Valorización de purines mediante pirólisis

En este trabajo se propone el proceso de pirólisis como una posible vía de tratamiento de purines, que permite obtener energía renovable y un sólido, denominado biochar, con propiedades como enmienda orgánica. Se estudia el efecto de la temperatura de pirólisis sobre las propiedades del biochar

Fallo ovárico prematuro en supervivientes a un tumor sólido: puntos clave de manejo

Resumen: Introducción: La insuficiencia ovárica prematura (POI) conlleva importante morbilidad, causando infertilidad, disfunción sexual, disminución de la densidad ósea, riesgo cardiovascular, alteraciones emocionales y mortalidad precoz. Objetivo: Conocer la incidencia y el manejo actual de la POI en supervivientes a un tumor sólido en la infancia y/o adolescencia en nuestro medio. Material y métodos: Estudio observacional multicéntrico. Mujeres entre 12 y 18 años con diagnóstico de tumor sólido y criterios clínicos y/o analíticos de POI. El riesgo se estima según los criterios «The Pediatric Initiative Network of the Oncofertility Consortium». Resultados: Incidencia de 1,5 (30 casos de POI). Edad media 14 ± 2,09. Los tumores sólidos que más se asociaron a la POI fueron: sarcoma de Ewing, tumores cerebrales y germinales. El 83% de los casos no realizó preservación previa al tratamiento. Un 63% no referían menarquia al diagnóstico de la POI. El 97% cumplían criterios de alto riesgo de toxicidad gonadal, a pesar de ello el 47% no realizó ninguna vigilancia previa al diagnóstico. La mediana de tiempo tras el diagnóstico y la aparición del evento es de 43,5 y 29,5 meses tras finalizar tratamiento. Las curvas de Kaplan-Meier, muestran que al 30% de los casos, aparecen en los 2 años tras el diagnóstico y las mujeres con estadio puberal 1 desarrollan insuficiencia más tardíamente que aquellas con estadio 5. Conclusiones: El seguimiento de mujeres en riesgo de la POI, es susceptible de mejora. Las herramientas actuales facilitan conocer el riesgo al planificar los tratamientos del tumor y realizar vigilancia, educación, diagnóstico precoz, preservación e instauración de tratamiento sustitutivo. Todo ello, supondría importantes mejoras en salud. Abstract: Introduction: Primary ovarian insufficiency (POI) carries significant morbidity, causing infertility, sexual disfunction, decreased bone density, cardiovascular risk, emotional distress and early mortality. Objective: To know the incidence and current management of POI in childhood/adolescent solid tumour survivors. Material and methods: We conducted a multicentre observational study. It included female patients aged 12 to 18 years with a diagnosis of solid tumour and meeting clinical or biochemical criteria for POI. The risk was estimated based on the criteria of the Pediatric Initiative Network of the Oncofertility Consortium. Results: We found an incidence of 1.5 (30 cases of POI): The median age at the time of the event was 14 years (standard deviation, 2.09). The solid tumours associated most frequently with POI were Ewing sarcoma and brain and germ cell tumours. Eighty-three percent of patients did not undergo fertility preservation. Sixty-three percent reported not having undergone menarche at the time of ovarian failure. Ninety-seven percent were at high risk of gonadal toxicity, yet 47% were not monitored before the diagnosis. The median time elapsed to the occurrence of the event was 43.5 months after diagnosis and 29.5 months after completing treatment. The Kaplan-Meier curves showed that approximately 30% of POI cases developed within 2 years of diagnosis and that women at Tanner stage 1 developed insufficiency later than women at Tanner stage 5. Conclusions: There is room for improvement in the followup of women at risk of POI in Spain. The tools currently available facilitate risk assessment at the time of treatment planning and allow the implementation of monitoring, education, early diagnosis, fertility preservation, and replacement therapy as needed. All of this would achieve significant improvement in health outcomes

Measurable Residual Disease Assessed by Flow-Cytometry Is a Stable Prognostic Factor for Pediatric T-Cell Acute Lymphoblastic Leukemia in Consecutive SEHOP Protocols Whereas the Impact of Oncogenetics Depends on Treatment.

