Characteristics and outcomes of adult patients in the PETHEMA registry with relapsed or refractory FLT3-ITD mutation-positive acute myeloid leukemia

This retrospective study investigated outcomes of 404 patients with relapsed/refractory (R/R) FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) acute myeloid leukemia (AML) enrolled in the PETHEMA registry, pre-approval of tyrosine kinase inhibitors. Most patients (63%) had received first-line intensive therapy with 3 + 7. Subsequently, patients received salvage with intensive therapy (n = 261), non-intensive therapy (n = 63) or supportive care only (n = 80). Active salvage therapy (i.e., intensive or non-intensive therapy) resulted in a complete remission (CR) or CR without hematological recovery (CRi) rate of 42%. More patients achieved a CR/CRi with intensive (48%) compared with non-intensive (19%) salvage therapy (p < 0.001). In the overall population, median overall survival (OS) was 5.5 months; 1- and 5-year OS rates were 25% and 7%. OS was significantly (p < 0.001) prolonged with intensive or non-intensive salvage therapy compared with supportive therapy, and in those achieving CR/CRi versus no responders. Of 280 evaluable patients, 61 (22%) had an allogeneic stem-cell transplant after they had achieved CR/CRi. In conclusion, in this large cohort study, salvage treatment approaches for patients with FLT3-ITD mutated R/R AML were heterogeneous. Median OS was poor with both non-intensive and intensive salvage therapy, with best long-term outcomes obtained in patients who achieved CR/CRi and subsequently underwent allogeneic stem-cell transplant.This study was supported by Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Valencia, Spain [CB16/12/00284]

Situación Fallot reparada en la edad adulta: resultados de 3 décadas de experiencia

