Continuous prolonged prone positioning in COVID-19-related ARDS: a multicenter cohort study from Chile.

BACKGROUND: Prone positioning is currently applied in time-limited daily sessions up to 24 h which determines that most patients require several sessions. Although longer prone sessions have been reported, there is scarce evidence about the feasibility and safety of such approach. We analyzed feasibility and safety of a continuous prolonged prone positioning strategy implemented nationwide, in a large cohort of COVID-19 patients in Chile. METHODS: Retrospective cohort study of mechanically ventilated COVID-19 patients with moderate-to-severe acute respiratory distress syndrome (ARDS), conducted in 15 Intensive Care Units, which adhered to a national protocol of continuous prone sessions ≥ 48 h and until PaO2:FiO2 increased above 200 mm Hg. The number and extension of prone sessions were registered, along with relevant physiologic data and adverse events related to prone positioning. The cohort was stratified according to the first prone session duration: Group A, 2-3 days; Group B, 4-5 days; and Group C, > 5 days. Multivariable regression analyses were performed to assess whether the duration of prone sessions could impact safety. RESULTS: We included 417 patients who required a first prone session of 4 (3-5) days, of whom 318 (76.3%) received only one session. During the first prone session the main adverse event was grade 1-2 pressure sores in 97 (23.9%) patients; severe adverse events were infrequent with 17 non-scheduled extubations (4.2%). 90-day mortality was 36.2%. Ninety-eight patients (24%) were classified as group C; they exhibited a more severe ARDS at baseline, as reflected by lower PaO2:FiO2 ratio and higher ventilatory ratio, and had a higher rate of pressure sores (44%) and higher 90-day mortality (48%). However, after adjustment for severity and several relevant confounders, prone session duration was not associated with mortality or pressure sores. CONCLUSIONS: Nationwide implementation of a continuous prolonged prone positioning strategy for COVID-19 ARDS patients was feasible. Minor pressure sores were frequent but within the ranges previously described, while severe adverse events were infrequent. The duration of prone session did not have an adverse effect on safety.

Rhopalosiphum padi (Hemiptera: Aphididae) responses to volatile cues from Barley yellow dwarf virus-infected wheat.

In choice bioassays, Rhopalosiphum padi L. nonviruliferous apterae preferentially locate near volatile organic compounds (VOCs) emitted from Barley yellow dwarf virus (BYDV)-infected wheat plants compared with VOCs from noninfected plants. However, the specific VOCs responsible for R. padi responses are unknown. It is unclear also if R. padi responses to BYDV-infected wheat are caused by arrestment or attraction. Additionally, the responses of viruliferous apterae and nonviruliferous alate to BYDV-infected wheat have not been examined. R. padi responses were studied through emigration, immigration, and settling laboratory bioassays using BYDV-infected and noninfected wheat plants. Two wheat genotypes, virus-susceptible Lambert and virus-resistant Lambert-derived transgenic 103.1J expressing the BYDV-PAV coat protein gene, were evaluated. In a settling bioassay, alates preferentially settled on noninfected 103.1J. Responses of viruliferous and nonviruliferous R. padi to virus-infected, noninfected, and sham-inoculated (exposed to nonviruliferous aphids) Lambert and 103.1J were examined in separate bioassays. A paper leaf model served as a control. Immigration by viruliferous apterae was significantly lower toward the paper leaf model, but no significant differences were observed among plant treatments. Nonviruliferous apterae exhibited no significant differences in emigration among treatments, suggesting no arrestment occurred. Nonviruliferous apterae significantly preferred to immigrate toward BYDV-infected Lambert. Immigration toward the paper leaf model was significantly lower compared with plant treatments. Responses of R. padi to VOCs were tested by applying compounds to paper leaf models at concentrations designed to mimic those present in headspace of wheat plants. Nonviruliferous apterae immigrated in significantly greater numbers toward paper leaf models individually treated with nonanal, (Z)-3-hexenyl acetate, decanal, caryophyllene, and undecane than toward paper leaf models that served as controls and toward leaf models treated with synthetic blends made to mimic headspace of BYDV-infected compared with blends made to mimic headspace of noninfected wheat plants. Results suggest responses of R. padi to BYDV-infected plants are caused by attraction rather than arrestment.

Introduction of imatinib as first-line therapy for chronic myeloid leukemia in Cuba.

INTRODUCTION: Chronic myeloid leukemia is the first malignant disease to be associated with a genetic lesion and is the first leukemia to provide a genotype model conducive to targeted molecular therapy. It is a chronic clonal myeloproliferative disorder, originating in a pluripotent stem cell common to all three hematopoietic lineages, characterized by overproduction of myeloid cells in all stages of maturation. Approval of the use of imatinib in the United States in 2001 and its introduction in the treatment of chronic myeloid leukemia changed the evolution and prognosis of the disease and began the era of molecular therapy for malignancies. Imatinib is highly effective and causes fewer adverse reactions than earlier treatments based on interferon and hydroxyurea. In Cuba, chronic myeloid leukemia has been treated with interferon since 1998. Starting in 2003, imatinib was gradually introduced for use in newly-diagnosed chronic myeloid leukemia patients. OBJECTIVE: Evaluate the use of imatinib as first-line therapy for chronic myeloid leukemia in a group of Cuban patients, based on hematologic, cytogenetic, and molecular response; overall and event-free survival rates; and most frequency and severity of adverse reactions. METHODS: During May 2003 to May 2008, 33 newly-diagnosed chronic myeloid leukemia patients (25 adults, 8 children; <6 months from diagnosis) received a single daily oral dose of imatinib 400 mg from the time of study enrollment. Variables used: (1) to evaluate treatment efficacy: hematologic, cytogenetic, and molecular response; overall and event-free survival; and (2) to evaluate safety: presence of adverse reactions leading to definitive interruption of treatment or death. RESULTS: Complete hematologic response occurred in 100% of patients, major cytogenetic response in 90.9%, and complete cytogenetic response in 48.5%. Molecular response occurred in 36.4% of patients. With a mean follow-up of 39 months, overall survival was 96% and estimated five-year event-free survival was 85%. No adverse reactions occurred in 39.5% of patients. Adverse reactions most frequently observed were myelosuppression (24.2%) and digestive disorders (21.2%). These were followed, in decreasing order, by edema, primarily orbital (9.1%), skin depigmentation (3%), and cardiac arrhythmias (3%). CONCLUSIONS: In the present study, imatinib was effective first-line therapy for patients with newly-diagnosed chronic myeloid leukemia, as determined by overall and event-free survival rates. No severe adverse reactions were observed.

