diagnosed chronic phase CML. A total of 36 patients were planned to be enrolled, but the study had to be prematurely terminated due to safety concerns. Nine patients were included in the study, and only 8 went on to receive the combination with atezolizumab. There were a total of 44 adverse events (AEs) during the study period. The most frequent were gastrointestinal (50%), mostly mild (86% grade 1-2). The most serious AEs were hepatic. There were 17 hepatic AEs in 5 patients. Of the hepatic AEs 5 were during the bosutinib monotherapy phase and 12 during the combination phase (AST increase x4, ALT increase x4, blood bilirubin increase x1, alkaline phosphatase elevation x2, GGT increase x2), most of them grade 3-4. There were 2 patients who presented a dose-limiting toxicity; a grade 3 elevation of transaminases, that led to premature termination of the study. The combination of atezolizumab with bosutinib presents hepatotoxicity as a dose-limiting effect and therefore we do not recommend to explore this combination in future studies.

Estilos y enfoques de aprendizaje en estudiantes de Estomatología y relación con el rendimiento académico en Farmacología

Fundamento: los estilos y enfoques de aprendizaje permiten conocer cómo el estudiante enfrenta este proceso y el modo en que procesa la información que debe ser asimilada. Objetivo: identificar los estilos y enfoques de aprendizaje que utilizan estudiantes de Estomatología y su relación con el rendimiento académico en la disciplina Farmacología. Métodos: estudio descriptivo-transversal, con enfoque cualicuantitativo, realizado de noviembre 2021 a enero 2022. La muestra, no probabilística, fue de 28 estudiantes (90,3 %) de segundo año de la carrera de Estomatología impartida en la Facultad de Estomatología de La Habana. A los participantes se les aplicaron dos instrumentos: cuestionario Honey y Alonso sobre estilos de aprendizaje y cuestionario Enfoques e Inventario de Habilidades de Estudio de los Estudiantes. Las dimensiones del rendimiento académico fueron excelente, bueno, y regular. Resultados: predominó la preferencia muy alta/alta en el estilo teórico (67,86 %) y la preferencia moderada en el reflexivo (67,86 %). Se encontró relación significativa entre la cantidad de estilos de aprendizaje de preferencia muy alta/alta y el rendimiento académico (p=0,044), y entre el estilo reflexivo y el rendimiento académico (p=0,024). También, se encontró relación significativa entre el rendimiento académico y el enfoque de aprendizaje estratégico (p=0,008) y la preferencia por la transmisión de la información (p=0,028). Conclusiones: en los estudiantes existen estilos y enfoques de aprendizaje que se relacionan con el rendimiento académico en Farmacología; se muestran aspectos que se deben considerar para el mejoramiento del proceso docente de esta disciplina en Estomatología.

Foundation: the learning styles and approaches allow us to know how the student faces this process and the way in which they process the information that must be assimilated. Objective: to identify the learning styles and approaches used by Dentistry students and their relationship with academic performance in the Pharmacology discipline. Methods: a descriptive-cross-sectional study, with a qualitative-quantitative approach, carried out from November 2021 to January 2022. The non-probabilistic sample consisted of 28 students (90.3%) in the second year of the Dentistry course taught at the Havana Dentistry Faculty. Two instruments were applied to the participants: the Honey and Alonso questionnaire on learning styles and the Approaches and Inventory of Student Study Skills questionnaire. The dimensions of academic performance were excellent, good, and regular. Results: the very high/high preference predominated in the theoretical style (67.86%) and the moderate preference in the reflective style (67.86%). A significant relationship was found between the number of very high/high preference learning styles and academic performance (p=0.044), and between the reflective style and academic performance (p=0.024). Also, a significant relationship was found between academic performance and the strategic learning approach (p=0.008) and the preference for the transmission of information (p=0.028). Conclusions: there are learning styles and approaches among students that are related to academic performance in Pharmacology; Aspects that should be considered for the improvement of the teaching process of this discipline in Dentistry are shown.

Trap and ambush therapy using sequential primary and tumor escape-selective oncolytic viruses.

In multiple models of oncolytic virotherapy, it is common to see an early anti-tumor response followed by recurrence. We have previously shown that frontline treatment with oncolytic VSV-IFN-ß induces APOBEC proteins, promoting the selection of specific mutations that allow tumor escape. Of these mutations in B16 melanoma escape (ESC) cells, a C-T point mutation in the cold shock domain-containing E1 (CSDE1) gene was present at the highest frequency, which could be used to ambush ESC cells by vaccination with the mutant CSDE1 expressed within the virus. Here, we show that the evolution of viral ESC tumor cells harboring the escape-promoting CSDE1C-T mutation can also be exploited by a virological ambush. By sequential delivery of two oncolytic VSVs in vivo, tumors which would otherwise escape VSV-IFN-ß oncolytic virotherapy could be cured. This also facilitated the priming of anti-tumor T cell responses, which could be further exploited using immune checkpoint blockade with the CD200 activation receptor ligand (CD200AR-L) peptide. Our findings here are significant in that they offer the possibility to develop oncolytic viruses as highly specific, escape-targeting viro-immunotherapeutic agents to be used in conjunction with recurrence of tumors following multiple different types of frontline cancer therapies.