Resumen: Introducción: Denominamos «situación Fallot» a una comunicación interventricular significativa con obstrucción a la salida del ventrículo derecho. Sin cirugía de reparación completa, excepcionalmente sobreviven hasta la edad adulta. Revisamos nuestra experiencia quirúrgica en estos adultos analizando sus resultados. Métodos: Indicamos reparación completa en adultos con situación Fallot no operados o solo paliados cuando sus ramas pulmonares tienen un tamaño aceptable. Estudiamos retrospectivamente 45 pacientes operados entre 1993-2022. Análisis estadístico: SPSS® 20.0. Resultados: Edad media: 37 ± 13 años, 53% varones, paliación previa 18%. Diagnósticos principales: ventrículo derecho bicameral + comunicación interventricular (60%), tetralogía de Fallot clásica (27%). Grado funcional NYHA: I 31%, II 38% y III 31%. Arritmia 20%. Hematocrito medio: 48 ± 10%. Asociaban agenesia de la arteria pulmonar izquierda un 7% e insuficiencia aórtica severa otro 7%. Indicación quirúrgica principal: estenosis pulmonar (98%). Las pruebas complementarias mostraban gradientes elevados entre ventrículo derecho-arteria pulmonar y buena contractilidad biventricular. Cirugía por esternotomía con circulación extracorpórea, hipotermia moderada y pinzado aórtico. Cierre de comunicación interventricular desde aurícula derecha (71%). Reconstrucción del tracto de salida derecho conservando válvula pulmonar (80%), interponiendo bioprótesis (16%) o parche transanular (4%). Cirugía asociada (18%): tricúspide (uno), aórtica (6), drenaje venoso pulmonar anómalo (uno). Mortalidad hospitalaria: un paciente (2,4%). Seguimiento medio 8,9 ± 7,6 años. Mortalidad tardía: 2 pacientes (4,5%). Reintervención en 7 pacientes (15%): 3 percutánea y 5 reoperados por lesiones residuales. Actualmente grado funcional i 68%, ii 28% y iii 4%, estando 83% en ritmo sinusal. Conclusiones: La reparación completa del adulto con situación Fallot logra mejoría clínica porque elimina la cianosis, cierra cortocircuitos intracardíacos y descarga de presión al ventrículo derecho. Nuestros resultados son excelentes, con elevadas tasas de conservación del anillo pulmonar, baja mortalidad y aceptable tasa de reintervención en el seguimiento posterior. Abstract: Introduction: We define “Fallot situation” as the existence of significant ventricular septal defect and right ventricular outflow obstruction. Survival into adulthood is extremely rare without complete surgical repair. We present our experience operating these adults. Methods: We consider complete surgical repair in Fallot adult patients if they have pulmonary arteries with adequate size. Retrospective study: 45 Fallot patients operated from 1993 to 2022 in our adult congenital heart unit. Statistical analysis: SPSS® 20.0. Results: Mean age: 37 ± 13 years, 53% male, 18% prior palliation. Principal diagnosis: double chamber right ventricle + ventricular septal defect (60%), tetralogy of Fallot (27%). NYHA functional class: i 31%, ii 38%, iii 31%. Arrhythmia 20%. Mean hematocrit: 48 ± 10%. Associated left pulmonary artery agenesis 7%, severe aortic regurgitation 7%. Main surgical indication was pulmonary stenosis 98%. Additional tests showed high gradients between the right ventricle and pulmonary artery, and good biventricular function. Surgeries were performed by median sternotomy with cardiopulmonary bypass, moderate hypothermia and aortic clamp. Ventricular septal defect was closed through the right atrium (71%). Reconstruction of the right ventricle outflow tract was done by preserving the pulmonary valve (80%), interposing bioprosthesis (16%), and using transannular patch (4%). Associated surgery (18%): tricuspid (one), aortic (6), anomalous pulmonary venous drainage (one). Inhospital mortality: one patient (2,2%). Mean follow-up: 8.9 ± 7.6 years. Late mortality: 2 patients (4.5%). Reintervention: 7 patients (15%) because of residual lesions (3 percutaneous, 5 surgical). Nowadays, functional class: i 68%, ii 28%, iii 4%; sinus rhythm 83%. Conclusions: Complete surgical repair in adulthood of Fallot patients achieves clinical improvement by eliminating the cyanosis, closing intracardiac shunts, and decreasing right ventricular pressure overload. Our results are excellent with good rates of pulmonary annulus preservation, low mortality and acceptable reintervention rate in the follow up

Operaciones inusuales en cirugía cardiaca infantil: resección de masas intracardiacas