Gen de fusión AML-1/ETO y mutación NPM-1A en leucemia mieloide crónica en crisis blástica mieloide / AML-1/ETO fusion gene and mutation NPM-1A in myeloid chronic leukemia in myeloid blast crisis

La leucemia mieloide crónica es una neoplasia mieloproliferativa de naturaleza clonal que generalmente y de manera progresiva transita por tres fases: crónica, acelerada y crisis blástica. Alrededor del 80 por ciento de los enfermos con leucemia mieloide crónica son diagnosticados durante la fase crónica, 10 por ciento en fase acelerada y otro 10 por ciento durante la crisis blástica. A la presencia del cromosoma Filadelfia y la formación del gen de fusión BCR/ABL, que se traduce en la proteína quimérica pBCR/ABL, le sigue una gran inestabilidad genómica y la adquisición de alteraciones cromosómicas y moleculares adicionales. Algunas alteraciones moleculares, que suelen estar presentes en otras hemopatías malignas, pueden ser adquiridas durante la progresión de la leucemia mieloide crónica a crisis blástica. Se presenta el caso de un paciente que debutó con una leucemia mieloide crónica en crisis blástica, con positividad del gen de fusión BCR/ABL, el gen de fusión AML-1/ETO y la mutación NPM-1A(AU)

Chronic myeloid leukemia is a clonal myeloproliferative neoplasm which generally and progressively goes through three phases: chronic, accelerated and blast crisis. About 80 percent of patients with chronic myeloid leukemia are diagnosed in chronic phase, 10 percent in accelerated phase and 10 percent in blast crisis. The presence of Philadelphia chromosome and the formation of BCR/ABL fusion gene, resulting in the chimeric protein pBCR/ABL, generates a large genomic instability and the acquisition of additional chromosomal and molecular alterations. Some molecular alterations, which are usually present in other hematological malignancies, could be acquired during the progression of chronic myeloid leukemia to blast crisis. This report presents the case of a patient with de novo chronic myeloid leukemia in blast crisis, with positivity of BCR/ABL fusion gene, AML-1/ETO fusion gene and mutation NPM-1A(AU)

Gen de fusión AML-1/ETO y mutación NPM-1A en leucemia mieloide crónica en crisis blástica mieloide / AML-1/ETO fusion gene and mutation NPM-1A in myeloid chronic leukemia in myeloid blast crisis

La leucemia mieloide crónica es una neoplasia mieloproliferativa de naturaleza clonal que generalmente y de manera progresiva transita por tres fases: crónica, acelerada y crisis blástica. Alrededor del 80 por ciento de los enfermos con leucemia mieloide crónica son diagnosticados durante la fase crónica, 10 por ciento en fase acelerada y otro 10 por ciento durante la crisis blástica. A la presencia del cromosoma Filadelfia y la formación del gen de fusión BCR/ABL, que se traduce en la proteína quimérica pBCR/ABL, le sigue una gran inestabilidad genómica y la adquisición de alteraciones cromosómicas y moleculares adicionales. Algunas alteraciones moleculares, que suelen estar presentes en otras hemopatías malignas, pueden ser adquiridas durante la progresión de la leucemia mieloide crónica a crisis blástica. Se presenta el caso de un paciente que debutó con una leucemia mieloide crónica en crisis blástica, con positividad del gen de fusión BCR/ABL, el gen de fusión AML-1/ETO y la mutación NPM-1A(AU)

Chronic myeloid leukemia is a clonal myeloproliferative neoplasm which generally and progressively goes through three phases: chronic, accelerated and blast crisis. About 80 percent of patients with chronic myeloid leukemia are diagnosed in chronic phase, 10 % in accelerated phase and 10 percent in blast crisis. The presence of Philadelphia chromosome and the formation of BCR/ABL fusion gene, resulting in the chimeric protein pBCR/ABL, generates a large genomic instability and the acquisition of additional chromosomal and molecular alterations. Some molecular alterations, which are usually present in other hematological malignancies, could be acquired during the progression of chronic myeloid leukemia to blast crisis. This report presents the case of a patient with de novo chronic myeloid leukemia in blast crisis, with positivity of BCR/ABL fusion gene, AML-1/ETO fusion gene and mutation NPM-1A(AU)

Repulsion by Slit and Roundabout prevents Shotgun/E-cadherin-mediated cell adhesion during Drosophila heart tube lumen formation.

