Impact of FLT3–ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study

FLT3–ITD results in a poor prognosis in terms of overall survival (OS) and relapse-free survival (RFS) in acute myeloid leukemia (AML). However, the prognostic usefulness of the allelic ratio (AR) to select post-remission therapy remains controversial. Our study focuses on the prognostic impact of FLT3–ITD and its ratio in a series of 2901 adult patients treated intensively in the pre-FLT3 inhibitor era and reported in the PETHEMA registry. A total of 579 of these patients (20%) harbored FLT3–ITD mutations. In multivariate analyses, patients with an FLT3–ITD allele ratio (AR) of >0.5 showed a lower complete remission (CR rate) and OS (HR 1.47, p = 0.009), while AR > 0.8 was associated with poorer RFS (HR 2.1; p 0.5). Using the maximally selected log-rank statistics, we established an optimal cutoff of FLT3–ITD AR of 0.44 for OS, and 0.8 for RFS. We analyzed the OS and RFS according to FLT3–ITD status in all patients, and we found that the group of FLT3–ITD-positive patients with AR 0.44, allo-HSCT was superior to auto-HSCT in terms of OS and RFS. This study provides more evidence for a better characterization of patients with AML harboring FLT3–ITD mutations.Depto. de MedicinaFac. de MedicinaTRUEInstituto de Salud Carlos IIIFundación CRIS Contra el CáncerInstituto de Investigación Hospital 12 de OctubreUnión Europeapu

Impact of FLT3–ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study

FLT3–ITD results in a poor prognosis in terms of overall survival (OS) and relapse-free survival (RFS) in acute myeloid leukemia (AML). However, the prognostic usefulness of the allelic ratio (AR) to select post-remission therapy remains controversial. Our study focuses on the prognostic impact of FLT3–ITD and its ratio in a series of 2901 adult patients treated intensively in the pre-FLT3 inhibitor era and reported in the PETHEMA registry. A total of 579 of these patients (20%) harbored FLT3–ITD mutations. In multivariate analyses, patients with an FLT3–ITD allele ratio (AR) of >0.5 showed a lower complete remission (CR rate) and OS (HR 1.47, p = 0.009), while AR > 0.8 was associated with poorer RFS (HR 2.1; p 0.5). Using the maximally selected log-rank statistics, we established an optimal cutoff of FLT3–ITD AR of 0.44 for OS, and 0.8 for RFS. We analyzed the OS and RFS according to FLT3–ITD status in all patients, and we found that the group of FLT3–ITD-positive patients with AR 0.44, allo-HSCT was superior to auto-HSCT in terms of OS and RFS. This study provides more evidence for a better characterization of patients with AML harboring FLT3–ITD mutations.This study was fundedby Instituto de Salud Carlos III (ISCIII) through the project PI19/01518 and PI19/00730 and co- funded by the European Union, the CRIS Against Cancer Foundation, grant 2018/001, and by the Instituto de Investigación Hospital 12 de Octubre (IMAS12). APeer reviewe

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Impacto de los síndromes geriátricos en el manejo y pronóstico del paciente anciano con enfermedad cardiovascular