Resumen: Introducción: Descubrir una masa intracardiaca en pediatría obliga a hacer un diagnóstico diferencial entre tumores (primarios/secundarios) y trombos, todos ellos infrecuentes en niños. Presentamos nuestra experiencia quirúrgica pediátrica de resección de masas intracardiacas. Métodos: Indicamos exéresis de la masa intracardiaca cuando causa síntomas o tiene repercusión hemodinámica por obstruir el flujo sanguíneo. Estudiamos retrospectivamente a 12 niños operados entre 2011-2022. Análisis estadístico: SPSS® v. 20.0. Resultados: Edad media: 7,1 ± 6 años (rango: 1 mes-15 años), 67% mujeres. Dos niños tenían cardiopatía congénita operada y 5 enfermedad oncológica; 2 presentaban coagulación alterada. Mayoritariamente (67%) asintomáticos y un 33% sintomáticos. Se realizó ecocardiograma en el 100% y resonancia cardiaca en el 50%: la masa obstructiva estaba localizada en la aurícula derecha en 6 pacientes, en la válvula tricúspide en 2, en el ventrículo derecho en 2 y en el ventrículo izquierdo en otros 2. Lesiones asociadas: foramen oval permeable (5), insuficiencia tricuspídea moderada (3) y estenosis pulmonar/subaórtica severa (2). Dos pacientes tenían tumor renal derecho con extensión intracardiaca por la cava inferior. Se realizó cirugía por esternotomía (11) o toracotomía (uno), con circulación extracorpórea (4 sin pinzar aorta), lográndose extirpar la masa completa (11) o parcialmente (uno). Tiempos medios de circulación extracorpórea y pinzado aórtico: 72 ± 44 y 34 ± 33 min, respectivamente. Intubación media 7 ± 7 h y estancia postoperatoria 11 ± 6 días. Dos pacientes presentaron complicaciones postoperatorias (ascitis y derrame pericárdico). Anatomía patológica de las masas explantadas: 4 trombos, 2 fibromas, 2 nefroblastomas, un mixoma, un rabdomioma, un fibroelastoma papilar y un pseudotumor inflamatorio. Sin mortalidad hospitalaria ni tardía. No hubo reoperaciones posteriores. Seguimiento medio 4,8 ± 3,7 años (máximo 10 años). Conclusiones: Recomendamos extirpar cualquier masa intracardiaca que obstruya significativamente el flujo sanguíneo o cause síntomas, para mejorar la clínica y filiar etiológicamente la masa. Nuestros resultados quirúrgicos son buenos, sin mortalidad ni reintervención en el seguimiento posterior. Abstract: Introduction: Discovering an intracardiac mass in pediatrics needs a differential diagnosis between tumours (primary/secondary) and thrombi, all being uncommon in children. We present our surgical experience resecting intracardiac masses in children. Methods: We indicate intracardiac mass excision when it causes symptoms or has hemodynamic consequences by obstructing blood flow. Retrospective study: 12 children operated from 2011 to 2022. Statistical analysis: SPSS® v. 20.0. Results: Mean age: 7,1 ± 6 years, 67% female. Two children had previous congenital heart disease repair and 5 oncologic pathology; 2 had anomalous coagulation test. Asymptomatic 67% and symptomatic 33%. Echocardiogram was performed in 100% and magnetic resonance in 50%: Obstructive mass located in the right atrium in 6 patients, tricuspid valve in 2, right ventricle in 2 and left ventricle in other 2. Associated lesions: patent foramen ovale (5), moderate tricuspid regurgitation (3) and severe pulmonary/subaortic stenosis (2). Two patients had a right renal tumor with intracardiac extension through the inferior vena cava. Surgery performed by sternotomy (11) or thoracotomy (one), with extracorporeal circulation (4 with beating heart), achieving removal of the whole mass (11) or partial (one). Mean extracorporeal circulation and aortic clamp times: 72 ± 44 and 34 ± 33 min, respectively. Mean intubation 7 ± 7 h and postoperative stay 11 ± 6 days. Two patients presented postoperative complications (ascites and pericardial effusion). Pathological anatomy of the explanted masses: 4 thrombi, 2 fibromas, 2 nephroblastomas, one myxoma, one rhabdomyoma, one papillary fibroelastoma and one inflammatory pseudotumor. No hospital or late mortality. No subsequent reoperations. Mean follow-up 4.8 ± 3.7 years (maximum 10 years). Conclusions: We recommend removing any intracardiac mass that significantly obstructs blood flow or causes symptoms, in order to improve clinically and determine the etiology of the mass. Our surgical results are good, without mortality or reintervention in subsequent follow-up

Characteristics and Outcomes of Adult Patients in the PETHEMA Registry with Relapsed or Refractory FLT3-ITD Mutation-Positive Acute Myeloid Leukemia

