Long-term efficacy and safety results of taliglucerase alfa through 5years in adult treatment-naïve patients with Gaucher disease.

Taliglucerase alfa, the first available plant cell-expressed recombinant therapeutic protein, is an enzyme replacement therapy approved for Gaucher disease (GD). PB-06-001, a pivotal phase 3, multicenter, randomized, double-blind, parallel-dose study investigated taliglucerase alfa 30 or 60U/kg every other week through 9months in treatment-naïve adults with GD; 30-month extension study PB-06-003 followed. Patients completing PB-06-001 and PB-06-003 could continue treatment in PB-06-007. Nineteen patients enrolled in PB-06-007 (30U/kg, n=8; 60U/kg, n=9; dose adjusted, n=2); 17 completed 5 total years of treatment. In these 3 groups, respectively, taliglucerase alfa resulted in mean decreases in spleen volume (-8.7, -6.9, -12.4 multiples of normal), liver volume (-0.6, -0.4, -0.5 multiples of normal), chitotriosidase activity (-83.1%, -93.4%, -87.9%), and chemokine (CC motif) ligand 18 concentration (-66.7%, -83.3%, -78.9%), as well as mean increases in hemoglobin concentration (+2.1, +2.1, +1.8mg/dL) and platelet count (+31,871, +106,800, +34,000/mm3). The most common adverse events were nasopharyngitis and arthralgia. Most adverse events were mild/moderate; no serious adverse events were considered treatment-related. These results demonstrate continued improvement of disease parameters during 5years of taliglucerase alfa therapy in 17 treatment-naive patients with no new safety concerns, extending the taliglucerase alfa clinical efficacy and safety dataset. This study was registered at www.clinicaltrials.gov as NCT01422187.

Long-term efficacy and safety results of taliglucerase alfa up to 36 months in adult treatment-naïve patients with Gaucher disease.

Taliglucerase alfa is an intravenous enzyme replacement therapy approved for treatment of type 1 Gaucher disease (GD), and is the first available plant cell-expressed recombinant therapeutic protein. Herein, we report long-term safety and efficacy results of taliglucerase alfa in treatment-naïve adult patients with GD. Patients were randomized to receive taliglucerase alfa 30 or 60 U/kg every other week, and 23 patients completed 36 months of treatment. Taliglucerase alfa (30 U/kg; 60 U/kg, respectively) resulted in mean decreases in spleen volume (50.1%; 64.6%) and liver volume (25.6%; 24.4%) with mean increases in hemoglobin concentration (16.0%; 35.8%) and platelet count (45.7%; 114.0%), and mean decreases in chitotriosidase activity (71.5%; 82.2%). All treatment-related adverse events were mild to moderate in intensity and transient. The most common adverse events were nasopharyngitis, arthralgia, upper respiratory tract infection, headache, pain in extremity, and hypertension. These 36-month results of taliglucerase alfa in treatment-naïve adult patients with GD demonstrate continued improvement in disease parameters with no new safety concerns. These findings extend the taliglucerase alfa clinical safety and efficacy dataset. www.clinicaltrials.gov identifier NCT00705939. Am. J. Hematol. 91:656-660, 2016. © 2016 Wiley Periodicals, Inc.

High-Dimensional Feature Selection for Automatic Classification of Coronary Stenosis Using an Evolutionary Algorithm.

In this paper, a novel strategy to perform high-dimensional feature selection using an evolutionary algorithm for the automatic classification of coronary stenosis is introduced. The method involves a feature extraction stage to form a bank of 473 features considering different types such as intensity, texture and shape. The feature selection task is carried out on a high-dimensional feature bank, where the search space is denoted by O(2n) and n=473. The proposed evolutionary search strategy was compared in terms of the Jaccard coefficient and accuracy classification with different state-of-the-art methods. The highest feature selection rate, along with the best classification performance, was obtained with a subset of four features, representing a 99% discrimination rate. In the last stage, the feature subset was used as input to train a support vector machine using an independent testing set. The classification of coronary stenosis cases involves a binary classification type by considering positive and negative classes. The highest classification performance was obtained with the four-feature subset in terms of accuracy (0.86) and Jaccard coefficient (0.75) metrics. In addition, a second dataset containing 2788 instances was formed from a public image database, obtaining an accuracy of 0.89 and a Jaccard Coefficient of 0.80. Finally, based on the performance achieved with the four-feature subset, they can be suitable for use in a clinical decision support system.

[Mortality associated with myocardial damage by troponin I in patients with COVID 19]. / Mortalidad asociada a daño miocárdico mediante troponina I en pacientes con COVID-19.