El envejecimiento poblacional y la alta incidencia de enfermedad cardiovascular en el anciano hace de este tema un problema de salud pública de primera magnitud. El primer bloque de este proyecto analiza las causas del manejo conservador en pacientes con estenosis aórtica (EAo) grave sintomática en nuestro medio, las características y pronóstico de estos pacientes en función del motivo del manejo conservador. Para ello, se incluyeron los pacientes con EAo grave sintomática no intervenidos del registro Influencia del Diagnóstico de Estenosis Aórtica Severa (IDEAS) (n=292). Se dividieron en 5 grupos en función del motivo de manejo conservador: grupo I (comorbilidad) con 128 pacientes (43,8%); grupo II (demencia) con 18 (6,2%); grupo III (edad avanzada) con 34 (11,6%); grupo IV (rechazo por parte del paciente) con 62 (21,2%) y grupo V (otras razones) con 50 (17,1%). Se apreció una mayor comorbilidad en el grupo I y un mayor riesgo quirúrgico, así como mayor mortalidad al año (42,2%), con mayor frecuencia extracardíaca. En contraste, los pacientes del grupo III tenían menos comorbilidades y menor mortalidad (20,6%). El segundo bloque del proyecto analiza el impacto de la comorbilidad (Índice de Charlson (IdC)]) en el manejo y pronóstico de los pacientes nonagenarios con EAo (n=177) procedentes de los registros IDEAS y Pronóstico de la Estenosis Grave Aórtica Síntomática del Octogenario (PEGASO). Un total de 56 pacientes (31,6%) tenían un grado de comorbilidad bajo (IdC <3). Se apreció una potente asociación entre el grado de comorbilidad y la mortalidad al año (p<0,001). De todos los pacientes, 150 (84,7%) fueron tratados de forma conservadora. Los predictores de tratamiento conservador fueron: 1) manejo en hospitales sin disponibilidad de implantación transcatéter de válvula aórtica (TAVI) (p< 0,001); 2) menor clase funcional de la New York Heart Association (NYHA) (p=0,012) y 3) menor gradiente transaórtico medio (p=0,048). El manejo no estuvo condicionado por el grado de comorbilidad. La última parte del proyecto analiza en ancianos consecutivos con infarto de miocardio, la prevalencia de bloqueo interaricular (BIA), su asociación con la fragilidad y otros síndromes geriátricos y su asociación con la incidencia de fibrilación auricular (FA) al año. Se incluyeron 254 pacientes. De de los pacientes en ritmo sinusal, 149 presentaban una conducción interauricular normal (67,7%); 37, BIA parcial (16,8%) y 34, BIA avanzado (15,5%). Se apreció una asociación lineal significativa entre el grado de BIA y la prevalencia de hipertensión, ictus previo e insuficiencia mitral. Se apreció una tendencia lineal no significativa entre la prevalencia de fragilidad y el grado de BIA, sin asociación con el resto de síndromes geriátricos. Se apreció asimismo una tendencia no significativa hacia una mayor incidencia de FA o mortalidad en los pacientes con BIA avanzado (razón de riesgos 1,51, intervalo de confianza del 95% 0,85-2,70, p=0,164). Conclusiones: a) Los pacientes con EAo grave sintomática tratados de forma conservadora constituyen un grupo heterogéneo. Los pacientes rechazados por edad avanzada tenían menos comorbilidades y riesgo quirúrgico, así como una mejor evolución. b) Los pacientes nonagenarios con EAo grave son tratados de forma conservadora en casi el 85% de los casos. A pesar de la intensa asociación entre el grado de comorbilidad y el pronóstico, el manejo clínico no estuvo condicionado por el grado de comorbilidad. c) Alrededor de un tercio de los ancianos con infarto de miocardio en ritmo sinusal presentan BIA en el ECG. Los datos apoyan la hipótesis del BIA como un estado previo a la FA. Se apreció una tendencia lineal no significativa entre la prevalencia de fragilidad y el grado de BIA. El BIA avanzado se asoció con una tendencia a mayor incidencia de muerte o FA al año.The progressive aging population and the high incidence of cardiovascular disease in the elderly make this issue a major public health problem. First, we analyzed the causes of conservative management in patients with severe aortic stenosis (AS), as well as clinical characteristics and prognosis of these patients according to the reason for conservative management. We included all patients with symptomatic severe AS conservatively managed from the Influencia del Diagnóstico de Estenosis Aórtica Severa (IDEAS) registry (n=292). The main reasons for conservative management were: group I (comorbidity) in 128 patients (43.8%); group II (dementia) in 18 (6.2%); group III (advanced age) in 34 (11.6%); group IV (rejection by the patient) in 62 (21.2%) and group V (other reasons) in 50 (17.1%). There was a greater comorbidity burden and a higher surgical risk in group I, as well as a higher rate of mortality at one year (42.2%), more commonly due to non cardiac causes. In contrast, patients from group III had fewer comorbidities and lower mortality (20.6%). Secondly, we analyzed the impact of comorbidity as measured by the Charlson Index (CI) on the management and prognosis of nonagenarian patients with AS (n=177) from the IDEAS and Pronóstico de la Estenosis Grave Aórtica Síntomática del Octogenario (PEGASO) registries. A total of 56 patients (31.6%) had a low degree of comorbidity (CI <3). A strong association was observed between the degree of comorbidity and mortality at one year (p <0.001). Most patients (150/177, 84.7%) were managed conservatively. Predictors of conservative management were hospital management without TAVI facilities (p <0.001); lower functional class (p = 0.012) and lower mean transaortic gradient (p = 0.048). Management was not different according to the degree of comorbidity. Finally, we analyzed the prevalence of interatrial block (IAB), its association with frailty and other geriatric syndromes and its association with the incidence of atrial fibrillation (AF) at one year in consecutive elderly patients with myocardial infarction. We included 254 patients. Among patients in sinus rhythm, 149 presented a normal interatrial conduction (67.7%), 37 partial IAB (16.8%) and 34 advanced IAB (15.5%). There was a significant linear association between the degree of IAB and the prevalence of hypertension, previous stroke and mitral regurgitation. A non-significant linear trend was observed between the prevalence of frailty and the degree of IAB, without association with the rest of geriatric syndromes. A non-significant trend towards a higher incidence of AF or mortality in patients with advanced BIA in sinus rhythm (hazard ratio 1.51, 95% confidence interval 0.85-2.70, p = 0.164). Conclusions: a) Patients with symptomatic severe AS managed conservatively are a heterogeneous group. The patients rejected because of advanced age had lower comobidity and surgical risk, as well as a better clinical outcomes. b) Nonagenarians with severe AS are managed conservatively in almost 85% of cases. Despite the strong association between the degree of comorbidity and prognosis, clinical management was not different according to the degree of comorbidity. c) About one third of elderly patients with myocardial infarction presented BIA on the ECG. The data support the hypothesis that BIA is a pre-AF state. A non-significant linear trend was observed between the prevalence of frailty and the degree of IAB. Advanced BIA was associated with a trend towards a higher incidence of AF or death at one year