Infección por SARS-CoV-2 y grupos sanguíneos en pacientes cubanos diagnosticados con la COVID-19 / SARS-Cov-2 Infection and Blood Groups in Cuban Patients Diagnosed with COVID-19

Introducción: Diferentes estudios han propuesto la relación entre los grupos sanguíneos del sistema ABO y la susceptibilidad a la COVID-19 y su importancia en el curso de la enfermedad. Objetivo: Determinar la frecuencia fenotípica de grupos sanguíneos ABO y RhD en un grupo de pacientes con infección activa por SARS-CoV-2. Métodos: Se realizó un estudio descriptivo, transversal y caso control en el Hospital Docente Clínico Quirúrgico Freyre Andrade de La Habana, para determinar la frecuencia fenotípica ABO y RhD en un grupo de pacientes con enfermedad activa por la COVID-19. Se estudiaron 928 muestras de sangre de pacientes con diagnóstico de COVID-19 y 1050 muestras pertenecientes a individuos sanos como grupo control. El grupo sanguíneo ABO y RhD se determinó por método de aglutinación en tubo con sueros hemoclasificadores anti-A, anti-B, anti-A+B, yanti-D. Los resultados fueron expresados en frecuencias absolutas y relativas y se determinó la asociación del grupo sanguíneo con la gravedad de la enfermedad por medio de la prueba no paramétrica de χ2 con un nivel de significación de p ≤ 0,05. Resultados: Se observó predominio del fenotipo O (49,24 por ciento) seguido del A (35,79 por ciento), B (12,68 por ciento) y AB (2,27 por ciento) respectivamente. Los fenotipos O y B presentaron significación estadística para la ocurrencia de la COVID-19, con valores de p < 0,05. No se encontró significación estadística en cuanto al predominio de un fenotipo particular y la necesidad de cuidados intensivos. Conclusiones: La relación del grupo sanguíneo ABO en la infectividad por SARS-CoV-2 y la gravedad de la enfermedad por la COVID-19 requiere estudios adicionales ya que los actuales no son concluyentes(AU)

Introduction: Different studies have proposed the relationship between the blood groups of ABO system and the susceptibility to COVID-19 and its importance in the course of the disease. Objective: To determine the phenotypic frequency of ABO and RhD blood groups in a group of patients with active SARS-CoV-2 infection. Methods: A descriptive, cross-sectional, case-control study was conducted to determine the ABO and RhD phenotypic frequency in a group of patients with COVID-19 active disease. Nine hundred twenty eight blood samples and 1050 samples belonging to healthy individuals as control group were studied. The ABO and RhD blood group was determined by the tube agglutination method with anti-A, anti-B, anti-A+B, and anti-D blood classifying sera. The results were expressed in absolute and relative frequencies and the association of the blood group with the severity of the disease was determined by the non-parametric χ2 test with a significance level of p ≤ 0.05. Results: A predominance of phenotype O (49.24percent) was observed, followed by A (35.79percent), B (12.68percent) and AB (2.27percent) respectively. The O and B phenotypes showed statistical significance for the occurrence of COVID-19, with p values < 0.05. No statistical significance was found regarding the prevalence of a particular phenotype and the need for intensive care. Conclusions: The relationship of the ABO blood group in the infectivity of SARS-CoV-2 and the severity of the disease by COVID-19 requires additional studies, since the current ones are not conclusive(AU)

Caracterización epidemiológica de pacientes con COVID-19 en la Región Sanitaria de Francisco Morazán, Honduras / Epidemiological characterization of patients with COVID-19 in the Sanitary Region of Francisco Morazán, Honduras

Antecedentes: La infección por el virus SARS- CoV-2 causa la enfermedad por coronavirus 2019 ( COVID-19). Objetivo: Caracterizar epidemiológicamente al paciente con COVID-19, Región Sanitaria Departamental de Francisco Morazán (RSDFM), Honduras, marzo 2020-enero 2021. Métodos: Estudio descriptivo retrospectivo. Incluyó n=11,401 usuarios a quienes se les realizó confirmación diagnóstica en la RSDFM. Se calculó incidencia general y mensual de COVID-19 como tasas por 10,000 habitantes, tasas de incidencia municipal (casos positivos/10,000) y tasa de letalidad (fallecidos/100 casos positivos). Resultados: Del total de 3,680 usuarios, el promedio de edad de los casos positivos fue 36.8 años (DS+/-17.9); sexo femenino 53.3% (1,962), procedencia Valle de Ángeles 20.4% (752). El nexo epidemiológico fue contacto con familiar o amigo positivo o fallecido por COVID-19 en 96.3% (3,544). La tasa general de incidencia fue 92.4/10,000. El municipio de Valle de Ángeles presentó la tasa de incidencia más elevada 366.1/10,000. La tasa de letalidad fue 1.8% (68/3680). Discusión: Los hallazgos de este estudio son compatibles con otros autores con respecto a las características epidemiológicas y sintomatología, identificando mayor riesgo de mortalidad en los individuos con edad ≥60 años (35/418 vs <60 años 32/3194; p=0.000, OR: 8.60, IC95%: 5.15-14.37), así como para el sexo masculino (48/1670 vs 20/1942; p=0.000, OR:2.79, IC95%: 1.61- 4.89). Los meses de mayor incidencia de casos en la RSDFM fueron los meses de junio a julio del 2020 y diciembre del 2020 a enero del 2021. Estudios de este tipo fortalecen el abordaje epidemiológico de las epidemias/pandemias...(AU)

Biallelic TET2 mutations confer sensitivity to 5'-azacitidine in acute myeloid leukemia.