Robust and applicable risk-stratifying genetic factors at diagnosis in pediatric T-cell acute lymphoblastic leukemia (T-ALL) are still lacking, and most protocols rely on measurable residual disease (MRD) assessment. In our study, we aimed to analyze the impact of NOTCH1, FBXW7, PTEN, and RAS mutations, the measurable residual disease (MRD) levels assessed by flow cytometry (FCM-MRD) and other reported risk factors in a Spanish cohort of pediatric T-ALL patients. We included 199 patients treated with SEHOP and PETHEMA consecutive protocols from 1998 to 2019. We observed a better outcome of patients included in the newest SEHOP-PETHEMA-2013 protocol compared to the previous SHOP-2005 cohort. FCM-MRD significantly predicted outcome in both protocols, but the impact at early and late time points differed between protocols. The impact of FCM-MRD at late time points was more evident in SEHOP-PETHEMA 2013, whereas in SHOP-2005 FCM-MRD was predictive of outcome at early time points. Genetics impact was different in SHOP-2005 and SEHOP-PETHEMA-2013 cohorts: NOTCH1 mutations impacted on overall survival only in the SEHOP-PETHEMA-2013 cohort, whereas homozygous deletions of CDKN2A/B had a significantly higher CIR in SHOP-2005 patients. We applied the clinical classification combining oncogenetics, WBC count and MRD levels at the end of induction as previously reported by the FRALLE group. Using this score, we identified different subgroups of patients with statistically different outcome in both Spanish cohorts. In SHOP-2005, the FRALLE classifier identified a subgroup of high-risk patients with poorer survival. In the newest protocol SEHOP-PETHEMA-2013, a very low-risk group of patients with excellent outcome and no relapses was detected, with borderline significance. Overall, FCM-MRD, WBC count and oncogenetics may refine the risk-stratification, helping to design tailored approaches for pediatric T-ALL patients

Measurable Residual Disease Assessed by Flow-Cytometry Is a Stable Prognostic Factor for Pediatric T-Cell Acute Lymphoblastic Leukemia in Consecutive SEHOP Protocols Whereas the Impact of Oncogenetics Depends on Treatment

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER); Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER).Robust and applicable risk-stratifying genetic factors at diagnosis in pediatric T-cell acute lymphoblastic leukemia (T-ALL) are still lacking, and most protocols rely on measurable residual disease (MRD) assessment. In our study, we aimed to analyze the impact of NOTCH1, FBXW7, PTEN, and RAS mutations, the measurable residual disease (MRD) levels assessed by flow cytometry (FCM-MRD) and other reported risk factors in a Spanish cohort of pediatric T-ALL patients. We included 199 patients treated with SEHOP and PETHEMA consecutive protocols from 1998 to 2019. We observed a better outcome of patients included in the newest SEHOP-PETHEMA-2013 protocol compared to the previous SHOP-2005 cohort. FCM-MRD significantly predicted outcome in both protocols, but the impact at early and late time points differed between protocols. The impact of FCM-MRD at late time points was more evident in SEHOP-PETHEMA 2013, whereas in SHOP-2005 FCM-MRD was predictive of outcome at early time points. Genetics impact was different in SHOP-2005 and SEHOP-PETHEMA-2013 cohorts: NOTCH1 mutations impacted on overall survival only in the SEHOP-PETHEMA-2013 cohort, whereas homozygous deletions of CDKN2A/B had a significantly higher CIR in SHOP-2005 patients. We applied the clinical classification combining oncogenetics, WBC count and MRD levels at the end of induction as previously reported by the FRALLE group. Using this score, we identified different subgroups of patients with statistically different outcome in both Spanish cohorts. In SHOP-2005, the FRALLE classifier identified a subgroup of high-risk patients with poorer survival. In the newest protocol SEHOP-PETHEMA-2013, a very low-risk group of patients with excellent outcome and no relapses was detected, with borderline significance. Overall, FCM-MRD, WBC count and oncogenetics may refine the risk-stratification, helping to design tailored approaches for pediatric T-ALL patients

Origin, functional role, and clinical impact of Fanconi anemia FANCA mutations

Fanconi anemia is characterized by congenital abnormalities, bone marrow failure, and cancer predisposition. To investigate the origin, functional role, and clinical impact of FANCA mutations, we determined a FANCA mutational spectrum with 130 pathogenic alleles. Some of these mutations were further characterized for their distribution in populations, mode of emergence, or functional consequences at cellular and clinical level. The world most frequent FANCA mutation is not the result of a mutational “hot-spot” but results from worldwide dissemination of an ancestral Indo-European mutation. We provide molecular evidence that total absence of FANCA in humans does not reduce embryonic viability, as the observed frequency of mutation carriers in the Gypsy population equals the expected by Hardy-Weinberg equilibrium. We also prove that long distance Alu-Alu recombination can cause Fanconi anemia by originating large interstitial deletions involving FANCA and 2 adjacent genes. Finally, we show that all missense mutations studied lead to an altered FANCA protein that is unable to relocate to the nucleus and activate the FA/BRCA pathway. This may explain the observed lack of correlation between type of FANCA mutation and cellular phenotype or clinical severity in terms of age of onset of hematologic disease or number of malformations