Background: Coronavirus disease 2019 (COVID-19) can cause cardiac injury, probably associated with myocarditis and ischemia induced by the infection. Myocardial damage leads to the liberation of proinflammatory cytokines and to the activation of autoimmune adaptive mechanisms through molecular limitation. Objective: To assess mortality associated with myocardial damage in hospitalized patients with COVID-19 confirmed by troponin I measurement. Material and methods: Case-control study nested in a cohort of patients of a third-level hospital. Descriptive statistics were used to characterize the population. Qualitative variables were expressed as proportions and ranges, quantitative variables as means and standard deviation. Fisher's exact test was used to compare mortality between patients with and without myocardial damage. A p value < 0.05 was considered significant. Results: From June 2020 to August 2020, 28 patients who met the selection criteria were enrolled, out of which 15 had no myocardial damage and 13 had myocardial damage assessed by serum troponin measurement. A strong association was found between mortality and the presence of myocardial damage, since mortality was 20% (3/15) among patients without myocardial damage and 92.3% (12/13) among those with myocardial damage (Fisher's exact test, p < 0.005). Conclusion: Mortality in patients with COVID-19 is associated with myocardial damage assessed by troponin I measurement.

Introducción: la enfermedad por coronavirus del 2019 (COVID-19) puede causar lesión cardiaca, probablemente asociada con miocarditis e isquemias inducidas por la infección. El daño miocárdico conduce a la liberación de citocinas proinflamatorias y a la activación de mecanismos adaptativos de tipo autoinmune por medio de la limitación molecular. Objetivo: evaluar la mortalidad asociada a daño miocárdico en pacientes hospitalizados con COVID-19 confirmado mediante la medición de troponina I. Material y métodos: estudio de casos y controles anidado en una cohorte de los pacientes de un hospital de tercer nivel. Se utilizó estadística descriptiva para caracterizar a la población. Las variables cualitativas se expresaron como proporciones y rangos, las cuantitativas como medias y desviación estándar. Para comparar la mortalidad entre pacientes con y sin daño miocárdico se utilizó la prueba exacta de Fisher. Valores de p < 0.05 fueron significativos. Resultados: de junio del 2020 a agosto del 2020 se enrolaron 28 pacientes que cumplieron los criterios de selección, de los cuales 15 no tuvieron daño miocárdico y 13 tuvieron daño miocárdico evaluado con la medición de troponina sérica. Se encontró fuerte asociación entre la mortalidad y la presencia de daño miocárdico, ya que se registró mortalidad del 20% (3/15) entre los pacientes sin daño miocárdico y de 92.3% (12/13) entre los que tuvieron daño miocárdico (prueba exacta de Fisher: p < 0.005). Conclusiones: la mortalidad en pacientes con COVID-19 se asocia a daño miocárdico evaluado a través de la medición de troponina I.

[Systolic blood pressure reduction in patients with intracranial hemorrhage and functional prognosis]. / Reducción de la presión arterial sistólica en pacientes con hemorragia intracraneal y pronóstico funcional.

Background: Acute intracerebral hemorrhage affects annually more than 1 million people worldwide. Chronic systemic arterial hypertension is the most important modifiable risk factor for spontaneous intracerebral hemorrhage. Objective: To determine the relationship between the decrease in systolic blood pressure (SBP) in patients with intracranial hemorrhage and their short-term functional prognosis. Material and methods: Observational, longitudinal, prospective study in patients with intraparenchymal hemorrhage secondary to hypertensive dyscontrol, older than 18 years, of both sexes. Blood pressure was recorded at admission, every hour during the first 6 hours and every two hours from 8 to 24 hours after admission. Functionality was assessed using the modified Rankin scale at admission, at 6 and 24 hours after admission. Results: 58 patients were included, in whom the reduction of systolic blood pressure at admission was 17.04% and at 24 hours was 31.3 mm Hg; the mean systolic blood pressure was 183.62 mm Hg as opposed to 152.3 mm Hg at discharge (p < 0.001). Conclusions: In the first 6 hours, reduction in ASR is significantly associated with hospital outcome in patients with intracranial hemorrhage. A linear association was observed with improvement and favorable functional prognosis as measured by the modified Rankin scale.