Precision medicine can significantly improve outcomes for patients with cancer, but implementation requires comprehensive characterization of tumor cells to identify therapeutically exploitable vulnerabilities. Here, we describe somatic biallelic TET2 mutations in an elderly patient with acute myeloid leukemia (AML) that was chemoresistant to anthracycline and cytarabine but acutely sensitive to 5'-azacitidine (5'-Aza) hypomethylating monotherapy, resulting in long-term morphological remission. Given the role of TET2 as a regulator of genomic methylation, we hypothesized that mutant TET2 allele dosage affects response to 5'-Aza. Using an isogenic cell model system and an orthotopic mouse xenograft, we demonstrate that biallelic TET2 mutations confer sensitivity to 5'-Aza compared with cells with monoallelic mutations. Our data argue in favor of using hypomethylating agents for chemoresistant disease or as first-line therapy in patients with biallelic TET2-mutated AML and demonstrate the importance of considering mutant allele dosage in the implementation of precision medicine for patients with cancer.

Alteraciones hematológicas en sangre periférica de pacientes con COVID-19 / Molecular study of leukemias: essential tool for the hematologist

Introducción: Los primeros casos con neumonía atípica de etiología desconocida fueron reportados en Wuhan, China en diciembre de 2019. En enero 2020 se describió como agente causal un nuevo tipo de virus de la familia Coronaviridae, denominado SARS-CoV-2. Objetivo: Evaluar la significación clínica de los cambios hematológicos y morfológicos en la sangre periférica de pacientes con COVID-19. Métodos: Se realizó un estudio descriptivo, observacional, transversal que incluyó a los pacientes con COVID-19 que ingresaron en el Hospital Clínico Quirúrgico Docente Freyre de Andrade desde el 1ro de junio hasta 31 de septiembre de 2021. Los pacientes fueron asignados a dos grupos según fueron admitidos, en las unidades de vigilancia intensiva o en la unidad de cuidados intensivos. Se les realizó hemograma completo y lámina periférica el día del ingreso para evaluar la significación clínica de estas variables en la evolución de estos pacientes. Resultados: El sexo femenino predominó en los pacientes ingresados en unidades de vigilancia intensiva (67,36 %) y el masculino en los ingresados en unidades de cuidados intensivos (63,26 %). La media de edad fue mayor en el grupo de pacientes en cuidados intensivos (65,83 años). La leucocitosis y el menor recuento de plaquetas predominaron en los pacientes ingresados en cuidados intensivos, seguido de linfopenia. Las macroplaquetas, las vacuolas citoplasmáticas y las granulaciones tóxicas fueron más frecuentes en el grupo de cuidados intensivos. Conclusiones: El hemograma y el frotis de sangre periférica son útiles para diagnosticar y predecir la evolución de los pacientes y permiten un mejor manejo de la infección.

Introduction: The first cases of atypical pneumonia of unknown etiology were reported in Wuhan, China in December 2019. In January 2020 a new virus from Coronaviridae family was described as causal agent and was named SARS-COV-2. Objectives: To evaluate the clinical significance of numerical values of complete blood count (CBC) and morphologic changes on peripheral blood on patients with COVID-19. Methods: A descriptive, observational, transversal study included patients with diagnosis of COVID-19 admitted in Freyre de Andrade Hospital in Havana, between June 1st and September 31st of 2022 was carried out. Patients were assigned to two groups according to their admission in intensive vigilance ward or intensive care unit. CBC test and peripheral blood smear were performed on admission day to evaluate the significance on clinical evolution. Results: Female sex predominated on intensive vigilance group (67,36 %) and male in intensive care group (63,26 %). Media of age was superior in intensive care group (67,83 years). Leukocytosis and low level of platelets count were significantly more common in more severe group followed by lymphopenia. The presence of big platelets, cytoplasmic vacuoles and toxic granules were more common in intensive care unit group. Conclusions: The CBC and peripheral blood smear are useful tools to diagnose and predict clinical evolution and allow a better management of infection.

Electroforesis de isoenzimas de fosfatasa alcalina: utilidad diagnóstica en pacientes con enfermedad de células falciformes / Alkaline phosphatase isoenzyme electrophoresis: diagnostic utility in patients with sickle cell disease

Introducción: Las fosfatasas alcalinas (FAL) humanas son indicadores enzimáticos de daño de órganos. Las complicaciones de la drepanocitosis incluyen lesión de órganos debido a la reperfusión, la vasculopatía proliferativa y la anemia hemolítica. Objetivo: Demostrar la utilidad de la determinación de la actividad enzimática de la FAL y la movilidad electroforética de las isoenzimas séricas de FAL en pacientes con drepanocitosis en estado basal y durante las crisis. Métodos: Estudio descriptivo, longitudinal, prospectivo en 85 individuos adultos, 25 controles sanos y 60 pacientes, entre enero y diciembre/2018. Variables estudiadas: genotipos (SS/Sβo, SC/Sβ+), edad, sexo, actividad de FAL e isoenzimas por electroforesis en gel de agarosa con y sin lectina: hepática 1 (H1) y (H2); placenta 1(P1), ósea, intestinales 1, 2, 3 (I1.2.3) en estado basal y crisis. Resultados: La actividad de la FAL fue significativamente mayor en los pacientes que en los controles. Hubo diferencias significativas en la actividad de la FAL y de la fracción H1+P1/1 de pacientes en estado basal en relación con el grupo control. La actividad de la enzima y las isoenzimas no mostró diferencias significativas entre los genotipos. Igual comportamiento se observó en la actividad de las enzimas e isoenzimas durante las crisis vasoclusivas dolorosas y hepáticas. Se encontraron diferencias significativas en la actividad de la fracción hepática H1+P1/1 entre los grupos de 20-29 y 40-49 años Conclusiones: La determinación de la FAL en los pacientes con drepanocitosis es útil y permite establecer un perfil isoenzimático personalizado, con importancia pronóstica como un marcador biológico de alarma(AU)

