Afrontamiento y malestar emocional parental en relación a la calidad de vida del adolescente oncológico en remisión

Objetivo: Explorar si la calidad de vida (CV) de los adolescentes oncológicos en remisión, está relacionada con el afrontamiento y/o el malestar emocional parental. Método: A partir de un diseño transversal, se recogió información de un total de 62 participantes (31 adolescentes oncológicos en remisión y 31 padres de los anteriores). La CV de los adolescentes fue evaluada a través del Cuestionario de Salud SF-12v2. Para evaluar el estilo de afrontamiento parental se administró el COPE en versión disposicional; y para medir su nivel de malestar emocional actual en relación al cáncer, se administraron dos escalas numéricas de 5 puntos. Los datos médicos y socio-demográficos se obtuvieron a partir de las historias clínicas. Resultados: El estilo de afrontamiento parental de vinculación con el problema (engagement) explicaba un 25% de la varianza del componente mental de CV de los adolescentes oncológicos en remisión (ß = -,500; p = ,004). Conclusiones: La CV del adolescente superviviente a un cáncer, no depende única y exclusivamente de sí mismo. El ámbito familiar en el que éste está inmerso va a tener un papel muy destacado en su adaptación. Por ello es necesario atender las necesidades tanto del paciente, como de sus padres; favoreciendo un mayor ajuste a la situación de remisión, ayudando a disminuir el malestar emocional una vez ha finalizado el tratamiento, y de algún modo, fomentando una mejor y más rápida adaptación a la normalidad de todo el núcleo familiarPurpose: To explore whether Health-Related Quality of Life (HRQoL) in a sample of adolescent survivors of childhood cancer is related to parental coping and/or parental emotional distress. Methods: Sixty-two participants (31 adolescent survivors of childhood cancer and 31 parents) completed several questionnaires in a cross-sectional study. HRQoL was assessed using the SF-12v2 questionnaire. Parental coping styles were assessed using the COPE (dispositional version); and their emotional distress with regard to the oncological experience was assessed by means of two 5-point numeric scales. Medical and demographical data were obtained from medical records. Results: The parental coping style of engagement explained 25% of the variance in mental component dimension of HR-QoL of adolescent survivors of childhood cancer (ß = -,500; p = ,004). Conclusions: HRQoL of adolescent survivors of childhood cancer does not depend only of their own determinants. The family context will play a major role in their adaptation. Therefore it is necessary to take care of the needs of both patients and their parents, encouraging a greater adjustment to the remission phase, helping them to reduce the emotional distress after the end of treatment, and somehow, fostering a better and faster adjustment to the situation of the whole famil