During Drosophila melanogaster heart development, a lumen forms between apical surfaces of contralateral cardioblasts (CBs). We show that Slit and its receptor Roundabout (Robo) are required at CB apical domains for lumen formation. Mislocalization of Slit outside the apical domain causes ectopic lumen formation and the mislocalization of cell junction proteins, E-cadherin (E-Cad) and Enabled, without disrupting overall CB cell polarity. Ectopic lumen formation is suppressed in robo mutants, which indicates robo's requirement for this process. Genetic evidence suggests that Robo and Shotgun (Shg)/E-Cad function together in modulating CB adhesion. robo and shg/E-Cad transheterozygotes have lumen defects. In robo loss-of-function or shg/E-Cad gain-of-function embryos, lumen formation is blocked because of inappropriate CB adhesion and an accumulation of E-Cad at the apical membrane. In contrast, shg/E-Cad loss-of-function or robo gain-of-function blocks lumen formation due to a loss of CB adhesion. Our data show that Slit and Robo pathways function in lumen formation as a repulsive signal to antagonize E-Cad-mediated cell adhesion.

Cuestionario para evaluar la calidad de vida relacionada con la salud de adultos con drepanocitosis / Questionnaire to assess health-related quality of life in sickle cell adults

Los estudios sobre calidad de vida relacionada con salud (CVRS) en drepanocitosis son escasos y no existen instrumentos específicos en español para su evaluación. En este artículo se describe el desarrollo y validación del breve cuestionario específico sobre calidad de vida en drepanocitosis (CEB-S) que ha sido creado para evaluar la calidad de vida de pacientes con drepanocitosis a partir de la valoración que estos hacen de cuánto la enfermedad afecta la calidad de sus vidas. El desarrollo de este instrumento incluyó las fases: creación de preguntas, estudio piloto y estudio de campo. La versión preliminar estuvo formada por 33 preguntas cerradas tipo Likert que se aplicó a 20 hombres y 20 mujeres con drepanocitosis. De su análisis se obtuvo una segunda versión de 30 preguntas en 4 escalas que se aplicó a 104 pacientes. El análisis psicométrico incluyó: evaluación de confiabilidad, validez, sensibilidad, especificidad y eficiencia. Se determinó la confiabilidad del cuestionario en términos de consistencia interna por el índice de Crombach (área física 0,82; área social 0,82; área emocional 0,76; dolor 0,85 y total 0,92). En 69 enfermos se obtuvo un fuerte criterio de validez convergente con el cuestionario de salud SF-36. Se demostró la validez discriminante del CEB-S, al comparar los resultados obtenidos por los pacientes con cualquier tipo de síntoma relacionado con la enfermedad, con los alcanzados por los asintomáticos y también con la estratificación de los enfermos según la gravedad de la anemia en el momento de su aplicación. Esta versión fue considerada como la definitiva

Studies related to quality of life (HRQOL) in sickle cell disease are scarce and there are no specific tools for assessment in Spanish. This article described the development and validation of a brief specific questionnaire on quality of life in sickle cell disease (CEB-S), which has been created to assess the quality of life in patients with sickle cell disease on the basis of their own assessment on how this disease affects their quality of life. The development of this instrument included stages: creation of questions, pilot study and field study. The draft consisted of 33 Likert-type closed questions applied to 20 men and 20 women with sickle cell disease. After an analysis, a second 4-scale thirty question version was accomplished and then applied to 104 patients. Psychometric analysis included: evaluation of reliability, validity, sensitivity, specificity, and efficiency. The reliability of this questionnaire in terms of internal consistency by Cronbach index (physical area 0.82; social area 0.82; emotional area 0.76; pain 0.85 and total 0.92) was determined. Sixty nine patients yielded strong validity criterion consistent with the SF-36 health questionnaire. CEB-S discriminant validity was demonstrated, by comparing the results obtained in patients with any symptoms related to this disease, with those obtained in asymptomatic patients and with the stratification of patients according to the severity of anemia at the time of application. This version was considered final

Cuestionario para evaluar la calidad de vida relacionada con la salud de adultos con drepanocitosis / Questionnaire to assess health-related quality of life in sickle cell adults

Los estudios sobre calidad de vida relacionada con salud (CVRS) en drepanocitosis son escasos y no existen instrumentos específicos en español para su evaluación. En este artículo se describe el desarrollo y validación del breve cuestionario específico sobre calidad de vida en drepanocitosis (CEB-S) que ha sido creado para evaluar la calidad de vida de pacientes con drepanocitosis a partir de la valoración que estos hacen de cuánto la enfermedad afecta la calidad de sus vidas. El desarrollo de este instrumento incluyó las fases: creación de preguntas, estudio piloto y estudio de campo. La versión preliminar estuvo formada por 33 preguntas cerradas tipo Likert que se aplicó a 20 hombres y 20 mujeres con drepanocitosis. De su análisis se obtuvo una segunda versión de 30 preguntas en 4 escalas que se aplicó a 104 pacientes. El análisis psicométrico incluyó: evaluación de confiabilidad, validez, sensibilidad, especificidad y eficiencia. Se determinó la confiabilidad del cuestionario en términos de consistencia interna por el índice de Crombach (área física 0,82; área social 0,82; área emocional 0,76; dolor 0,85 y total 0,92). En 69 enfermos se obtuvo un fuerte criterio de validez convergente con el cuestionario de salud SF-36. Se demostró la validez discriminante del CEB-S, al comparar los resultados obtenidos por los pacientes con cualquier tipo de síntoma relacionado con la enfermedad, con los alcanzados por los asintomáticos y también con la estratificación de los enfermos según la gravedad de la anemia en el momento de su aplicación. Esta versión fue considerada como la definitiva(AU)