Introduction: Human alkaline phosphatases (ALP) are enzymatic indicators of organ damage. Complications of sickle cell disease include injury to organs due to reperfusion injury, proliferative vascular disease, and hemolytic anemia. Objective: To demonstrate the usefulness of determing ALP activity and the electrophoretic mobility of the serum ALP isoenzymes in patients with sickle cell disease at base line and during the crises. Methods: A descriptive, longitudinal, prospective study was carried out in 85 adult individuals, 25 healthy controls and 60 patients, between January and December/2018. Studied variables: genotypes (SS/SβO, SC/Sβ+), age, sex, ALP activity and isoenzymes by agarose gel electrophoresis with and without lectin: hepatic 1 (H1) and (H2); placenta 1 (P1), bone, intestinal 1, 2, 3 (I1.2.3) in basal state and crisis. Results: ALP activity was significantly higher in patients than in controls. Significant differences were found in the activity of the ALP and fraction H1+P1/1 of patients in basal state in relation to the control group. The activity of the enzyme and the isoenzymes showed no significant differences between genotypes. The same behavior was observed in the activity of enzymes and isoenzymes during painful and liver vasooclusive crises. Significant differences were found in the activity of the liver fraction H1+P1/1 between the groups of 20-29 and 40-49 years. Conclusions: The determination of the ALP in patients with sickle cell disease is useful and allows to establish a personalized isoenzimatic profile, with prognostic importance as a biological alarm marker(AU)

Influencia de la carga alélica del JAK2V617F en pacientes cubanos con trombocitemia esencial y mielofibrosis primaria / Influence of JAK2V617F allelic burden in Cuban patients with essential thrombocythemia and primary myelofibrosis

Introducción: La frecuencia de la mutación JAK2V617F se estima entre el 50 y 60 por ciento en pacientes con trombocitemia esencial y mielofibrosis primaria. El 30 por ciento de los pacientes con policitemia vera y mielofibrosis primaria. Entre 2-4 por ciento de los pacientes con trombocitemia esencial presentan pérdida de heterocigosidad. Objetivos: Evaluar la influencia de la carga alélica de la mutación JAK2V617F y su relación con variables clínico-hematológicas en el diagnóstico de estas enfermedades en pacientes cubanos. Métodos: Se realizó un estudio retrospectivo, descriptivo y longitudinal en el Instituto de Hematología e Inmunología entre 2010 y 2020. Se incluyeron todos los pacientes con sospecha de trombocitemia esencial y mielofibrosis primaria con muestras de ADN válidas. Se les cuantificó la carga alélica de la mutación por PCR en tiempo real. Resultados: Se detectó la mutación en 66,7 por ciento de los diagnosticados con trombocitemia esencial y mielofibrosis primaria. El 62,5 por ciento de los pacientes con mielofibrosis primaria fueron homocigotos a la mutación, mientras que en la trombocitemia esencial solo el 20,8 por ciento. La diferencia de medias de cargas alélicas entre ambas enfermedades fue estadísticamente significativa. No se encontraron diferencias significativas en la comparación de las variables clínicas y hematológicas en estas enfermedades ni asociación con la carga alélica con excepción de las plaquetas en la mielofibrosis primaria. Conclusiones: El estudio estuvo limitado por la escasa muestra de pacientes, pero se corresponde con otras investigaciones que sostienen el concepto de que la presentación fenotípica de las neoplasias mieloproliferativasestá influenciada por la carga mutacional del JAK2V617F(AU)

Introduction: The frequency of the JAK2V617F mutation is estimated to be between 50 percent and 60 percent in patients with essential thrombocythemia and primary myelofibrosis. 30 percent of patients with polycythemia vera and primary myelofibrosis and 2-4 percent of patients with essential thrombocythemia show loss of heterozygosity. Objectives: To evaluate the influence of the allelic load of the JAK2V617F mutation in the diagnosis of these diseases in Cuban patients and its relationship with clinical-hematological variables. Methodology: A retrospective, descriptive and longitudinal study was carried out at the Institute of Hematology and Immunology between 2010 and 2020. All patients with suspected essential thrombocythemia and primary myelofibrosis with valid DNA samples were included. The allelic load of the mutation was quantified by real-time PCR. Results: The mutation was detected in 66.7 percent of those diagnosed with essential thrombocythemia and primary myelofibrosis. 62.5 percent of the patients with primary myelofibrosis were homozygous for the mutation, while in essential thrombocythemia only 20.8 percent. The difference in mean allelic loads between both diseases was statistically significant. No significant differences were found in the comparison of clinical and hematological variables in these diseases or association with allelic load, with the exception of platelets in primary myelofibrosis. Conclusions: The study was limited by the small sample of patients, but it corresponds to other investigations that support the concept that the phenotypic presentation of myeloproliferative neoplasms is influenced by the mutational load of JAK2V617F(AU)

Oncolytic virus-mediated expansion of dual-specific CAR T cells improves efficacy against solid tumors in mice.