This retrospective study investigated outcomes of 404 patients with relapsed/refractory (R/R) FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) acute myeloid leukemia (AML) enrolled in the PETHEMA registry, pre-approval of tyrosine kinase inhibitors. Most patients (63%) had received first-line intensive therapy with 3 + 7. Subsequently, patients received salvage with intensive therapy (n = 261), non-intensive therapy (n = 63) or supportive care only (n = 80). Active salvage therapy (i.e., intensive or non-intensive therapy) resulted in a complete remission (CR) or CR without hematological recovery (CRi) rate of 42%. More patients achieved a CR/CRi with intensive (48%) compared with non-intensive (19%) salvage therapy (p < 0.001). In the overall population, median overall survival (OS) was 5.5 months; 1-and 5-year OS rates were 25% and 7%. OS was significantly (p <0.001) prolonged with intensive or non-intensive salvage therapy compared with supportive therapy, and in those achieving CR/CRi versus no responders. Of 280 evaluable patients, 61 (22%) had an allogeneic stem-cell transplant after they had achieved CR/CRi. In conclusion, in this large cohort study, salvage treatment approaches for patients with FLT3-ITD mutated R/R AML were heterogeneous. Median OS was poor with both non-intensive and intensive salvage therapy, with best long-term outcomes obtained in patients who achieved CR/CRi and subsequently underwent allogeneic stem-cell transplant

Cost-effectiveness of positive airway pressure modalities in obesity hypoventilation syndrome with severe obstructive sleep apnoea.

Obesity hypoventilation syndrome (OHS) is treated with either non-invasive ventilation (NIV) or CPAP, but there are no long-term cost-effectiveness studies comparing the two treatment modalities. We performed a large, multicentre, randomised, open-label controlled study to determine the comparative long-term cost and effectiveness of NIV versus CPAP in patients with OHS with severe obstructive sleep apnoea (OSA) using hospitalisation days as the primary outcome measure. Hospital resource utilisation and within trial costs were evaluated against the difference in effectiveness based on the primary outcome (hospitalisation days/year, transformed and non-transformed in monetary term). Costs and effectiveness were estimated from a log-normal distribution using a Bayesian approach. A secondary analysis by adherence subgroups was performed. In total, 363 patients were selected, 215 were randomised and 202 were available for the analysis. The median (IQR) follow-up was 3.01 (2.91-3.14) years for NIV group and 3.00 (2.92-3.17) years for CPAP. The mean (SD) Bayesian estimated hospital days was 2.13 (0.73) for CPAP and 1.89 (0.78) for NIV. The mean (SD) Bayesian estimated cost per patient/year in the NIV arm, excluding hospitalisation costs, was €2075.98 (91.6), which was higher than the cost in the CPAP arm of €1219.06 (52.3); mean difference €857.6 (105.5). CPAP was more cost-effective than NIV (99.5% probability) because longer hospital stay in the CPAP arm was compensated for by its lower costs. Similar findings were observed in the high and low adherence subgroups. CPAP is more cost-effective than NIV; therefore, CPAP should be the preferred treatment for patients with OHS with severe OSA. NCT01405976

Characteristics and outcomes of adult patients in the PETHEMA registry with relapsed or refractory FLT3-ITD mutation-positive acute myeloid leukemia

Simple Summary Most adult patients with acute myeloid leukemia (AML) relapse after achieving complete remission with chemotherapy; however, there is no standard second-line (salvage) treatment. We retrospectively investigated 404 patients aged >= 18 years with relapsed/refractory (R/R) AML with an FMS-like tyrosine kinase 3 (FLT3) mutation, treated at a PETHEMA (NCT02607059) site between 1998 and 2018. Patients received salvage treatment with intensive therapy (n = 261), non-intensive therapy (n = 63) or supportive care (n = 80). Complete remission was achieved by 48% of patients who received intensive therapy vs. 19% with non-intensive therapy. Intensive/non-intensive therapy prolonged overall survival significantly compared with supportive therapy. Of evaluable patients, 22% received an allogeneic stem-cell transplant after complete remission. The majority of patients with FLT3-mutated R/R AML received intensive salvage therapy, with the best outcomes being obtained when intensive salvage treatment was combined with stem-cell transplant. This retrospective study investigated outcomes of 404 patients with relapsed/refractory (R/R) FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) acute myeloid leukemia (AML) enrolled in the PETHEMA registry, pre-approval of tyrosine kinase inhibitors. Most patients (63%) had received first-line intensive therapy with 3 + 7. Subsequently, patients received salvage with intensive therapy (n = 261), non-intensive therapy (n = 63) or supportive care only (n = 80). Active salvage therapy (i.e., intensive or non-intensive therapy) resulted in a complete remission (CR) or CR without hematological recovery (CRi) rate of 42%. More patients achieved a CR/CRi with intensive (48%) compared with non-intensive (19%) salvage therapy (p < 0.001). In the overall population, median overall survival (OS) was 5.5 months; 1- and 5-year OS rates were 25% and 7%. OS was significantly (p < 0.001) prolonged with intensive or non-intensive salvage therapy compared with supportive therapy, and in those achieving CR/CRi versus no responders. Of 280 evaluable patients, 61 (22%) had an allogeneic stem-cell transplant after they had achieved CR/CRi. In conclusion, in this large cohort study, salvage treatment approaches for patients with FLT3-ITD mutated R/R AML were heterogeneous. Median OS was poor with both non-intensive and intensive salvage therapy, with best long-term outcomes obtained in patients who achieved CR/CRi and subsequently underwent allogeneic stem-cell transplant