Introducción: la hemorragia intracerebral aguda afecta anualmente a más de un millón de personas en todo el mundo. La hipertensión arterial sistémica crónica es el factor de riesgo modificable más importante para la hemorragia intracerebral espontánea. Objetivo: determinar la relación entre la disminución de la presión arterial sistólica (TAS) en pacientes con hemorragia intracraneal y su pronóstico funcional a corto plazo. Métodos: estudio observacional, longitudinal, prospectivo, en pacientes con hemorragia intraparenquimatosa secundaria a descontrol hipertensivo, mayores de 18 años, de ambos sexos. Se realizaron registros de presión arterial al ingreso, cada hora durante las primeras seis horas y cada dos horas desde las ocho a las 24 horas posterior al ingreso. Se evaluó funcionalidad mediante escala de Rankin modificada al ingreso, a las seis y a las 24 horas después del ingreso. Resultados: se incluyeron 58 pacientes, en quienes la reducción de la TAS al ingreso fue de 17.04% y a las 24 horas fue de 31.3 mm Hg de la presión arterial sistólica; la media de la TAS fue de 183.62 mm Hg a diferencia de la registrada al egreso, que fue de 152.3 mm Hg (p < 0.001). Conclusiones: en las primeras seis horas, la reducción de la TAS está significativamente asociada con el resultado hospitalario en pacientes con hemorragia intracraneal. Se observó una asociación lineal con la mejoría y un pronóstico funcional favorable, medido por la escala de Rankin modificada.

[Electrocardiographic interval as a predictor of life-threatening arrhythmias in dilated cardiomyopathy patients]. / Intervalo electrocardiográfico como predictor de arritmias graves en pacientes con miocardiopatía dilatada.

Background: The Tpe interval (Tp-e) in the surface electrocardiogram represents ventricular repolarization, a key phase in the pathogenesis of severe ventricular arrhythmias. However, there are few studies evaluating changes in this electrocardiographic interval as a risk factor for serious arrhythmias in patients with dilated cardiomyopathy. Objective: To determine whether the Tp-e interval prolongation predicts the presence of life-threatening arrhythmias in patients with dilated cardiomyopathy (DCM) with implantable cardioverter-defibrillator (ICD). Material and methods: Analytical, cross-sectional study in patients with DCM with ICDs. The Tp-e interval was measured in the V2 electrocardiographic lead and correlated with the incidence of life-threatening arrhythmias identified by the ICD. Results: 53 patients were recruited, 10 (18.8%) presented life-threatening arrhythmias. Prolongation of Tp-e interval was related to an increase in the incidence of ventricular tachycardia/fibrillation tachycardia (VT/FT) with a mean of 93 ± 20.5 ms (p = 0.003), using ROC curves to determine the thereshold of 90 ms for increased risk of VT/VF with sensitivity of 70% and specificity of 84%, with an area under the curve of 0.798. Conclusion: The prolongation of the ITp-e interval greater than 90 ms in a population with dilated cardiomyopathy predicts the presence of arrhythmic episodes, such as VT and/or VT/FT.

Introducción: el intervalo Tpe (ITp-e) en el electrocardiograma de superficie representa la repolarización ventricular, fase clave en la patogénesis de arritmias ventriculares graves. Sin embargo, existen pocos estudios que evalúen la alteración de este intervalo electrocardiográfico como factor de riesgo de arritmias graves en pacientes con miocardiopatía dilatada. Objetivo: determinar si la prolongación del ITp-e predice la presencia de arritmias potencialmente mortales en pacientes con miocardiopatía dilatada (MCD) portadores de desfibrilador automático implantable (DAI). Material y métodos: estudio, transversal analítico en pacientes con MCD portadores de DAI. Se midió el ITp-e en la derivación electrocardiográfica V2 y se correlacionó con la incidencia de arritmias potencialmente letales identificadas por el DAI. Resultados: se incluyeron 53 pacientes, 10 (18.8%) presentaron arritmias potencialmente mortales. La prolongación del ITp-e se relacionó con aumento de incidencia de taquicardia ventricular/fibrilación ventricular (TV/FV) con media de 93 ± 20.5 ms (p = 0.003), por lo que se determinó mediante curvas ROC el punto de corte de 90 ms para el aumento de riesgo de TV/FV con sensibilidad de 70% y especificidad de 84%, con área bajo la curva de 0.798. Conclusión: la prolongación del intervalo ITp-e > 90 ms en población con miocardiopatía dilatada predice la presencia de episodios arrítmicos como TV o FV.

[Atherogenic index and its association with acute coronary ischemic syndrome mortality]. / Índice aterogénico y su relación con la mortalidad del síndrome isquémico coronario agudo.

