Frailty Is Common in Heart Transplant Candidates But Is Not Associated With Clinical Events and Is Reversible After Heart Transplantation.

Assessment of frailty before heart transplant (HT) is recommended but is not standard in most HT protocols. Our objective was to evaluate frailty at inclusion in HT list and during follow-up and to assess the influence of baseline frailty on prognosis. A prospective multicenter study in all adults included in the nonurgent HT waiting list. Frailty was defined as Fried's frailty phenotype score ≥3. Mean follow-up was 25.9 ± 1.2 months. Of 99 patients (mean age 54.8 [43.1 to 62.5] years, 70 men [70.7%]), 28 were frail (28.3%). A total of 85 patients received HT after 0.5 ± 0.01 years. Waiting time was shorter in frail patients (0.6 years [0.3 to 0.8] vs 0.2 years [0.1 to 0.4], p = 0.001) because of an increase in priority. Baseline frailty was not associated with overall mortality, (hazard ratio 0.99 [95% confidence interval 0.41 to 2.37, p = 0.98]). A total of 16 transplant recipients died (18.8%). Of the remaining 69 HT recipients, 65 underwent frailty evaluation during follow-up. Patients without baseline frailty (n = 49) did not develop it after HT. Of 16 patients with baseline frailty, only 2 were still frail at the end of follow-up. Frailty is common in HT candidates but is reversible in most cases after HT and is not associated with post-transplant mortality. Our results suggest that frailty should not be considered an exclusion criterion for HT.

Identification of NRF2 Activation as a Prognostic Biomarker in T-Cell Acute Lymphoblastic Leukaemia.

The standard-of-care treatment of T-cell acute lymphoblastic leukaemia (T-ALL) with chemotherapy usually achieves reasonable rates of initial complete response. However, patients who relapse or do not respond to conventional therapy show dismal outcomes, with cure rates below 10% and limited therapeutic options. To ameliorate the clinical management of these patients, it is urgent to identify biomarkers able to predict their outcomes. In this work, we investigate whether NRF2 activation constitutes a biomarker with prognostic value in T-ALL. Using transcriptomic, genomic, and clinical data, we found that T-ALL patients with high NFE2L2 levels had shorter overall survival. Our results demonstrate that the PI3K-AKT-mTOR pathway is involved in the oncogenic signalling induced by NRF2 in T-ALL. Furthermore, T-ALL patients with high NFE2L2 levels displayed genetic programs of drug resistance that may be provided by NRF2-induced biosynthesis of glutathione. Altogether, our results indicate that high levels of NFE2L2 may be a predictive biomarker of poor treatment response in T-ALL patients, which would explain the poor prognosis associated with these patients. This enhanced understanding of NRF2 biology in T-ALL may allow a more refined stratification of patients and the proposal of targeted therapies, with the ultimate goal of improving the outcome of relapsed/refractory T-ALL patients.

The stigma of mental health professionals towards users with a mental disorder.

Individuals with mental disorders are labeled in such a way that it leads to stigmatization. This generates a disadvantage as regards to the rest of the members of the society, limiting their participation as active members within it and at the same time being deleterious to their way of life. Mental health professionals are not safe from internalizing these stereotypes and prejudices assumed from their environment, thereby showing stigmatizing attitudes and behaviors towards the users in the different mental health resources.

El estigma de los profesionales de salud mental hacia los usuarios con trastorno mental / The stigma of mental health professionals towards users with a mental disorder

Introducción: Las personas con trastornos mentales padecen el etiquetado que provoca el estigma y este a su vez les genera una desventaja con el resto de los componentes de una sociedad, limitando su participación como ciudadanos activos en la misma y mermando su calidad de vida. Los profesionales no están a salvo de interiorizar estos estereotipos y prejuicios asumidos por su entorno reflejándose en sus actitudes y comportamientos hacia los usuarios en los diferentes servicios de salud mental.Metodología: El diseño empleado en este estudio para conocer el estigma de los profesionales de salud mental es un estudio cuantitativo, analizando el nivel de estigma que presentan los profesionales mediante el cuestionario de Atribución-27 (AQ27). La muestra resultó de 59 profesionales.Resultados: Los resultados obtenidos ponen de manifiesto la existencia de actitudes y comportamientos estigmatizadores por parte de los profesionales analizados. Dentro de los datos sociodemográficos de la muestra cabe destacar que el mayor nivel de formación de los profesionales disminuye las actitudes y comportamientos relacionados con el estigma.Conclusiones: Se ha podido constatar la existencia de diferentes factores del estigma como son la ayuda, la coacción, la piedad y la evitación que afectan a los profesionales de la salud mental. (AU)