Engineering pH-Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics

Nanovesicles; Neuroblastoma; Pediatric cancerNanovesículas; Neuroblastoma; Cáncer pediátricoNanovesícules; Neuroblastoma; Càncer pediàtricMicroRNAs (miRNAs) are small non-coding endogenous RNAs, which are attracting a growing interest as therapeutic molecules due to their central role in major diseases. However, the transformation of these biomolecules into drugs is limited due to their unstability in the bloodstream, caused by nucleases abundantly present in the blood, and poor capacity to enter cells. The conjugation of miRNAs to nanoparticles (NPs) could be an effective strategy for their clinical delivery. Herein, the engineering of non-liposomal lipid nanovesicles, named quatsomes (QS), for the delivery of miRNAs and other small RNAs into the cytosol of tumor cells, triggering a tumor-suppressive response is reported. The engineered pH-sensitive nanovesicles have controlled structure (unilamellar), size (24 weeks), and are prepared by a green, GMP compliant, and scalable one-step procedure, which are all unavoidable requirements for the arrival to the clinical practice of NP based miRNA therapeutics. Furthermore, QS protect miRNAs from RNAses and when injected intravenously, deliver them into liver, lung, and neuroblastoma xenografts tumors. These stable nanovesicles with tunable pH sensitiveness constitute an attractive platform for the efficient delivery of miRNAs and other small RNAs with therapeutic activity and their exploitation in the clinics.The funding was received by Ministerio de Educación, Cultura y Deporte (Grant no. FPU16/01099), Ministerio de Economía, Industria y Competividad (Grants MAT2016-80820-R, MAT2016-80826-R and SAF2016-75241-R), the Ministry of Science and Innovation (MINECO) of Spain through grant PID2019-105622RB-I00, from Instituto de Salud Carlos III (Grant no. CP16/00006, PI17/00564, PI20/00530, DTS20/00018) (Co-funded by European Regional Development Fund/European Social Fund) “Investing in your future”), from the EuroNanoMed II platform through the NanoVax project, from CIBER-BBN through grant TAG-SMARTLY, Joan Petit Foundation, Asociación Matem Lo Bitxo and Asociación Española Contra el Cáncer (Grant no. LABAE18009SEGU), as well as, Generalitat de Catalunya through the Centres de Recerca de Catalunya (CERCA) programme and grant no. 2017-SGR-918, and from Agency for Management of University and Research Grants (AGAUR) (Grant no 2018LLAV0064 and SIFECAT IU68-010017). Furthermore, ICMAB-CSIC acknowledges support from the MINECO through the Severo Ochoa Programme for Centres of Excellence in R&D (SEV-2015-0496 and CEX2019-000917-S)

Factors associated with the incidence and mortality from COVID-19 in the autonomous communities of Spain

Objetivo Analizar la evolución de la epidemia de COVID-19 después del estado de alarma e identificar factores asociados a las diferencias entre las comunidades autónomas. Método Estudio ecológico que utilizó variables epidemiológicas, demográficas, ambientales y sobre la estructura de los servicios sanitarios como variables explicativas. El periodo de análisis fue desde el 15 de marzo (inicio del estado de alarma) hasta el 22 de abril de 2020. Las tasas de incidencia y de mortalidad fueron las variables respuesta principales. La magnitud de las asociaciones se ha estimado mediante el coeficiente de correlación de Spearman y el análisis de regresión múltiple. Resultados Las tasas de incidencia y de mortalidad en el momento del decreto del estado de alarma se asocian con las tasas de incidencia, mortalidad y demanda hospitalaria actuales. Las temperaturas medias más altas se asocian significativamente con una menor incidencia actual de COVID-19. Asimismo, una mayor proporción de personas mayores en residencias se asocia significativamente a una mortalidad actual más elevada. Conclusión Es posible predecir la evolución de la epidemia a través del análisis de la incidencia y de la mortalidad. Las temperaturas más bajas y la elevada proporción de personas mayores en residencias son factores asociados a un peor pronóstico. Estos parámetros deben ser considerados en las decisiones sobre el momento y la intensidad de la implantación de las medidas de contención. En este sentido, fortalecer la vigilancia epidemiológica es esencial para mejorar las predicciones.Objective Analyze the evolution of the epidemic of COVID-19 after the alarm state and identify factors associated with the differences between the autonomous communities. Method Ecological study that used epidemiological, demographic, environmental and variables on the structure of health services as explanatory variables. The analysis period was from March 15th (the start of the alarm state) until April 22nd, 2020. Incidence and mortality rates were the main response variables. The magnitude of the associations has been estimated using the Spearman correlation coefficient and multiple regression analysis. Results Incidence and mortality rates at the time of decree of alarm status are associated with current incidence, mortality and hospital demand rates. Higher mean temperatures are significantly associated with a lower current incidence of COVID-19 in the autonomous communities. Likewise, a higher proportion of older people in nursing homes is significantly associated with a higher current mortality in the autonomous communities. Conclusion It is possible to predict the evolution of the epidemic through the analysis of incidence and mortality. Lower temperatures and the proportion of older people in residences are factors associated with a worse prognosis. These parameters must be considered in decisions about the timing and intensity of the implementation of containment measures. In this sense, strengthening epidemiological surveillance is essential to improve predictions