Studies related to quality of life (HRQOL) in sickle cell disease are scarce and there are no specific tools for assessment in Spanish. This article described the development and validation of a brief specific questionnaire on quality of life in sickle cell disease (CEB-S), which has been created to assess the quality of life in patients with sickle cell disease on the basis of their own assessment on how this disease affects their quality of life. The development of this instrument included stages: creation of questions, pilot study and field study. The draft consisted of 33 Likert-type closed questions applied to 20 men and 20 women with sickle cell disease. After an analysis, a second 4-scale thirty question version was accomplished and then applied to 104 patients. Psychometric analysis included: evaluation of reliability, validity, sensitivity, specificity, and efficiency. The reliability of this questionnaire in terms of internal consistency by Cronbach index (physical area 0.82; social area 0.82; emotional area 0.76; pain 0.85 and total 0.92) was determined. Sixty nine patients yielded strong validity criterion consistent with the SF-36 health questionnaire. CEB-S discriminant validity was demonstrated, by comparing the results obtained in patients with any symptoms related to this disease, with those obtained in asymptomatic patients and with the stratification of patients according to the severity of anemia at the time of application. This version was considered final(AU)

Anemia drepanocítica y enfermedad de Castleman / Sickle cell anemia and Castleman disease

La enfermedad de Castleman es un proceso linfoproliferativo poco frecuente que se caracteriza por hiperplasia benigna de los ganglios linfáticos. Existen 2 variedades histológicas bien diferenciadas: la hialino-vascular y la plasmo-celular, que a su vez, pueden ser localizadas o multicéntricas. La forma hialino-vascular suele ser asintomática y localizada con mayor frecuencia en mediastino, mientras que la plasmo-celular se presenta frecuentemente con sintomatología sistémica y suele ser difusa o multicéntrica. Por lo poco frecuente de la asociación, presentamos un caso con antecedentes de anemia drepanocítica que después de 12 años de diagnóstico de una enfermedad de Castleman localizada, variante de células plasmáticas y exéresis total, hizo una recaída ganglionar con la misma variante, con buena respuesta clínica al tratamiento(AU)

Castleman's disease is a rare lymphoproliferative process characterized by benign hyperplasia of the lymph nodes. There are 2 distinct histologic variants: hyaline-vascular and cellular plasmodia, which in turn, may be localized or multicentric. The hyaline vascular form is usually asymptomatic and most often located in the mediastinum, whereas cellular plasmodia frequently presents with systemic symptoms and it is usually diffuse or multicentric. Due to the rarity of this association, we present a case with a history of sickle cell disease 12 years after diagnosis of localized Castleman's disease, plasma cell variant and total excision, lymph node had a relapse with the same variant, having good clinical treatment response(AU)

Anemia drepanocítica y enfermedad de Castleman / Sickle cell anemia and Castleman disease

La enfermedad de Castleman es un proceso linfoproliferativo poco frecuente que se caracteriza por hiperplasia benigna de los ganglios linfáticos. Existen 2 variedades histológicas bien diferenciadas: la hialino-vascular y la plasmo-celular, que a su vez, pueden ser localizadas o multicéntricas. La forma hialino-vascular suele ser asintomática y localizada con mayor frecuencia en mediastino, mientras que la plasmo-celular se presenta frecuentemente con sintomatología sistémica y suele ser difusa o multicéntrica. Por lo poco frecuente de la asociación, presentamos un caso con antecedentes de anemia drepanocítica que después de 12 años de diagnóstico de una enfermedad de Castleman localizada, variante de células plasmáticas y exéresis total, hizo una recaída ganglionar con la misma variante, con buena respuesta clínica al tratamiento

Castleman's disease is a rare lymphoproliferative process characterized by benign hyperplasia of the lymph nodes. There are 2 distinct histologic variants: hyaline-vascular and cellular plasmodia, which in turn, may be localized or multicentric. The hyaline vascular form is usually asymptomatic and most often located in the mediastinum, whereas cellular plasmodia frequently presents with systemic symptoms and it is usually diffuse or multicentric. Due to the rarity of this association, we present a case with a history of sickle cell disease 12 years after diagnosis of localized Castleman's disease, plasma cell variant and total excision, lymph node had a relapse with the same variant, having good clinical treatment response

Lateral positioning at the dorsal midline: Slit and Roundabout receptors guide Drosophila heart cell migration.

Heart morphogenesis requires the coordinated regulation of cell movements and cell-cell interactions between distinct populations of cardiac precursor cells. Little is known about the mechanisms that organize cardiac cells into this complex structure. In this study, we analyzed the role of Slit, an extracellular matrix protein and its transmembrane receptors Roundabout (Robo) and Roundabout2 (Robo2) during morphogenesis of the Drosophila heart tube, a process analogous to early heart formation in vertebrates. During heart assembly, two types of progenitor cells align into rows and coordinately migrate to the dorsal midline of the embryo, where they merge to assemble a linear heart tube. Here we show that cardiac-specific expression of Slit is required to maintain adhesion between cells within each row during dorsal migration. Moreover, differential Robo expression determines the relative distance each row is positioned from the dorsal midline. The innermost CBs express only Robo, whereas the flanking pericardial cells express both receptors. Removal of robo2 causes pericardial cells to shift toward the midline, whereas ectopic robo2 in CBs drives them laterally, resulting in an unfused heart tube. We propose a model in which Slit has a dual role during assembly of the linear heart tube, functioning to regulate both cell positioning and adhesive interactions between migrating cardiac precursor cells.