Introduction: Individuals with mental disorders are labeled in such a way that it leads to stigmatization. This generates a disadvantage as regards to the rest of the members of the society, limiting their participation as active members within it and at the same time being deleterious to their way of life. Mental health professionals are not safe from internalizing these stereotypes and prejudices assumed from their environment, thereby showing stigmatizing attitudes and behaviors towards the users in the different mental health resources.Methodology: The design used in this study to determine the stigma of mental health professionals is a quantitative study, which was used to analyze the level of stigma presented by professionals using the Attribution Questionnaire-27 (AQ27). The sample consisted of 59 professionals.Results: The results obtained showed the existence of stigmatizing attitudes and behaviors by the professionals analyzed. Within the sociodemographic data of the sample, it should be noted that the higher level of education of the professionals decreased the attitudes and behaviors associated to stigma. Conclusions: It was possible to confirm the existence of differentstigma factors such as helping, coercion, pity and avoidancethat affect mental health professionals. (AU)

Lack of Usefulness of Donor-Derived Cell-Free DNA as a Biomarker for Cardiac Allograft Vasculopathy: A Prospective Study.

Background: Cardiac allograft vasculopathy (CAV) remains a major cause of morbidity and mortality among long-term heart transplant recipients. There is an unmet need for a non-invasive biomarker of CAV that could obviate the need to perform surveillance coronary angiograms in these patients. Our aim was to evaluate the performance of Donor-derived Cell Free DNA (dd-cfDNA) as a biomarker of CAV. Methods: We prospectively measured dd-cfDNA levels in all patients undergoing routine coronary angiography >1 year after heart transplant at a single center. Endpoints included the association between dd-cfDNA levels and the presence CAV, according to several prespecified criteria. Results: We included 94 heart transplant recipients, a median of 10.9 years after transplant. Coronary angiogram revealed CAV0, CAV1, CAV2, and CAV3 in 61, 19, 14, and 6% of patients, respectively. Comparison of dd-cfDNA levels in patients with CAV0 and CAV1-2-3 (primary end-point) did not show significant differences (0.92%, IQR 0.46-2.0 vs. 0.46%, IQR 0.075-1.5, p = 0.059), nor did the comparison between patients with stable CAV (no new coronary lesions since previous angiogram, n = 77) and progressive CAV (n = 17); dd-cfDNA values 0.735% (IQR 0.195-2.0) vs. 0.9% (IQR 0.12-1.8), p = 0.76. However, we found an association between NTproBNP levels and CAV degree (p = 0.017). Dd-cfDNA levels did not correlate with NTproBNP (ρ = -0.095). Conclusion: In this study, dd-cfDNA did not perform as a useful biomarker to avoid surveillance coronary angiograms for CAV diagnosis. Clinical Trial Notation: Potential Role of Donor-derived Cell Free DNA as a Biomarker in Cardiac Allograft Vasculopathy, NCT04791852.

Cardiac Transplantation in Danon Disease.

BACKGROUND: Danon disease (DD) is a rare X-linked dominant cardioskeletal myopathy caused by mutations in the lysosome-associated membrane protein-2 (LAMP-2) gene that is usually lethal without cardiac transplantation. The purpose of this study was to characterize post-transplant outcomes in a large cohort of patients with DD who underwent cardiac transplantation. METHODS: The clinical phenotype and outcome data of patients with DD who underwent cardiac transplantation (n = 38; 19 males and 19 females) were obtained from 8 centers. Study outcomes included graft survival, defined as death or retransplantation, and episodes of acute cellular and antibody-mediated rejection and cardiac allograft vasculopathy at 1 year. RESULTS: Median follow-up time after transplantation for the entire cohort was 4.4 years (IQR: 1.5-12.8 years). The median age at transplant for the cohort was 20.2 years (15.8-27.9 years), with no difference in age between sexes. Median pretransplant left-ventricular ejection fraction for the entire cohort was 30% (range 11%-84%). Males had higher pretransplant aspartate aminotransferase, alanine aminotransferase and creatine phosphokinase levels than females (P < 0.001). There were 2 deaths in the entire cohort and 2 retransplants. There was no difference in actuarial graft survival between males and females (P = 0.8965); the estimated graft survival was 87.1% (95%CI: 63.6%-95.9%) at 5 years. One episode (2.7%) of antibody-mediated rejection, grade 2, and 7 episodes (19%) of acute cellular rejection, grade 2 or 3, were reported in patients who survived to discharge (6 females and 1 male; P = 0.172). CONCLUSIONS: Heart transplantation outcomes are acceptable in DD with high probabilities of 5-year graft survival for males and females suggesting that cardiac transplantation is an effective treatment option for DD patients.