Impacto de los síndromes geriátricos en el manejo y pronóstico del paciente anciano con enfermedad cardiovascular

El envejecimiento poblacional y la alta incidencia de enfermedad cardiovascular en el anciano hace de este tema un problema de salud pública de primera magnitud. El primer bloque de este proyecto analiza las causas del manejo conservador en pacientes con estenosis aórtica (EAo) grave sintomática en nuestro medio, las características y pronóstico de estos pacientes en función del motivo del manejo conservador. Para ello, se incluyeron los pacientes con EAo grave sintomática no intervenidos del registro Influencia del Diagnóstico de Estenosis Aórtica Severa (IDEAS) (n=292). Se dividieron en 5 grupos en función del motivo de manejo conservador: grupo I (comorbilidad) con 128 pacientes (43,8%); grupo II (demencia) con 18 (6,2%); grupo III (edad avanzada) con 34 (11,6%); grupo IV (rechazo por parte del paciente) con 62 (21,2%) y grupo V (otras razones) con 50 (17,1%). Se apreció una mayor comorbilidad en el grupo I y un mayor riesgo quirúrgico, así como mayor mortalidad al año (42,2%), con mayor frecuencia extracardíaca. En contraste, los pacientes del grupo III tenían menos comorbilidades y menor mortalidad (20,6%). El segundo bloque del proyecto analiza el impacto de la comorbilidad (Índice de Charlson (IdC)]) en el manejo y pronóstico de los pacientes nonagenarios con EAo (n=177) procedentes de los registros IDEAS y Pronóstico de la Estenosis Grave Aórtica Síntomática del Octogenario (PEGASO). Un total de 56 pacientes (31,6%) tenían un grado de comorbilidad bajo (IdC <3). Se apreció una potente asociación entre el grado de comorbilidad y la mortalidad al año (p<0,001). De todos los pacientes, 150 (84,7%) fueron tratados de forma conservadora. Los predictores de tratamiento conservador fueron: 1) manejo en hospitales sin disponibilidad de implantación transcatéter de válvula aórtica (TAVI) (p< 0,001); 2) menor clase funcional de la New York Heart Association (NYHA) (p=0,012) y 3) menor gradiente transaórtico medio (p=0,048). El manejo no estuvo condicionado por el grado de comorbilidad. La última parte del proyecto analiza en ancianos consecutivos con infarto de miocardio, la prevalencia de bloqueo interaricular (BIA), su asociación con la fragilidad y otros síndromes geriátricos y su asociación con la incidencia de fibrilación auricular (FA) al año. Se incluyeron 254 pacientes. De de los pacientes en ritmo sinusal, 149 presentaban una conducción interauricular normal (67,7%); 37, BIA parcial (16,8%) y 34, BIA avanzado (15,5%). Se apreció una asociación lineal significativa entre el grado de BIA y la prevalencia de hipertensión, ictus previo e insuficiencia mitral. Se apreció una tendencia lineal no significativa entre la prevalencia de fragilidad y el grado de BIA, sin asociación con el resto de síndromes geriátricos. Se apreció asimismo una tendencia no significativa hacia una mayor incidencia de FA o mortalidad en los pacientes con BIA avanzado (razón de riesgos 1,51, intervalo de confianza del 95% 0,85-2,70, p=0,164). Conclusiones: a) Los pacientes con EAo grave sintomática tratados de forma conservadora constituyen un grupo heterogéneo. Los pacientes rechazados por edad avanzada tenían menos comorbilidades y riesgo quirúrgico, así como una mejor evolución. b) Los pacientes nonagenarios con EAo grave son tratados de forma conservadora en casi el 85% de los casos. A pesar de la intensa asociación entre el grado de comorbilidad y el pronóstico, el manejo clínico no estuvo condicionado por el grado de comorbilidad. c) Alrededor de un tercio de los ancianos con infarto de miocardio en ritmo sinusal presentan BIA en el ECG. Los datos apoyan la hipótesis del BIA como un estado previo