Aspectos diagnósticos, evolutivos y terapéuticos de la mielofibrosis primaria / Diagnostic, evolutionary and therapeutic aspects of primary myelofibrosis

La mielofibrosis primaria se caracteriza por una expansión clonal de la célula madre hematopoyética con una proliferación reactiva no clonal de los fibroblastos y fibrosis de la médula ósea, por lo que ocurre una hematopoyesis extramedular. Por ser una enfermedad rara de la que no se han realizado investigaciones en nuestro medio, se caracterizaron los aspectos diagnósticos, terapéuticos y evolutivos en los pacientes atendidos en el Instituto de Hematología e Inmunología en el período comprendido entre noviembre de 1992 y mayo de 2009. La presentación fue más frecuente en el grupo de mayores de 60 años. El 80 por ciento de los pacientes presentaron síntomas al momento del diagnóstico. Los más frecuentes fueron las molestias en hipocondrio izquierdo, fiebre, sudoración nocturna y pérdida de peso. Los principales hallazgos en el hemograma al debut de la enfermedad, fueron la anemia y la trombocitosis, seguidos de conteos elevados de leucocitos con reacción leucoeritroblástica en el 80 por ciento de los casos. Se observaron cifras elevadas de la LDH en el 78,6 por ciento. En la biopsia de la médula ósea el 60 por ciento se hallaba en estadio prefibrático. Los pacientes fallecidos se encontraban en los grupos de mayor riesgo. La mediana de supervivencia fue de aproximadamente 5,5 años

Primary myelofibrosis is characterized by clonal expansion of hematopoietic stem cell with a non-reactive clonal proliferation of fibroblasts and bone marrow fibrosis, which occurs at an extramedullary hematopoiesis. Since it is a rare disease for which no research has been conducted in our environment, we charcterized the diagnostic aspects, treatment and evolution in patients treated at the Hematology and Immunology Institute during the period between November 1992 and May 2009. The most frequent presentation was in the group older than 60 years. 80 percent of patients had symptoms at diagnosis. The most frequent were the left upper quadrant discomfort, fever, night sweats and weight loss. The main findings in the blood count at this disease onset were anemia and thrombocytosis followed by high leukocyte counts with leukoerythroblastic reaction in 80 percent of cases. There were high levels of LDH 78.6 percent. The bone marrow biopsy was 60 percent pre fibrotic stage. Patients who died were in the highest risk groups. The median survival was approximately 5.5 years

Aspectos diagnósticos, evolutivos y terapéuticos de la mielofibrosis primaria / Diagnostic, evolutionary and therapeutic aspects of primary myelofibrosis

La mielofibrosis primaria se caracteriza por una expansión clonal de la célula madre hematopoyética con una proliferación reactiva no clonal de los fibroblastos y fibrosis de la médula ósea, por lo que ocurre una hematopoyesis extramedular. Por ser una enfermedad rara de la que no se han realizado investigaciones en nuestro medio, se caracterizaron los aspectos diagnósticos, terapéuticos y evolutivos en los pacientes atendidos en el Instituto de Hematología e Inmunología en el período comprendido entre noviembre de 1992 y mayo de 2009. La presentación fue más frecuente en el grupo de mayores de 60 años. El 80 por ciento de los pacientes presentaron síntomas al momento del diagnóstico. Los más frecuentes fueron las molestias en hipocondrio izquierdo, fiebre, sudoración nocturna y pérdida de peso. Los principales hallazgos en el hemograma al debut de la enfermedad, fueron la anemia y la trombocitosis, seguidos de conteos elevados de leucocitos con reacción leucoeritroblástica en el 80 por ciento de los casos. Se observaron cifras elevadas de la LDH en el 78,6 por ciento. En la biopsia de la médula ósea el 60 por ciento se hallaba en estadio prefibrático. Los pacientes fallecidos se encontraban en los grupos de mayor riesgo. La mediana de supervivencia fue de aproximadamente 5,5 años(AU)

Primary myelofibrosis is characterized by clonal expansion of hematopoietic stem cell with a non-reactive clonal proliferation of fibroblasts and bone marrow fibrosis, which occurs at an extramedullary hematopoiesis. Since it is a rare disease for which no research has been conducted in our environment, we charcterized the diagnostic aspects, treatment and evolution in patients treated at the Hematology and Immunology Institute during the period between November 1992 and May 2009. The most frequent presentation was in the group older than 60 years. 80 percent of patients had symptoms at diagnosis. The most frequent were the left upper quadrant discomfort, fever, night sweats and weight loss. The main findings in the blood count at this disease onset were anemia and thrombocytosis followed by high leukocyte counts with leukoerythroblastic reaction in 80 percent of cases. There were high levels of LDH 78.6 percent. The bone marrow biopsy was 60 percent pre fibrotic stage. Patients who died were in the highest risk groups. The median survival was approximately 5.5 years(AU)

Algunas variables clínicas y de laboratorio en pacientes adultos con leucemia mieloide crónica tratados con interferón alfa recombinante + citosina arabinósido / Some clinical and laboratory variables in adult patients with chronic myeloid leukemia treated with recombinant alpha interferon + cytosine arabinoside