Background: Several indexes have been developed to define the risk attributable to lipid metabolism with a single value. The total cholesterol/high-density lipoprotein (TC/HDL-C) and low-density lipoprotein/high-density lipoprotein (LDL-C/HDL-C) ratios are the most used. The higher the value of these ratios, the greater the probability of cardiovascular events. Objective: To identify whether the TC/HDL-C and LDL-C/HDL-C ratios are early prognostic markers of mortality and major cardiovascular events in patients with ST-elevation acute coronary syndrome. Material and methods: 265 patients with ST-segment elevation acute coronary ischemic syndrome were included, divided into 4 groups according to the values of the atherogenic indices. Mortality and major cardiovascular events at 30-day follow-up were analyzed. Comparison of the groups was performed using the chi-squared test or ANOVA, depending on the case (p < 0.05). Results: The cut-off point for the TC/HDL-C index was 6.9 and for the LDL-C/HDL-C it was 2.7. The comparative analysis of groups showed that cardiovascular death and arrhythmia were higher in group 3 (p = 0.006 and p = 0.003, respectively). Conclusions: TC/HDL-C and LDL-C/HDL-C indexes can be used as prognostic markers of cardiovascular mortality in the first 30 days of follow-up.

Introducción: se han elaborado diferentes índices para definir el riesgo atribuible al metabolismo lipídico con un solo valor. Los coeficientes colesterol total/lipoproteínas de alta densidad (CT/C-HDL) y lipoproteínas de baja densidad/lipoproteínas de alta densidad (C-LDL/C-HDL) son los más utilizados. A mayor valor de estos cocientes, la probabilidad de eventos cardiovasculares es mayor. Objetivo: identificar si los índices CT/C-HDL y C-LDL/C-HDL son marcadores pronósticos tempranos de mortalidad y evento cardiovascular mayor en pacientes con síndrome isquémico coronario agudo con elevación del ST. Material y métodos: se incluyeron 265 pacientes con síndrome isquémico coronario agudo con elevación del segmento ST, divididos en 4 grupos según los valores de los índices aterogénicos. Se analizó la mortalidad y el evento cardiovascular mayor en los 30 días de seguimiento. Se identificó el punto de corte de cada índice mediante un análisis de curva ROC. La comparación de los grupos se hizo con chi cuadrada o ANOVA, según fuera el caso (p < 0.05). Resultados: el punto de corte para el índice CT/C-HDL fue de 6.9 y para el C-LDL/C-HDL de 2.7. El análisis comparativo de los grupos demostró que la muerte cardiovascular y arritmia fue mayor en el grupo 3 (p = 0.006 y p = 0.003, respectivamente). Conclusiones: los índices CT/C-HDL y C-LDL/C-HDL pueden ser utilizados como marcadores pronósticos de mortalidad cardiovascular en los primeros 30 días de seguimiento.

[Breast feeding and systemic blood pressure in infants]. / La alimentación al seno materno y la presión arterial sistémica en el lactante.

INTRODUCTION: Blood pressure levels in childhood influence these levels in adulthood, and breastfeeding has been considered such as a cardioprotective. We evaluated the association between blood pressure levels and feeding type in a group of infants. MATERIAL AND METHODS: We conducted a comparative cross-sectional study in term infants with appropriate weight at birth, to compare blood pressure levels in those children with exclusively breastfeeding, mixed-feeding and formula feeding. The comparison of groups was performed using ANOVA and multiple regression analysis was used to identify variables associated with mean arterial blood pressure levels. A p value < 0.05 was considered significant. RESULTS: We included 20 men and 24 women per group. Infant Formula Feeding had higher current weight and weight gain compared with the other two groups (p < 0.05). Systolic, diastolic and mean blood pressure levels, as well as respiratory and heart rate were higher in the groups of exclusively formula feeding and mixed-feeding than in those with exclusively breastfeeding (p < 0.05). Multiple regression analysis identified that variables associated with mean blood pressure levels were current body mass index, weight gain and formula feeding. CONCLUSIONS: Infants in breastfeeding show lower blood pressure, BMI and weight gain.

[Delta of neutrophil lymphocyte index and mortality in covid-19 disease]. / Delta del índice neutrófilo linfocito y mortalidad en infección COVID-19.

Background: Acute respiratory distress syndrome, due to SARS-CoV-2, is a worldwide health problem. The neutrophil-lymphocyte index allows risk stratification in patients with severe and poor prognostic data, since it reflects the inflammatory state. Objective: To determine whether the Neutrophil-Lymphocyte Index delta predicts mortality in patients with COVID-19. Material and methods: We conducted a longitudinal, comparative study in patients with COVID-19, older than 18 years, admitted to the ICU. We evaluated HAS, DM, obesity, COPD, asthma, PaO2/FiO2, tomographic severity. On admission and on days 3 and 7 we measured Neutrophil-Lymphocyte Index, SOFA and APACHE score. For statistical analysis, we performed ROC and Kaplan-Meyer curves. Results: We included 180 patients with COVID-19, 63 died (35%). Delta INL1(Day1-day3)>4.11 was associated with mortality (AUC:0.633); sensitivity 55.56% and specificity 77.78%, CI95 0.55-0.70, for delta INL2 (Day1-day7)>8.95 (AUC:0.623); sensitivity 44.44% and specificity 84.62%, CI95 0.54-0.69. Difference in survival was observed for Delta1. SOFA scale >6, was associated with more days of mechanical ventilation and lower PaO2/FiO2 (p<0.001). Conclusions: INL delta between the day of ICU admission and the 3rd day of evolution is a predictor of mortality in critically ill patients.