a la FA. Se apreció una tendencia lineal no significativa entre la prevalencia de fragilidad y el grado de BIA. El BIA avanzado se asoció con una tendencia a mayor incidencia de muerte o FA al año.The progressive aging population and the high incidence of cardiovascular disease in the elderly make this issue a major public health problem. First, we analyzed the causes of conservative management in patients with severe aortic stenosis (AS), as well as clinical characteristics and prognosis of these patients according to the reason for conservative management. We included all patients with symptomatic severe AS conservatively managed from the Influencia del Diagnóstico de Estenosis Aórtica Severa (IDEAS) registry (n=292). The main reasons for conservative management were: group I (comorbidity) in 128 patients (43.8%); group II (dementia) in 18 (6.2%); group III (advanced age) in 34 (11.6%); group IV (rejection by the patient) in 62 (21.2%) and group V (other reasons) in 50 (17.1%). There was a greater comorbidity burden and a higher surgical risk in group I, as well as a higher rate of mortality at one year (42.2%), more commonly due to non cardiac causes. In contrast, patients from group III had fewer comorbidities and lower mortality (20.6%). Secondly, we analyzed the impact of comorbidity as measured by the Charlson Index (CI) on the management and prognosis of nonagenarian patients with AS (n=177) from the IDEAS and Pronóstico de la Estenosis Grave Aórtica Síntomática del Octogenario (PEGASO) registries. A total of 56 patients (31.6%) had a low degree of comorbidity (CI <3). A strong association was observed between the degree of comorbidity and mortality at one year (p <0.001). Most patients (150/177, 84.7%) were managed conservatively. Predictors of conservative management were hospital management without TAVI facilities (p <0.001); lower functional class (p = 0.012) and lower mean transaortic gradient (p = 0.048). Management was not different according to the degree of comorbidity. Finally, we analyzed the prevalence of interatrial block (IAB), its association with frailty and other geriatric syndromes and its association with the incidence of atrial fibrillation (AF) at one year in consecutive elderly patients with myocardial infarction. We included 254 patients. Among patients in sinus rhythm, 149 presented a normal interatrial conduction (67.7%), 37 partial IAB (16.8%) and 34 advanced IAB (15.5%). There was a significant linear association between the degree of IAB and the prevalence of hypertension, previous stroke and mitral regurgitation. A non-significant linear trend was observed between the prevalence of frailty and the degree of IAB, without association with the rest of geriatric syndromes. A non-significant trend towards a higher incidence of AF or mortality in patients with advanced BIA in sinus rhythm (hazard ratio 1.51, 95% confidence interval 0.85-2.70, p = 0.164). Conclusions: a) Patients with symptomatic severe AS managed conservatively are a heterogeneous group. The patients rejected because of advanced age had lower comobidity and surgical risk, as well as a better clinical outcomes. b) Nonagenarians with severe AS are managed conservatively in almost 85% of cases. Despite the strong association between the degree of comorbidity and prognosis, clinical management was not different according to the degree of comorbidity. c) About one third of elderly patients with myocardial infarction presented BIA on the ECG. The data support the hypothesis that BIA is a pre-AF state. A non-significant linear trend was observed between the prevalence of frailty and the degree of IAB. Advanced BIA was associated with a trend towards a higher incidence of AF or death at one year