La leucemia mieloide crónica del adulto es la hemopatía maligna más frecuente dentro de los síndromes mieloproliferativos. En un estudio retrospectivo longitudinal realizado entre enero de 1985 y diciembre de 2009, se evaluaron 46 pacientes en fase crónica atendidos en el Instituto de Hematología e Inmunología. Todos recibieron tratamiento inicial citorreductor y posteriormente interferón ? recombinante (INF?r) + citosina arabinósido. El 41,0 por ciento de los enfermos presentó un índice pronóstico de Sokal de alto riesgo. Las manifestaciones clínicas más frecuentes al diagnóstico fueron astenia (37 por ciento), esplenomegalia (31 por ciento) y pérdida de peso (28,3 por ciento). La respuesta hematológica parcial y completa fue del 26,8 por ciento y 65,9 por ciento a los 6 meses; la respuesta citogenética y molecular completa de 9,1 por ciento y 16,3 por ciento, respectivamente. Las reacciones adversas más frecuentes fueron fiebre (34,9 por ciento), trombocitopenia (26,2 por ciento) y síndrome general (23,8 por ciento). El 47,8 por ciento de los casos mostraron resistencia o intolerancia al INF?r y el 90,9 por ciento falleció por progresión de la enfermedad. La sobrevida global a los 5 años fue del 63,8 por ciento y la sobrevida libre de eventos a los 3 años fue del 68,9 por ciento. Según el índice pronóstico de Sokal, la sobrevida global mostró diferencia significativa entre los 3 grupos (p= 0,005), no así para la sobrevida libre de eventos (p= 0,165). El tratamiento con INF?r mostró resultados superiores a los de algunos países desarrollados y constituye una opción terapéutica eficaz en Cuba

Chronic myeloid leukemia is the most frequent myeloproliferative syndrome in adults. In a longitudinal retrospective study performed between January 1985 - December 2009, 46 patients in chronic phase diagnosed at the Institute of Hematology and Immunology were evaluated. They received cytoreductor agent as first treatment followed by interferon ?2 + cytosar. Forty one percent showed high risk Sokal prognosis score. The most frequent clinical manifestations at diagnosis were asthenia (37 percent), splenomegaly (31 percent) and weigh lost (28.3 percent). The partial and complete hematological response was of 26,8 percent and 65.9 percent after 6 months and the complete cytogenetic and molecular response was of 9.1 percent and 16.3 percent. The most frequent adverse reactions were: fever (34.9 percent), thrombocytopenia (26.3 percent) and general syndrome (23.8 percent). Resistance or intolerance to INF?2 was found in 47.8 percent of the patients and 90.0 percent died due to progression of the disease. The 5 year overall survival was of 63.8 percent and the 3 years free event survival was of 68.9 percent. According to Sokal prognosis score the overall survival showed significant difference between groups (p= 0.005) but there was no significant difference for free event survival (p= 0.165). The INF?2 treatment in our patients showed better results than those obtained in different developed countries and is an effective therapeutic option in Cuba

Algunas variables clínicas y de laboratorio en pacientes adultos con leucemia mieloide crónica tratados con interferón alfa recombinante + citosina arabinósido / Some clinical and laboratory variables in adult patients with chronic myeloid leukemia treated with recombinant alpha interferon + cytosine arabinoside

La leucemia mieloide crónica del adulto es la hemopatía maligna más frecuente dentro de los síndromes mieloproliferativos. En un estudio retrospectivo longitudinal realizado entre enero de 1985 y diciembre de 2009, se evaluaron 46 pacientes en fase crónica atendidos en el Instituto de Hematología e Inmunología. Todos recibieron tratamiento inicial citorreductor y posteriormente interferón ? recombinante (INF?r) + citosina arabinósido. El 41,0 por ciento de los enfermos presentó un índice pronóstico de Sokal de alto riesgo. Las manifestaciones clínicas más frecuentes al diagnóstico fueron astenia (37 por ciento), esplenomegalia (31 por ciento) y pérdida de peso (28,3 por ciento). La respuesta hematológica parcial y completa fue del 26,8 por ciento y 65,9 por ciento a los 6 meses; la respuesta citogenética y molecular completa de 9,1 por ciento y 16,3 por ciento, respectivamente. Las reacciones adversas más frecuentes fueron fiebre (34,9 por ciento), trombocitopenia (26,2 por ciento) y síndrome general (23,8 por ciento). El 47,8 por ciento de los casos mostraron resistencia o intolerancia al INF?r y el 90,9 por ciento falleció por progresión de la enfermedad. La sobrevida global a los 5 años fue del 63,8 por ciento y la sobrevida libre de eventos a los 3 años fue del 68,9 por ciento. Según el índice pronóstico de Sokal, la sobrevida global mostró diferencia significativa entre los 3 grupos (p= 0,005), no así para la sobrevida libre de eventos (p= 0,165). El tratamiento con INF?r mostró resultados superiores a los de algunos países desarrollados y constituye una opción terapéutica eficaz en Cuba(AU)

Chronic myeloid leukemia is the most frequent myeloproliferative syndrome in adults. In a longitudinal retrospective study performed between January 1985 - December 2009, 46 patients in chronic phase diagnosed at the Institute of Hematology and Immunology were evaluated. They received cytoreductor agent as first treatment followed by interferon ?2 + cytosar. Forty one percent showed high risk Sokal prognosis score. The most frequent clinical manifestations at diagnosis were asthenia (37 percent), splenomegaly (31 percent) and weigh lost (28.3 percent). The partial and complete hematological response was of 26,8 percent and 65.9 percent after 6 months and the complete cytogenetic and molecular response was of 9.1 percent and 16.3 percent. The most frequent adverse reactions were: fever (34.9 percent), thrombocytopenia (26.3 percent) and general syndrome (23.8 percent). Resistance or intolerance to INF?2 was found in 47.8 percent of the patients and 90.0 percent died due to progression of the disease. The 5 year overall survival was of 63.8 percent and the 3 years free event survival was of 68.9 percent. According to Sokal prognosis score the overall survival showed significant difference between groups (p= 0.005) but there was no significant difference for free event survival (p= 0.165). The INF?2 treatment in our patients showed better results than those obtained in different developed countries and is an effective therapeutic option in Cuba(AU)