Anales de Edafología y Agrobiología Tomo 44 Número 1-2

l. Suelos- Química. Caracterización de las distintas formas de materia orgánica fósil en dos canteras del cretácico superior de la provincia de Madrid, por G. Almendros, F. Martín, F. J. González Vila y C. Álvarez-Ramis.-- Interacción entre materiales orgánicos añadidos al suelo y su actividad ureásica, por Pérez Mateos, M. y González Carcedo, S.-- Suelos de la zona húmeda española XII.- Influencia de la hidromorfia en la composición mineralógica de suelos desarrollados sobre distintos materiales, por Villar Celorio, Ma C., Leirós de la Peña, Ma C. y Guitián Ojea, F.-- Adsorción de los herbicidas 2,4-D y 2,4,5-T por montmorillonita. II. Muestras homoiónicas de metales alcalinos, por Rodríguez-Pascual, C. y Hernández-Crespo, M. S.--Suelos- Biología. Descomposición de la hojarasca de Quercus rotundiolia Lam: y Quercus pyrenaica Willd. en monte adehesado, por A. Escudero Berian, M. V. Garrido Hernández y J. M. Gómez Gutiérrez.-- Influencia de la vegetación sobre las características de la materia orgánica de los suelos de la Alfaguara (Sierra de Alfacar-Granada), por García, l., Simón, M. y Polo, A.-- Suelos- Génesis. Caracterización edafogenética de los suelos halomorfos de un sector meridional de la Albufera de Elche (Alicante ), por R. Ortiz Silla, S. Hernández Carrascosa y F. Alcaraz Ariza.-- Suelos.- Fertilidad Efecto del glifosato sobre bacterias aerobias que colonizan un suelo arenoso, por M. A. Gómez y M. A. Sagardoy.-- Adsorción de n íquel por suelos calizos. Ajuste a las isotermas de Freundlich y FreundlichSibbesen, por M. T. Estañ, M. C. Bolarin y M. Romero.-- II. Biología Vegetal-Nutrición. Caracterización química y poder fertilizante de los lodos residuales de la planta depuradora de aguas de Santiago de Compostela, por Andrade Couce, M. L., Bao Iglesias, M., Fernández Fernández, C. J., Guitián Ojea, F.-- La calidad del agua de riego en el cultivo del limonero Verna, por A. Cerda, M. Caro, F. G. Fernández y M. G. Guillén.-- II. Biología Vegetal-Fisiología. Estudio de variedades de cereales resistentes al nematodo Heterodera Avenae Woll, por A. Sánchez, J. C. Sacristán y A. Bello.-- Diagnóstico de P, K, Ca y Mg en el trébol violeta: utilización de niveles de referencia y de la aproximación Dris, por J. Arines; R. Fábregas y Ma Jesús Sainz.-- Fertilización foliar con urea en plantas de soja (lycine max, L.), por E. O. Leidi y F. Nakayama.-- Composición en azúcares solubles de diferentes variedades de almendra (Prunus Amygdalus), por F. J. López Andreu, R. M. Esteban Alvarez y O. Carpena Artes.-- Alteraciones morfológicas y estructurales de cloroplastos de Fagus sylvatica L. en relación con la presencia de densas poblaciones liquenicas, por S. Rapsch y C. Ascaso.-- Acción de diferentes reguladores sobre la formación y crecimiento de callo en explantos de cotiledón de castaña cultivados in vitro, por Ma Luz González Caamaño.-- Tipificación y producción de comunidades de pastizal intensamente pastoreadas en la provincia de Salamanca (España), por A. Puerto, M. Rico, J. A. García Rodríguez y J. M. Gómez Gutiérrez.- Comunicaciones cortas. Comportamiento térmico del dimetoato retenido en diferentes óxidos metálicos, por Cristobal Valenzuela Calahorro y Alvaro Bernalte García.-- Aportación a la mejora de métodos de lavado de raíces, por l. Barrera J. M. Gómez Gutiérrez.-- NotasPeer reviewed2019-08.- CopyBook.- Libnova.- Biblioteca IC