Impacto de los síndromes geriátricos en el manejo y pronóstico del paciente anciano con enfermedad cardiovascular /

El envejecimiento poblacional y la alta incidencia de enfermedad cardiovascular en el anciano hace de este tema un problema de salud pública de primera magnitud. El primer bloque de este proyecto analiza las causas del manejo conservador en pacientes con estenosis aórtica (EAo) grave sintomática en nuestro medio, las características y pronóstico de estos pacientes en función del motivo del manejo conservador. Para ello, se incluyeron los pacientes con EAo grave sintomática no intervenidos del registro Influencia del Diagnóstico de Estenosis Aórtica Severa (IDEAS) (n=292). Se dividieron en 5 grupos en función del motivo de manejo conservador: grupo I (comorbilidad) con 128 pacientes (43,8%); grupo II (demencia) con 18 (6,2%); grupo III (edad avanzada) con 34 (11,6%); grupo IV (rechazo por parte del paciente) con 62 (21,2%) y grupo V (otras razones) con 50 (17,1%). Se apreció una mayor comorbilidad en el grupo I y un mayor riesgo quirúrgico, así como mayor mortalidad al año (42,2%), con mayor frecuencia extracardíaca. En contraste, los pacientes del grupo III tenían menos comorbilidades y menor mortalidad (20,6%). El segundo bloque del proyecto analiza el impacto de la comorbilidad (Índice de Charlson (IdC)]) en el manejo y pronóstico de los pacientes nonagenarios con EAo (n=177) procedentes de los registros IDEAS y Pronóstico de la Estenosis Grave Aórtica Síntomática del Octogenario (PEGASO). Un total de 56 pacientes (31,6%) tenían un grado de comorbilidad bajo (IdC 3). Se apreció una potente asociación entre el grado de comorbilidad y la mortalidad al año (p 0,001). De todos los pacientes, 150 (84,7%) fueron tratados de forma conservadora. Los predictores de tratamiento conservador fueron: 1) manejo en hospitales sin disponibilidad de implantación transcatéter de válvula aórtica (TAVI) (p 0,001); 2) menor clase funcional de la New York Heart Association (NYHA) (p=0,012) y 3) menor gradiente transaórtico medio (p=0,048). El manejo no estuvo condicionado por el grado de comorbilidad. La última parte del proyecto analiza en ancianos consecutivos con infarto de miocardio, la prevalencia de bloqueo interaricular (BIA), su asociación con la fragilidad y otros síndromes geriátricos y su asociación con la incidencia de fibrilación auricular (FA) al año. Se incluyeron 254 pacientes. De de los pacientes en ritmo sinusal, 149 presentaban una conducción interauricular normal (67,7%); 37, BIA parcial (16,8%) y 34, BIA avanzado (15,5%). Se apreció una asociación lineal significativa entre el grado de BIA y la prevalencia de hipertensión, ictus previo e insuficiencia mitral. Se apreció una tendencia lineal no significativa entre la prevalencia de fragilidad y el grado de BIA, sin asociación con el resto de síndromes geriátricos. Se apreció asimismo una tendencia no significativa hacia una mayor incidencia de FA o mortalidad en los pacientes con BIA avanzado (razón de riesgos 1,51, intervalo de confianza del 95% 0,85-2,70, p=0,164). Conclusiones: a) Los pacientes con EAo grave sintomática tratados de forma conservadora constituyen un grupo heterogéneo. Los pacientes rechazados por edad avanzada tenían menos comorbilidades y riesgo quirúrgico, así como una mejor evolución. b) Los pacientes nonagenarios con EAo grave son tratados de forma conservadora en casi el 85% de los casos. A pesar de la intensa asociación entre el grado de comorbilidad y el pronóstico, el manejo clínico no estuvo condicionado por el grado de comorbilidad. c) Alrededor de un tercio de los ancianos con infarto de miocardio en ritmo sinusal presentan BIA en el ECG. Los datos apoyan la hipótesis del BIA como un estado previo a la FA. Se apreció una tendencia lineal no significativa entre la prevalencia de fragilidad y el grado de BIA. El BIA avanzado se asoció