Oncolytic viruses (OVs) encoding a variety of transgenes have been evaluated as therapeutic tools to increase the efficacy of chimeric antigen receptor (CAR)-modified T cells in the solid tumor microenvironment (TME). Here, using systemically delivered OVs and CAR T cells in immunocompetent mouse models, we have defined a mechanism by which OVs can potentiate CAR T cell efficacy against solid tumor models of melanoma and glioma. We show that stimulation of the native T cell receptor (TCR) with viral or virally encoded epitopes gives rise to enhanced proliferation, CAR-directed antitumor function, and distinct memory phenotypes. In vivo expansion of dual-specific (DS) CAR T cells was leveraged by in vitro preloading with oncolytic vesicular stomatitis virus (VSV) or reovirus, allowing for a further in vivo expansion and reactivation of T cells by homologous boosting. This treatment led to prolonged survival of mice with subcutaneous melanoma and intracranial glioma tumors. Human CD19 CAR T cells could also be expanded in vitro with TCR reactivity against viral or virally encoded antigens and was associated with greater CAR-directed cytokine production. Our data highlight the utility of combining OV and CAR T cell therapy and show that stimulation of the native TCR can be exploited to enhance CAR T cell activity and efficacy in mice.

Morbilidad y mortalidad de 599 pacientes con drepanocitosis en el Instituto de Hematología e Inmunología / Morbidity and mortality of 599 sickle cell disease patients in the Institute of Hematology and Immunology

Introducción: La drepanocitosis es la anemia hemolítica congénita más común del mundo. Entre el 5 y 15 por ciento de la población mundial es portadora de la hemoglobina S y en Cuba, la frecuencia es de 3,08 por ciento, lo que representa un problema de salud pública. Objetivo: Caracterizar el cuadro clínico, el perfil hematológico y la probabilidad de supervivencia de los pacientes con drepanocitosis en el Instituto de Hematología e Inmunología. Método: Se realizó estudio descriptivo, longitudinal y retrospectivo, que incluyó todos los enfermos seguidos, al menos dos años, en la institución, entre enero de 1973 y diciembre del 2009. Resultados: Se incluyeron 599 pacientes (285 masculinos), 439 SS/Sβ0tal y 160 SC/Sβ+tal. El seguimiento medio fue de 17,6±9,5 años. Predominaron los pacientes entre 20 y 59 años. Los eventos clínicos más frecuentes fueron las crisis vasoclusivas dolorosas, las infecciones, el síndrome torácico agudo y las complicaciones hepáticas. Los valores de reticulocitos, plaquetas, leucocitos y hemoglobina fetal fueron significativamente mayores en los pacientes SS/Sβ0tal; no así la hemoglobina total que fue mayor en los SC/Sβ+tal. La probabilidad de supervivencia global de los pacientes a los 45 años fue de 69 por ciento. Los accidentes vasculares encefálicos (17,5 por ciento), las complicaciones hepáticas (17,5 por ciento) y las cardíacas (14,28 por ciento) fueron las principales causas de muerte. Conclusiones: La distribución demográfica y por hemoglobinopatías, el cuadro clínico, y el perfil hematológico fueron similares a los encontrados en pacientes de otras regiones geográficas, excepto la frecuencia de complicaciones hepáticas que fue mayor. La probabilidad de supervivencia fue similar con los mejores centros de atención en el mundo(AU)

Introduction: Sickle cell disease is the most common congenital hemolytic anemia in the world. Between 5 to 15 percent of the world population is a carrier of hemoglobin S and in Cuba, the frequency is 3.08 percent, which represents a public health problem. Objective: To characterize the clinical picture, the hematological profile, and the probability of survival of patients with sickle cell disease at the Institute of Hematology and Immunology. Method: A descriptive, longitudinal and retrospective study was carried out, which included all patients followed up for at least two years at the institution between January 1973 and December 2009. Results: 599 patients (285 male), 439 SS/Sβ0tal and 160 SC/Sβ+tal, were included. The mean follow-up was 17.6±9.5 years. Patients between 20 and 59 years old predominated. The most frequent clinical events were painful vasocclusive crises, infections, acute chest syndrome, and liver complications. The reticulocytes, platelets, leukocytes and fetal hemoglobin values ​​were significantly higher in the SS/Sβ0tal patients, but not the total hemoglobin, which was higher in the SC/Sβ+tal. The overall survival probability of patients at 45 years was 70 percent. Stroke (17.5 percent), liver complications (17.5 percent), and cardiac complications (14.28 percent) were the main causes of death. Conclusions: The demographic distribution and by hemoglobinopathies, the clinical events, and the hematological profile were similar to those found in patients from other geographic regions, except the frequency of liver complications, which was higher. The probability of survival was comparable with the best care centers in the world(AU)

Persistently positive PCR SARS-CoV-2 at low cycle threshold in an immunosuppressed patient

ABSTRACT We describe the very prolonged course of the disease in an immunosuppressed patient with persistently positive PCR against SARS-CoV-2 with low cycle threshold for at least 114 days.