The incidence, mortality and timing of Pneumocystis jiroveci pneumonia after hematopoietic cell transplantation: a CIBMTR analysis

Pneumocystis jiroveci pneumonia (PJP) is associated with high morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Little is known about PJP infections after HSCT because of the rarity of disease given routine prophylaxis. We report the results of a CIBMTR study evaluating the incidence, timing, prophylaxis agents, risk factors, and mortality of PJP after autologous (auto) and allogeneic (allo) HSCT. Between 1995 and 2005, 0.63% allo recipients and 0.28% auto recipients of first HSCT developed PJP. Cases occurred as early as 30 days to beyond a year after allo HSCT. A nested case cohort analysis with supplemental data (n=68 allo cases, n=111 allo controls) revealed that risk factors for PJP infection included lymphopenia and mismatch after HSCT. After allo or auto HSCT, overall survival was significantly poorer among cases vs. controls (p=0.0004). After controlling for significant variables, proportional hazards model revealed that PJP cases were 6.87 times more likely to die vs. matched controls (p<0.0001). We conclude PJP infection is rare after HSCT but is associated with high mortality. Factors associated with GVHD and with poor immune reconstitution are among the risk factors for PJP and suggest that protracted prophylaxis for PJP in high-risk HSCT recipients may improve outcomes

Targeting the Hedgehog Pathway in Rhabdomyosarcoma

Embryonic pathways; Paediatric cancer; Soft tissue sarcomasVies embrionàries; Càncer pediàtric; Sarcomes de teixits tousVías embrionarias; Cáncer pediátrico; Sarcomas de tejidos blandosAberrant activation of the Hedgehog (Hh) signalling pathway is known to play an oncogenic role in a wide range of cancers; in the particular case of rhabdomyosarcoma, this pathway has been demonstrated to be an important player for both oncogenesis and cancer progression. In this review, after a brief description of the pathway and the characteristics of its molecular components, we describe, in detail, the main activation mechanisms that have been found in cancer, including ligand-dependent, ligand-independent and non-canonical activation. In this context, the most studied inhibitors, i.e., SMO inhibitors, have shown encouraging results for the treatment of basal cell carcinoma and medulloblastoma, both tumour types often associated with mutations that lead to the activation of the pathway. Conversely, SMO inhibitors have not fulfilled expectations in tumours—among them sarcomas—mostly associated with ligand-dependent Hh pathway activation. Despite the controversy existing regarding the results obtained with SMO inhibitors in these types of tumours, several compounds have been (or are currently being) evaluated in sarcoma patients. Finally, we discuss some of the reasons that could explain why, in some cases, encouraging preclinical data turned into disappointing results in the clinical setting.This article was funded by grants from: Institut Català d’Oncologia (ICO); Instituto de Salud Carlos III (PI18/00398 and FI18/00178); ACCIÓ (COMRDI15-1-0014); Fundació la Marató de TV3; Fundació Albert Bosch; Rotary Clubs Barcelona Eixample, Barcelona Diagonal, Santa Coloma de Gramanet, München-Blutenburg, Deutschland Gemeindienst e.V. and others from Barcelona and province; Fundation Amics Joan Petit; Del Hospital a la cathedral Initiative by Xavi Vallès; and Mi compañero de viaje Association

A risk factor analysis of outcomes after unrelated cord blood transplantation for children with Wiskott-Aldrich syndrome