Tumor de la órbita como forma poco común de presentación de un linfoma no hodgkiniano extranodal de la zona marginal / Orbit tumor as an uncommon way of presentation of a no-Hodgkin extranodal lymphoma of marginal zone

Los linfomas no hodgkinianos (LNH) representan la mitad de los tumores de la órbita, sin embargo, su incidencia en nuestro medio es poco frecuente. Se presenta una paciente de 52 años de edad, femenina, blanca, con antecedentes patológicos personales de hipertensión arterial, sin otros datos relevantes al interrogatorio, que acude a consulta por epífora y discreta ptosis palpebral del ojo derecho acompañada de tumoración dura y fija en zona ínfero medial de la órbita derecha. Las principales pruebas de laboratorio no mostraron nada relevante. En la resonancia magnética se comprobó tumoración de 2 × 1 cm, de contornos irregulares en relación con la pared posteroinferior de la órbita derecha. Se realizó biopsia de la lesión que se concluyó como un LNH con inmunofenotipo compatible con proceso linfoproliferativo de linfocitos B kappa. En la biopsia de médula ósea se informó infiltración nodular por proceso linfoproliferativo de bajo grado. Se concluyó el caso como un LNH primario de la órbita tipo zona marginal con expresión leucémica de células B monocitoides en estadio IVA. Se realizaron 8 ciclos de CHOP y se obtuvo respuesta parcial. Posteriormente se pasó a un esquema de segunda línea consistente en rituximab-fludarabina-ciclofosfamida-dexametasona, que se mantiene.

The no-Hodgkin lymphomas (NHL) accounted for the half of orbit tumor; however, its incidence in our environment is very uncommon. This is the case of a white female patient aged 52 with personal pathological backgrounds of high blood pressure without other relevant data in questioning, referred to consultation due to epiphora and a discrete palpebral ptosis of right eye accompanied by hard and fixed tumor in inferior medial of right orbita. Main laboratory tests were normal. In magnetic resonance (MR) it was demonstrated the presence of a 2 x 1 cm tumor with irregular borders in relation to posteroinferior wall of right orbit. A lesion biopsy was carried out with diagnosed as a primary NHL con immunophenotype compatible with a lymphoproliferative process. We conclude that this case is a primary orbit NHL of principal zone with leukemic expression of monocytic B cells in IVA state. We performed 8 cycles of CHOP with a partial response. Subsequently, we passed to a second-line maintained scheme consistent in Rituximab-Fludarabine-Cyclophosfamide-Dexamethasone.

Tumor de la órbita como forma poco común de presentación de un linfoma no hodgkiniano extranodal de la zona marginal / Orbit tumor as an uncommon way of presentation of a no-Hodgkin extranodal lymphoma of marginal zone

Los linfomas no hodgkinianos (LNH) representan la mitad de los tumores de la órbita, sin embargo, su incidencia en nuestro medio es poco frecuente. Se presenta una paciente de 52 años de edad, femenina, blanca, con antecedentes patológicos personales de hipertensión arterial, sin otros datos relevantes al interrogatorio, que acude a consulta por epífora y discreta ptosis palpebral del ojo derecho acompañada de tumoración dura y fija en zona ínfero medial de la órbita derecha. Las principales pruebas de laboratorio no mostraron nada relevante. En la resonancia magnética se comprobó tumoración de 2 × 1 cm, de contornos irregulares en relación con la pared posteroinferior de la órbita derecha. Se realizó biopsia de la lesión que se concluyó como un LNH con inmunofenotipo compatible con proceso linfoproliferativo de linfocitos B kappa. En la biopsia de médula ósea se informó infiltración nodular por proceso linfoproliferativo de bajo grado. Se concluyó el caso como un LNH primario de la órbita tipo zona marginal con expresión leucémica de células B monocitoides en estadio IVA. Se realizaron 8 ciclos de CHOP y se obtuvo respuesta parcial. Posteriormente se pasó a un esquema de segunda línea consistente en rituximab-fludarabina-ciclofosfamida-dexametasona, que se mantiene(AU)

The no-Hodgkin lymphomas (NHL) accounted for the half of orbit tumor; however, its incidence in our environment is very uncommon. This is the case of a white female patient aged 52 with personal pathological backgrounds of high blood pressure without other relevant data in questioning, referred to consultation due to epiphora and a discrete palpebral ptosis of right eye accompanied by hard and fixed tumor in inferior medial of right orbita. Main laboratory tests were normal. In magnetic resonance (MR) it was demonstrated the presence of a 2 x 1 cm tumor with irregular borders in relation to posteroinferior wall of right orbit. A lesion biopsy was carried out with diagnosed as a primary NHL con immunophenotype compatible with a lymphoproliferative process. We conclude that this case is a primary orbit NHL of principal zone with leukemic expression of monocytic B cells in IVA state. We performed 8 cycles of CHOP with a partial response. Subsequently, we passed to a second-line maintained scheme consistent in Rituximab-Fludarabine-Cyclophosfamide-Dexamethasone(AU)