Estudio del desempeño de dos métodos de detección de antígenos rápidos en hisopados combinados y en hisopados nasofaríngeos para la detección de SARS-CoV-2 / Performance study of two rapid antigen detection methods in combined swabs and nasopharyngeal swabs for detection of SARS-CoV-2

Resumen Se realizó una comparación del desempeño de los métodos rápidos de detección de antígenos para el diagnóstico de SARS-CoV-2 Veritor System de Becton Dickinson y Panbio de Abbott versus una reacción en cadena de la polimerasa con retrotranscripción en tiempo real (RT-PCR) de Roche en un triage de demanda espontánea de pacientes febriles de un hospital público, para la detección de COVID-19. Se procesaron 36 hisopados de pacientes sospechosos por los tres métodos. La concordancia entre ambos métodos con la RT-PCR fue del 97%. La sensibilidad de los métodos de detección de antígenos versus la RT-PCR fue del 83% y la especificidad fue del 100%. El valor predictivo positivo (VPP) fue del 100% y el valor predictivo negativo (VPN) fue del 97%. La muestra que resultó discordante presentó un ciclo umbral (Ct) de 29,8. El método para detección de antígenos tuvo un desempeño aceptable, incluso con resultados de sensibilidad mayores que los declarados por los fabricantes (84% para el Veritor System y 93,3% para el Panbio).

Abstract A comparison of the performance of the rapid antigen detection methods for the diagnosis of SARS-CoV-2 Veritor System from Becton Dickinson and Panbio from Abbott versus a real-time polymerase chain reaction with reverse transcription (RT-PCR) Roche in a spontaneous demand triage of febrile patients of a public hospital was made, for the detection of COVID-19. Thirty six swabs from suspected patients were processed by the three methods. The concordance between both methods with RT-PCR real time was 97%. The sensitivity of the antigen detection methods versus RT-PCR real time was 83% and specificity was 100%. The positive predictive value (PPV) was 100% and the negative predictive value (NPV) was 97%. The sample that was discordant presented a threshold point (Ct) of 29.8. The method for antigen detection resulted in an acceptable performance, even with S results higher than those declared by the manufacturers (84% for the Veritor System and 93.3% for the Panbio).

Resumo Uma comparação do desempenho dos métodos rápidos de detecção de antígenos para o diagnóstico deSARS-CoV-2 Veritor System de Becton Dickinson e Panbio de Abbott versus uma reação em cadeia da polimerasecom transcrição reversa em tempo real (RT-PCR) da Roche em uma triagem de demanda espontâneade pacientes febris de um hospital público, para a detecção de COVID-19. Foram processadas 36 amostrasde esfregaços de pacientes suspeitos pelos três métodos e a concordância entre os dois métodos com aRT-PCR foi de 97%. A sensibilidade dos métodos de detecção de antigenos versus a RT-PCR foi de 83% ea especificidade de 100%. O valor preditivo positivo (VPP) foi de 100% e o valor preditivo negativo (VPN)foi de 97%. A amostra que resultou discordante apresentou um ciclo limiar (Ct) de 29,8. O método paradetecção de antígenos teve um desempenho aceitável, mesmo com resultados de sensibilidade superioresaos declarados pelos fabricantes (84% para o Veritor System e 93,3% para o Panbio).

Emicizumab in pediatric hemophilia: Bleeding and surgical outcomes from a single-center retrospective study.

Real-world data describing emicizumab prophylaxis in pediatric hemophilia A is limited with current literature providing a heterogenous approach to procedural management. We performed a retrospective review on the 28 patients who have been treated with emicizumab prophylaxis at Texas Children's Hospital from 2018 to 2021. After starting emicizumab, the mean annualized bleeding rate reduced from 3.61 to 0.44. Seven surgical procedures were performed in the cohort, and all treated with pre- and postoperative factor replacement resulting in one minor bleeding event. We demonstrate a successful experience with emicizumab prophylaxis and safe perioperative approach with a focus on minimizing postoperative bleeding.

Dinámica ambiental en la Eco-región Lachuá: una representación espacial desde la perspectiva de los guardarecursos / Environmental dynamics in Lachuá Ecoregión: a spatial representation from park rangers perspective

El mapeo participativo es una modalidad de interacción horizontal entre los actores implicados en procesos de toma de decisiones, que tiene como finalidad la representación gráfica del territorio. Para ello, se combina la percepción local con herramientas modernas de cartografía. Con la finalidad de documentar la percepción espacial de los guardarecursos del Parque Nacional Laguna Lachuá (PNLL) con relación a la dinámica de la biodiversidad actual en la Eco-región Lachuá, se utilizó la herramienta del mapa hablado durante un taller con los 11 guardarecursos del parque en 2018. Los mapas de la Eco-región se dividieron en cuatro zonas: Noreste (NE), Sureste (SE), Suroeste (SO) y Noroeste (NO), dentro del PNLL como en la zona de amortiguamiento. Se contabilizaron los elementos favorables y desfavorables para la biodiversidad reportadas para cada zona. Se comparó la información proporcionada por los guardarecursos con las imágenes satelitales de la Eco-región mediante un análisis de Sistemas de Información Geográfica (SIG). De esta manera, se brinda un enfoque integral para comprender los patrones del paisaje actual, ya que estos son resultado de procesos socio-económicos y políticos que culminaron en conflictos del manejo de la tierra y los recursos. Se identificó que en el PNLL los elementos desfavorables más reportados fueron los cultivos, carreteras y asentamientos humanos. En la zona de amortiguamiento los elementos desfavorables corresponden a los cultivos, (p.ej.: palma africana) y los asentamientos humanos. Además, las áreas con mayor cobertura boscosa son las zonas NE y NO en el PNLL.