Wiskott-Aldrich syndrome is a severe X-linked recessive immune deficiency disorder. A scoring system of Wiskott-Aldrich syndrome severity (0.5-5) distinguishes 2 phenotypes: X-linked thrombocytopenia and classic Wiskott-Aldrich syndrome. Hematopoietic cell transplantation is curative for Wiskott-Aldrich syndrome, however the use of unrelated umbilical cord blood transplantation has seldom been described. We analyzed umbilical cord blood transplantation outcomes for 90 patients. Median age at umbilical cord blood transplantation was 1.5 years. Patients were classified according to clinical scores (2 (23%), 3 (30%), 4 (23%) and 5 (19%)). Most patients received HLA mismatched umbilical cord blood transplantation and myeloablative conditioning with anti-thymocyte globulin. Cumulative incidence of neutrophil recovery at day-60 was 89% and day-100 acute graft-versus-host disease grade II-IV was 38%; use of methotrexate for graft-versus- host disease prophylaxis delayed engraftment (p=0.02), but decreased acute graft-versus-host disease (p=0.03). At 5-year, overall survival and event-free survival were 75% and 70%, respectively. Estimated 5 year- event-free survival was 83%, 73% and 55% for patients with clinical score 2, 4-5 and 3, respectively. In multivariate analysis, age<2years at umbilical cord blood transplantation and clinical phenotype X-linked thrombocytopenia were associated with improved event-free survival. Overall survival tended to be improved after 2007 (p=0.09). In conclusion, umbilical cord blood transplantation is a good alternative option for young children with Wiskott-Aldrich syndrome lacking an HLA identical stem cell donor

Integrin alpha9 emerges as a key therapeutic target to reduce metastasis in rhabdomyosarcoma and neuroblastoma

Dissemination; Paediatric cancer; Solid tumoursDiseminación; Cáncer pediátrico; Tumores sólidosDisseminació; Càncer pediàtric; Tumors sòlidsThe majority of current cancer therapies are aimed at reducing tumour growth, but there is lack of viable pharmacological options to reduce the formation of metastasis. This is a paradox, since more than 90% of cancer deaths are attributable to metastatic progression. Integrin alpha9 (ITGA9) has been previously described as playing an essential role in metastasis; however, little is known about the mechanism that links this protein to this process, being one of the less studied integrins. We have now deciphered the importance of ITGA9 in metastasis and provide evidence demonstrating its essentiality for metastatic dissemination in rhabdomyosarcoma and neuroblastoma. However, the most translational advance of this study is to reveal, for the first time, the possibility of reducing metastasis by pharmacological inhibition of ITGA9 with a synthetic peptide simulating a key interaction domain of ADAM proteins, in experimental metastasis models, not only in childhood cancers but also in a breast cancer model.This research was supported by grants from: Institut Català d’Oncologia (ICO); Instituto de Salud Carlos III (PI18/00398 and FI18/00178); ACCIÓ (COMRDI15-1-0014); Fundació la Marató de TV3; Fundació A. BOSCH; Rotary Clubs Barcelona Eixample, Barcelona Diagonal, Santa Coloma de Gramanet, München-Blutenburg, Deutschland Gemeindienst e.V. and others from Barcelona and province; Eric Abidal Foundation; Del Hospital a la catedral Initiative by Xavi Vallès; and Mi compañero de viaje Association

The oral KIF11 inhibitor 4SC-205 exhibits antitumor activity and potentiates standard and targeted therapies in primary and metastatic neuroblastoma models

Inhibidor de KIF11; Terapias dirigidas; MetástasisInhibidor de KIF11; Teràpies dirigides; MetàstasiKIF11 inhibitor; Targeted therapies; MetastasisIn summary, our study provides a rationale for the future therapeutic integration in clinical trials of 4SC-205, an structurally distinct oral KIF11 inhibitor that shows potent antitumor activity in multiple preclinical neuroblastoma models and sensitizes neuroblastoma cells to standard chemotherapy and specific neuroblastoma-targeted therapies.The financial support for this research was provided by Instituto de Salud Calos III (PI20/00530 to Miguel F. Segura; PI20/01107 to Rosa Noguera; PI17/02248 and CPII18/00027 to Anna Santamaria; PI19/01320 to Alberto Villanueva); Ministerio de Educación, Cultura y Deporte (Grant no. FPU16/01099 to Marc Masanas). This work was also supported by the Asociación NEN (Nico contra el cancer infantil 2017–PVR00157)