Prevalence and characterization of frailty, depression, and cognitive impairment in patients listed for heart transplantation: Results of the FELICITAR prospective registry.

INTRODUCTION: It is recommended to assess frailty prior to heart transplantation (HT). Our objective was to assess the prevalence of frailty in patients listed for HT. METHODS: The FELICITAR registry (Frailty Evaluation after List Inclusion, Characteristics and Influence on TrAnsplantation And Results) is a prospective registry that includes patients listed for HT in three centers, from January 2017 to April 2019. We assessed the presence of frailty, depression, cognitive impairment, and quality of life when included. RESULTS: Ninety-nine patients were included. Of this group, 30.6% were frail, 55 (56.1%) had depression (treated only in nine patients), and 51 (54.8%) had cognitive impairment. Compared with non-frail patients, frail patients were more frequently hospitalized when included in HT waiting list (P = .048), had a lower upper-arm circumference (P = .026), had a lower Barthel index (P = .001), more anemia (P = .010), higher rates of depression (P = .001), poorer quality of life (P = .001), and lower hand-grip strength (P < .001). In multivariate analysis hand-grip strength (odds ratio .91; 95% confidence interval .87-.96, P < .001) and Barthel index (odds ratio .90; 95% confidence interval .82-.99, P = .024) were associated with frailty. CONCLUSIONS: Frailty, depression, and cognitive impairment are common in patients included in HT waiting list. Frailty is strongly associated with hand-grip strength.

Tratamiento exitoso con clozapina en un caso de polidipsia-hiponatremia y discinesia tardía en un paciente con esquizofrenia / Successful treatment with clozapine in a case of polydipsia-hyponatraemia and tardive dyskinesia in a patient with schizophrenia

La polidipsia en el seno de las psicosis crónicas y la hiponatremia subsecuente (también conocido como síndrome PIP: polidipsia, hiponatremia intermitente y psicosis) presentan una prevalencia elevada, probablemente infraestimada, de hasta el 17,5% en pacientes institucionalizados. El tratamiento de la misma con clozapina ha sido propuesto en numerosas ocasiones, siendo además este fármaco considerado de elección en el caso de cuadros de discinesia tardía, entidad secundaria al empleo de fármacos antipsicóticos y que puede llegar a ser tremendamente invalidante para los pacientes, careciendo de tratamiento específico y de difícil manejo terapéutico. Ambos síndromes suponen un prevalente y relevante problema clínico, en el que la ética hace imprescindible evitar el nihilismo terapéutico. Presentamos el caso de un varón de 54 años diagnosticado de esquizofrenia, en el que el cambio de tratamiento a clozapina supuso una importante mejoría en ambos procesos, especialmente en la reducción de la ingesta hídrica, manteniendo estabilidad clínica en el proceso psicopatológico esquizofrénico de base tras el cambio de tratamiento (AU)

Polydipsias within chronic psychosis and subsequent hyponatraemia (also known as PIP syndrome: polydipsia, intermittent hyponatraemia and psychosis) have a high prevalence, probably underestimated, and up to 17.5% in institutionalised patients. The treatment with clozapine has been proposed numerous times, and is also considered the drug of choice in cases of tardive dyskinesia, an entity secondary to the use of antipsychotic drugs, which can be extremely disabling for patients, lacking specific treatment and with a difficult therapeutic management. Both syndromes are prevalent and pose a significant clinical problem, in which ethics are essential to avoid therapeutic nihilism. The case is presented of a 55 year-old male with schizophrenia, in whom the change of treatment to clozapine resulted in a significant improvement in both processes, especially in reducing fluid intake, and maintaining clinical stability of the schizophrenic mental disorder after the intervention (AU)

Adicciones y nuevas tecnologías de la información y de la comunicación: perspectivas de uso para la prevención y el tratamiento

Publicación que recoge las ponencias presentadas en el Seminario Internacional "Aplicación de las nuevas tecnologías a la prevención y asistencia en adicciones", que se desarrolló en el mes de junio de 2008 en Logroño, dentro del marco del proyecto europeo DROJNET.