Introducción: El síndrome de dificultad respiratoria aguda, por SARS-CoV-2, es un problema mundial de salud. El índice neutrófilo-linfocito, permite estratificar el riesgo en pacientes con datos de severidad y mal pronóstico, ya que refleja el estado inflamatorio. Objetivo: Determinar si el delta del Índice Neutrófilo-Linfocito predice mortalidad en pacientes con COVID-19. Material y métodos: Se realizó un estudio longitudinal, comparativo en pacientes con COVID-19, mayores de 18 años, ingresados a UCI. Evaluamos HAS, DM, Obesidad, EPOC, asma, PaO2/FiO2, severidad tomográfica., A su ingreso y los días 3 y 7 medimos Índice Neutrófilo-Linfocito, puntaje SOFA y APACHE. En el análisis estadístico, realizamos curvas ROC y Kaplan-Meyer. Resultados: Incluimos 180 pacientes con COVID-19, 63 fallecieron (35%). Se asoció delta INL1(Día1-día3)>4.11 con mortalidad (AUC:0.633); sensibilidad 55.56% y especificidad 77.78%, IC95 0.55-0.70, para delta INL2 (Día1-día7)>8.95 (AUC:0.623); sensibilidad 44.44% y especificidad 84.62%, IC95 0.54-0.69. Se observó diferencia en la sobrevida para delta1. La escala SOFA >6, se asoció a más días de ventilación mecánica y PaO2/FiO2 menor (p<0.001). Conclusiones: El delta de INL entre el día de ingreso a UCI y el 3er día de evolución es predictor de mortalidad en pacientes críticamente enfermos.

Iron overload as cardiovascular risk factor in children and adolescents with renal disease.

BACKGROUND: Iron overload can affect cardiac structure and function by the production of free radicals in addition to iron deposits in heart muscle. The purpose of this study was to compare traditional and non-traditional cardiovascular risk factors (CVRF) in children and adolescents on renal replacement with and without iron overload. Also, we evaluated the relationships between iron overload and left ventricular mass (LVM). METHODS: First, in a cross-sectional study, we evaluated traditional and non-traditional CVRF in 143 children and adolescents, 48 on peritoneal dialysis (PD), 53 on hemodialysis (HD) and 42 after renal transplantation according to iron overload. In a second phase with a case-control study, we measured LVM in 12 case patients and 12 matched controls. RESULTS: Iron overload was identified in 15 patients (10.5%), 11 in HD and 4 in PD (P = 0.002). The group with iron overload had lower body mass index (17 versus 19; P = 0.01), total cholesterol (132 versus 165 mg/dL; P = 0.03) and hemoglobin (8.5 versus 10.6 g/dL; P = 0.003) but higher interleukin (IL)-6 levels (4.8 versus 3.6 ng/L; P = 0.04) and hypertension diagnosis (79 versus 48%; P < 0.001) than those without iron overload. Ferritin showed a positive correlation with C-reactive protein (CRP) and IL-6 levels. In a subgroup of 24 patients (12 with and 12 without iron overload), LVM was not different. However, ferritin levels showed a borderline positive correlation (r = 0.44, P = 0.05) with LVM. CONCLUSION: Children and adolescents with iron overload show more CVRFs, especially if they received replacement therapy with HD. Ferritin is related to CRP and IL-6 levels.

Hemodinámica renal en pacientes con obstrucción uretral: evaluación con ultrasonografía Doppler / Renal hemodynamics in patients with ureteral stenosis: evaluation with Doppler ultrasonography

Durante la obstrucción ureteral se presentan cambios en el flujo arterial al riñon afectado. Este estudio tuvo como finalidad determinar estos cambios mediante ultrasonografía Doppler de la arteria renal. Estas determinaciones se llevaron a cabo en seis unidades renales con obstrucción ureteral, en las seis unidades renales contralaterales a la obstruida y en 14 unidades renales testigos. Se encontró que las características de flujo de la arteria renal manifestaban diferencias estadísticamente significativas entre la unidad renal obstruida y las unidades renales contralaterales y testigos