Tratamiento de la mielofibrosis idiopática crónica con bajas dosis de talidomida: comunicación de 2 casos / Treatment of chronic idiopathic myelofibrosis with talidomide low doses: report of 2 cases

La mielofibrosis idiopática crónica (MIC), también conocida como metaplasia mieloide agnogénica, mielofibrosis primaria, mieloesclerosis con metaplasia mieloide, y mielofibrosis idiopática, se caracteriza por esplenomegalia, hematopoyesis extramedular, anemia progresiva, reacción leucoeritroblástica, hematíes en lágrimas en sangre periférica y fibrosis en médula ósea. Se han obtenido beneficios modestos con las terapias para la anemia (eritropoyetina y andrógenos) o la esplenomegalia (hidroxiurea, interferón-alfa). Ninguno de estos regímenes confiere un beneficio de supervivencia o cambio demostrable en la fibrosis intramedular. La ausencia de tratamiento eficaz para la enfermedad ha llevado al estudio de sus mecanismos patogénicos y el uso de nuevas alternativas terapéuticas. Se describen 2 pacientes con diagnóstico de MIC de 9 y 5 años de evolución que debido a los altos requerimientos transfusionales y la gran esplenomegalia, se les administró tratamiento con talidomida y prednisona. El tratamiento combinado logró aumento de las cifras de hemoglobina y de los conteos de plaquetas y una reducción y eliminacin de los requerimientos transfusionales(AU)

Chronic idiopathic myelofibrosis (CIM) also known as agnogenic myeloid metaplasia, primary myelosclerosis with myeloid metaplasia and idiopathic myelofibrosis is characterized by splenomegalia, extramedullary hematopoiesis, progressive anemia, leukoerythroblastosis reaction, tears white cells in peripheral blood and bone marrow fibrosis. There have been modest benefits with anemia therapies (erythropoietin and androgens) or the splenomegalia (hydroyurea, alpha-interferon). Neither of these regimes confers survival benefit or a demonstrable change in extramedullary fibrosis. The lack of an effectiveness treatment for this disease has leads us to study its pathogenic mechanisms and the use of new therapeutical alternatives. Two cases are described diagnosed with CIM with a course of 9 and 5 years and due to the high transfusion requirements and a significant splenomegalia it was necessary to administer a treatment with thalidomide and prednisone. Combination treatment achieved an increase in hemoglobin figures and of platelet counts and a decrease and elimination of transfusion requirements(AU)

Rituximab en leucemia linfocítica crónica en recaída y anemia hemolítica autoinmune: presentación de un caso / Use of Rituximab in recurrent chronic lymphocytic leukemia and autoimmune hemolytic anemia: a case presentation

La anemia hemolítica autoinmune es la manifestación inmunológica más frecuente en la leucemia linfocítica crónica (LLC) y se presenta entre el 10-20 por ciento de los casos. Su prevalencia está relacionada con el estadio y progresión de esta hemopatía, así como con el estado mutacional de los genes de la región variable de la cadena pesada de las inmunoglobulinas. Los corticosteroides constituyen la primera línea de tratamiento en esta anemia hemolítica autoinmune, pero solo la tercera parte de los pacientes responden y logran una remisión duradera, mientras que otros requieren tratamientos de mantenimiento o alternativos. Recientemente, se ha demostrado la efectividad del rituximab en el tratamiento de la anemia hemolítica autoinmune refractaria a la terapéutica esteroidea, incluso en los pacientes asociados con LLC. Se expone nuestra experiencia con el esquema R-COP (rituximab, ciclofosfamida, vincristina, prednisona) en el tratamiento de un paciente con LLC en recaída y anemia hemolítica autoinmune, que después de 20 meses de concluido este esquema se mantiene en remisión completa(AU)

The autoimmune hemolytic anemia is the more frequent immunologic manifestation in chronic lymphocytic leukemia (CLL) and it is present between 10-20 percent of cases. Its prevalence is related to stage and progression of this blood disease, as well as to mutation state of genes from the heavy chain variable region of immunoglobulins. The corticosteroids are the first line treatment in this autoimmune hemolytic anemia, but only the third part of patients responds and achieves a lasting remission, whereas others require support treatment or of alternative type. Recently, it has been shown the effectiveness of Rituximab in treatment of refractory autoimmune hemolytic anemia that after 20months of ended this scheme it is maintained in complete remission(AU)

Rituximab: historia, farmacología y perspectivas / Rituximab: history, pharmacology and perspectives

El rituximab integra la primera generación de anticuerpos monoclonales anti CD20 que se utiliza como terapia biológica en los síndromes linfoproliferativos crónicos de estirpe B, en enfermedades autoinmunes y en otras entidades donde hay proliferación de linfocitos B. Es un anticuerpo monoclonal quimérico murino/humano que se obtiene por ingeniería genética, con eficacia y seguridad probadas, y que se puede usar como monoterapia o combinado con quimioterapia. En esta revisión se exponen los antecedentes históricos, la farmacología y las perspectivas de este medicamento(AU)

The Rituximab tartrate is part of the first generation of anti-CD20 monoclonal antibodies used as biological therapy in stock 3 chronic lymphoproliferative syndromes, in autoimmune diseases, and in others entities where is present a B lymphocyte proliferation. It is a murine/human chimera monoclonal antibody obtained by genetic engineering, with a proven safety and effectiveness and that may be used as monotherapy or combined with chemotherapy. In present review are showed the historical backgrounds, the pharmacology and the perspectives of this drug(AU)