Promoción turística sostenible de la reserva de la biosfera Tajo-Tejo Internacional

Convocatoria proyectos de innovación de Extremadura 2020/2021Se describe un proyecto llevado acabo por varios centros educativos ubicados en la zona de la Reserva de la Biosfera Tajo-Tejo Internacional (RBTTI) que pretendía contribuir a la transformación sostenible del entorno mediante su conocimiento y promoción, implementando las competencias digital, social y ciudadana y la cultura emprendedora mediante metodologías activas como el aprendizaje servicio. Entre los objetivos principales del proyecto destacan: dar a conocer las implicaciones de la RBTTI; diseñar una campaña de promoción de la RBTTI mediante trípticos y vídeos promocionales; conocer la Reserva a través de las principales vías pecuarias y caminos que comunican los pueblos; descubrir los principales elementos socioculturales, históricos y tradicionales de la Reserva; valorar la importancia del territorio para conservar la biodiversidad: paisajes, ecosistemas, fauna y flora representativa; relacionar la trashumancia y las vías pecuarias como rasgos identificativos de la Reserva, vinculándolo con la historia y rasgos culturales de los pueblos y valorar el emprendimiento y la iniciativa personal, el asosiacionismo y creación de redes de cooperación en y entre pueblos como motor de desarrolloExtremaduraES

Study design and rationale of the pAtients pResenTing with cOngenital heaRt dIseAse Register (ARTORIA‐R)

Aim: Due to improved therapy in childhood, many patients with congenital heart disease reach adulthood and are termed adults with congenital heart disease (ACHD). ACHD often develop heart failure (HF) as a consequence of initial palliative surgery or complex anatomy and subsequently require advanced HF therapy. ACHD are usually excluded from trials evaluating heart failure therapies, and in this context, more data about heart failure trajectories in ACHD are needed to guide the management of ACHD suffering from HF. ----- Methods and results: The pAtients pResenTing with cOngenital heaRt dIseAse Register (ARTORIA-R) will collect data from ACHD evaluated or listed for heart or heart-combined organ transplantation from 16 countries in Europe and the Asia/Pacific region. We plan retrospective collection of data from 1989-2020 and will include patients prospectively. Additional organizations and hospitals in charge of transplantation of ACHD will be asked in the future to contribute data to the register. The primary outcome is the combined endpoint of delisting due to clinical worsening or death on the waiting list. The secondary outcome is delisting due to clinical improvement while on the waiting list. All-cause mortality following transplantation will also be assessed. The data will be entered into an electronic database with access to the investigators participating in the register. All variables of the register reflect key components important for listing of the patients or assessing current HF treatment. ----- Conclusion: The ARTORIA-R will provide robust information on current management and outcomes of adults with congenital heart disease suffering from advanced heart failure