Participatory mapping facilitates horizontal interaction among interested parties in decision-making processes, which pursues the graphic representation of the territory. This technique unifies local perception with modern cartography. It eases communication and has been used to document spatial representations and resource management thus, integrating tools such as a Geographic Information System (GIS) might facilitate solutions in land conflicts and community governance. In this article, we share the findings regarding the spatial perception biodiversity dynamics of park rangers in National Park Laguna Lachuá (PNLL) during a workshop in 2018, documented through the "talking maps" tool. To analyze each map, we used GIS sofware, by dividing the PNLL and its buffer zone into four quadrants: Northeast (NE), Southeast (SE), Southwest (SO), and Northwest (NO). We registered every record reported by the park rangers from a list of positive and negative elements that have an effect on biodiversity. We then compared the information reported with spatial layers in GIS to evaluate which elements were detectable and viceversa. This is relevant since participatory mapping allows a more integral understanding of landscape patterns than GIS on its own and given the fact that the actual landscape is the result of several socio-economic and political processes that have created land and resource management conflicts. We identified that the unfavorable elements inside the PNLL are agriculture, roads, and human settlements, and in the buffer zone were agriculture, African palm, and human settlements. The quadrants with more forest cover corresponded to NE and NO inside the park.

Role of anticoagulation in the management of tumor thrombus: A 10-year single-center experience.

BACKGROUND: Children with cancer diagnosis are overall at a higher risk of thrombosis. For a newly diagnosed blood clot, patients are commonly started on anticoagulants to prevent further extension and embolization of the clot. In the rare instance that a pediatric patient has a tumor thrombus, role of anticoagulation is less clear. PROCEDURE/METHODS: Patients under 21 years of age with a finding of tumor thrombus on imaging from 2010 to 2020 at Texas Children's Hospital were identified and their medical records were reviewed. RESULTS: A total of 50 patients were identified. Most thrombi were incidental findings at diagnosis; however, two patients presented with pulmonary embolism (PE). Inferior vena cava extension was noted in 36% of the patients, and 24% patients had an intracardiac tumor thrombus. Anticoagulation was initiated in 10 patients (20%). There was no difference in the rate of bland thrombus formation and/or embolization in patients who did or did not receive anticoagulation. However, three of the six patients with asymptomatic tumor thrombus who were started on anticoagulation had bleeding complications compared to only two patients in the no anticoagulation cohort (p < .05). CONCLUSION: Children with intravascular extension of solid tumors were not commonly started on anticoagulation at the time of diagnosis, irrespective of the extent of tumor thrombus. Furthermore, we observed a significant trend toward higher incidence of bleeding complications after initiation of anticoagulation for asymptomatic tumor thrombus. There is inadequate evidence at this time to support routine initiation of anticoagulation in pediatric patients with intravascular extension of solid tumors.

Rate of thrombosis in children and adolescents hospitalized with COVID-19 or MIS-C.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with thrombotic complications in adults, but the incidence of COVID-19-related thrombosis in children and adolescents is unclear. Most children with acute COVID-19 have mild disease, but coagulopathy has been associated with multisystem inflammatory syndrome in children (MIS-C), a postinfectious complication. We conducted a multicenter retrospective cohort study to determine the incidence of thrombosis in children hospitalized with COVID-19 or MIS-C and evaluate associated risk factors. We classified patients into 1 of 3 groups for analysis: COVID-19, MIS-C, or asymptomatic SARS-CoV-2. Among a total of 853 admissions (COVID-19, n = 426; MIS-C, n = 138; and asymptomatic SARS-CoV-2, n = 289) in 814 patients, there were 20 patients with thrombotic events (TEs; including 1 stroke). Patients with MIS-C had the highest incidence (9 [6.5%] of 138) vs COVID-19 (9 [2.1%] of 426) or asymptomatic SARS-CoV-2 (2 [0.7%] of 289). In patients with COVID-19 or MIS-C, a majority of TEs (89%) occurred in patients age ≥12 years. Patients age ≥12 years with MIS-C had the highest rate of thrombosis at 19% (9 of 48). Notably, 71% of TEs that were not present on admission occurred despite thromboprophylaxis. Multivariable analysis identified the following as significantly associated with thrombosis: age ≥12 years, cancer, presence of a central venous catheter, and MIS-C. In patients with COVID-19 or MIS-C, hospital mortality was 2.3% (13 of 564), but it was 28% (5 of 18) in patients with TEs. Our findings may help inform pediatric thromboprophylaxis strategies.

Effective hemostasis in children with Von Willebrand factor defects undergoing adenotonsillar procedures.