con una tendencia a mayor incidencia de muerte o FA al año.The progressive aging population and the high incidence of cardiovascular disease in the elderly make this issue a major public health problem. First, we analyzed the causes of conservative management in patients with severe aortic stenosis (AS), as well as clinical characteristics and prognosis of these patients according to the reason for conservative management. We included all patients with symptomatic severe AS conservatively managed from the Influencia del Diagnóstico de Estenosis Aórtica Severa (IDEAS) registry (n=292). The main reasons for conservative management were: group I (comorbidity) in 128 patients (43.8%); group II (dementia) in 18 (6.2%); group III (advanced age) in 34 (11.6%); group IV (rejection by the patient) in 62 (21.2%) and group V (other reasons) in 50 (17.1%). There was a greater comorbidity burden and a higher surgical risk in group I, as well as a higher rate of mortality at one year (42.2%), more commonly due to non cardiac causes. In contrast, patients from group III had fewer comorbidities and lower mortality (20.6%). Secondly, we analyzed the impact of comorbidity as measured by the Charlson Index (CI) on the management and prognosis of nonagenarian patients with AS (n=177) from the IDEAS and Pronóstico de la Estenosis Grave Aórtica Síntomática del Octogenario (PEGASO) registries. A total of 56 patients (31.6%) had a low degree of comorbidity (CI 3). A strong association was observed between the degree of comorbidity and mortality at one year (p 0.001). Most patients (150/177, 84.7%) were managed conservatively. Predictors of conservative management were hospital management without TAVI facilities (p 0.001); lower functional class (p = 0.012) and lower mean transaortic gradient (p = 0.048). Management was not different according to the degree of comorbidity. Finally, we analyzed the prevalence of interatrial block (IAB), its association with frailty and other geriatric syndromes and its association with the incidence of atrial fibrillation (AF) at one year in consecutive elderly patients with myocardial infarction. We included 254 patients. Among patients in sinus rhythm, 149 presented a normal interatrial conduction (67.7%), 37 partial IAB (16.8%) and 34 advanced IAB (15.5%). There was a significant linear association between the degree of IAB and the prevalence of hypertension, previous stroke and mitral regurgitation. A non-significant linear trend was observed between the prevalence of frailty and the degree of IAB, without association with the rest of geriatric syndromes. A non-significant trend towards a higher incidence of AF or mortality in patients with advanced BIA in sinus rhythm (hazard ratio 1.51, 95% confidence interval 0.85-2.70, p = 0.164). Conclusions: a) Patients with symptomatic severe AS managed conservatively are a heterogeneous group. The patients rejected because of advanced age had lower comobidity and surgical risk, as well as a better clinical outcomes. b) Nonagenarians with severe AS are managed conservatively in almost 85% of cases. Despite the strong association between the degree of comorbidity and prognosis, clinical management was not different according to the degree of comorbidity. c) About one third of elderly patients with myocardial infarction presented BIA on the ECG. The data support the hypothesis that BIA is a pre-AF state. A non-significant linear trend was observed between the prevalence of frailty and the degree of IAB. Advanced BIA was associated with a trend towards a higher incidence of AF or death at one year

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

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

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 &lt; 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 &lt; 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