INTRODUCTION: Children with low von Willebrand factor (VWF) activity or type 1 von Willebrand disease (VWD) have increased risk of bleeding after adenotonsillar procedures and the optimal perioperative management to minimize bleeding is unknown. AIM: To report the effectiveness and safety of an institutional protocol in minimizing postoperative bleeding in children with type 1 VWD or low VWF activity. METHODS: We conducted a retrospective chart review in children with type 1 VWD or low VWF activity treated via an institutional protocol that utilizes repeated doses of Desmopressin acetate (DDAVP, 1-deamino 8-D arginine- vasopressin) or VWF concentrate, brief hospitalization for observation and extended use of oral epsilon aminocaproic acid (EACA). RESULTS: From 2010 to 2017, 13 children underwent an adenotonsillar procedure and were treated with this protocol. Although 7.6% had minor immediate bleeding and 23% had minor delayed bleeding, no patients experienced major bleeding or required transfusion, additional surgery or other measures not specified by the protocol. Mild hyponatremia was observed in 80% of patients who received DDAVP. CONCLUSION: Our institutional protocol specifying repeated dosing of DDAVP or VWF concentrate to sustain elevated VWF levels during periods of highest bleeding risk and extended use of EACA is effective at preventing major bleeding episodes after adenotonsillar procedures. However, this analysis raised safety concerns that prompted changes in the institutional protocol and highlight the need for further prospective studies to determine the optimal strategy for safely reducing bleeding complications in these patients.

Exohidrolasas fructosílicas y su importancia en el metabolismo de fructanos en Agave tequilana Weber var. azul / Fructan exohydrolases y its importance in the metabolism of fructans in Agave tequilana Weber var. azul / Exoidrolases de frutanos e sua importância no metabolismo de frutanos em Agave tequilana Weber var. azul

Resumen Los fructanos son carbohidratos de estructura química diversa distribuidos en diferentes taxa. En las plantas, además de constituir una importante fuente de carbono, han sido asociados con la tolerancia a diferentes tipos de estrés. La biosíntesis de estos compuestos se lleva a cabo por la acción de las enzimas fructosiltransferasas, mientras que su degradación es mediada por las exohidrolasas fructosílicas, ambos tipos forman parte de la familia 32 de las enzimas hidrolasas glicosídicas. Las exohidrolasas fructosílicas son exoenzimas que liberan secuencialmente residuos de fructosa terminales de los fructanos para hacerlos disponibles como fuente de carbono en diferentes procesos celulares o bien moléculas de señalización. En esta revisión se hace una descripción de los fructanos y las exohidrolasas fructosílicas en algunas plantas importantes para el consumo humano y para el aprovechamiento industrial, con un enfoque particular en el género Agave, específicamente en A. tequilana. Concluimos, que el estudio de las exohidrolasas fructosílicas en agaves podría ser útil en varias aplicaciones biotecnológicas como en la hidrólisis de estructuras de fructanos no digeridos durante la etapa de cocción del agave en el proceso de producción de tequila. Sin embargo, el primer paso es conocer la funcionalidad de estas enzimas, lo que podría facilitar su incorporación en diferentes procesos biotecnológicos.

Abstract Fructans are carbohydrates of diverse chemical structure that are distributed in different taxa. In plants, in addition to be an important source of carbon, they have been associated with tolerance to different types of stress. The biosynthesis of these compounds is carried out by the action of enzymes called fructosyltransferases, while their degradation is mediated by fructan exohydrolases, both types are part of the 32 family of glycosidic hydrolase enzymes. Fructan exohydrolases are exo-enzymes that sequentially release terminal fructose residues from fructans to make them available as carbon sources for different cellular processes or as signaling molecules. In this review, a description is made of fructans, y of fructosyl exohydrolases in some plants important for human consumption or for industrial use, such as the Agave genus, specifically in A. tequilana. We conclude that the study of fructan exohydrolases in agaves could be useful in various biotechnological applications, for example, in the hydrolysis of undigested fructan structures during the agave cooking stage in the tequila production process. However, the first step is to determinate the enzymatic activity in which they are involved, for its posterior inclusion in biotechnology processes.

Resumo Os frutanos são carboidratos de estrutura química diversificada distribuídos em diferentes táxons. Nas plantas, além de serem uma importante fonte de carbono, eles têm sido associados à tolerância a diferentes tipos de estresse. A biossíntese desses compostos é realizada pela ação das enzimas fructosiltransferases, enquanto sua degradação é mediada por frutossil exohidrolases, ambos os tipos fazem parte da família 32 de enzimas glicosídicas da hidrolase. As exo-hidrolases de frutossil são exo-enzimas que liberam seqüencialmente resíduos terminais de frutose dos frutanos para torná-los disponíveis como fonte de carbono em diferentes processos celulares, ou como sinalizadores. Nesta revisão, é feita uma descrição dos frutanos e das frutossil exohidrolases em algumas plantas importantes para o consumo humano ou para uso industrial, como o gênero Agave, especificamente no A. tequilana. Concluímos que o estudo de frutossil exo-hidrolases em agaves pode ser útil em várias aplicações biotecnológicas, por exemplo, na hidrólise de estruturas de frutano não digeridas durante a fase de cozimento da agave no processo de produção de tequila. Para isso, o primeiro passo é conhecer o tipo de atividade enzimática que eles desempenham, para sua posterior inclusão no campo da biotecnologia.