A Scoping Review of Focused Ultrasound Enhanced Drug Delivery for Across the Blood-Brain Barrier for Brain Tumors.

BACKGROUND AND OBJECTIVES: Previous mechanisms of opening the blood-brain barrier (BBB) created a hypertonic environment. Focused ultrasound (FUS) has recently been introduced as a means of controlled BBB opening. Here, we performed a scoping review to assess the advances in drug delivery across the BBB for treatment of brain tumors to identify advances and literature gaps. METHODS: A review of current literature was conducted through a MEDLINE search inclusive of articles on FUS, BBB, and brain tumor barrier, including human, modeling, and animal studies written in English. Using the Rayyan platform, 2 reviewers (J.P and C.Y) identified 967 publications. 224 were chosen to review after a title screen. Ultimately 98 were reviewed. The scoping review was designed to address the following questions: (1) What FUS technology improvements have been made to augment drug delivery for brain tumors? (2) What drug delivery improvements have occurred to ensure better uptake in the target tissue for brain tumors? RESULTS: Microbubbles (MB) with FUS are used for BBB opening (BBBO) through cavitation to increase its permeability. Drug delivery into the central nervous system can be combined with MB to enhance transport of therapeutic agents to target brain tissue resulting in suppression of tumor growth and prolonging survival rate, as well as reducing systemic toxicity and degradation rate. There is accumulating evidence demonstrating that drug delivery through BBBO with FUS-MB improves drug concentrations and provides a better impact on tumor growth and survival rates, compared with drug-only treatments. CONCLUSION: Here, we review the role of FUS in BBBO. Identified gaps in the literature include impact of tumor microenvironment and extracellular space, improved understanding and control of MB and drug delivery, further work on ideal pharmacologics for delivery, and clinical use.

Aerobiological and clinical study in the semidesertic area of the Southeastern of Spain.

Aerobiological studies constitute a relevant tool to predict the most influential parameters over the pollen seasons with significant clinical relevance in the allergic populations. The aim of this study was to describe the aerobiological behaviour of the most relevant allergenic sources in the semi-arid area of southeast of Spain (Almería) and to investigate the correlation with meteorological factors and clinical symptoms of allergic patients. Daily pollen count and meteorological parameters of Almería, Spain, were compiled for ten years. The clinical symptoms of 248 allergic patients were also recorded. Descriptive statistics and correlations between variables were assessed. Multivariate analyses were performed to predict the influence of meteorological factors on pollen concentration and the risk of suffer respiratory symptoms. Eight pollen families were identified as the most relevant allergenic sources. Temperature correlated with main pollen season evolution of all taxa whereas rainfall and relative humidity only correlated in Oleaceae, Pinaceae, Amaranthaceae, Asteraceae and Urticaceae. Rainfall and relative humidity were the most influential predictors of pollen concentration, except in Amaranthaceaea and Poaceae families, while temperature only influenced on Cupressaceae and Urticaceae pollen concentrations. A significant positive influence was observed between maximum temperature and rainfall with the appearance of allergic symptoms in patients sensitized to grasses, Parietaria sp. and Olea sp. This study, highlight the main aerobiological features in the region and establish a suitable tool for clinical follow-up and management of allergic patients. Further studies are needed to establish an accurate measurement aimed to control and prevent pollinosis in sensitized patients.

Questions and answers in the management of children with medulloblastoma over the time. How did we get here? A systematic review.

Introduction: Treatment of children with medulloblastoma (MB) includes surgery, radiation therapy (RT) and chemotherapy (CT). Several treatment protocols and clinical trials have been developed over the time to maximize survival and minimize side effects. Methods: We performed a systematic literature search in May 2023 using PubMed. We selected all clinical trials articles and multicenter studies focusing on MB. We excluded studies focusing exclusively on infants, adults, supratentorial PNETs or refractory/relapsed tumors, studies involving different tumors or different types of PNETs without differentiating survival, studies including <10 cases of MB, solely retrospective studies and those without reference to outcome and/or side effects after a defined treatment. Results: 1. The main poor-prognosis factors are: metastatic disease, anaplasia, MYC amplification, age younger than 36 months and some molecular subgroups. The postoperative residual tumor size is controversial.2. MB is a collection of diseases.3. MB is a curable disease at diagnosis, but survival is scarce upon relapse.4. Children should be treated by experienced neurosurgeons and in advanced centers.5. RT is an essential treatment for MB. It should be administered craniospinal, early and without interruptions.6. Craniospinal RT dose could be lowered in some low-risk patients, but these reductions should be done with caution to avoid relapses.7. Irradiation of the tumor area instead of the entire posterior fossa is safe enough.8. Hyperfractionated RT is not superior to conventional RT9. Both photon and proton RT are effective.10. CT increases survival, especially in high-risk patients.11. There are multiple drugs effective in MB. The combination of different drugs is appropriate management.12. CT should be administered after RT.13. The specific benefit of concomitant CT to RT is unknown.14. Intensified CT with stem cell rescue has no benefit compared to standard CT regimens.15. The efficacy of intraventricular/intrathecal CT is controversial.16. We should start to think about incorporating targeted therapies in front-line treatment.17. Survivors of MB still have significant side effects. Conclusion: Survival rates of MB improved greatly from 1940-1970, but since then the improvement has been smaller. We should consider introducing targeted therapy as front-line therapy.

Validación de los datos antropométricos declarados por padres de participantes en el proyecto SENDO / Validation of the anthropometric data reported by parents of participants in the SENDO project

Objetivo: analizar la validez de las medidas antropométricas declaradas por los padres de los participantes en el proyecto SENDO. Método: el proyecto SENDO (SEguimiento del Niño para un Desarrollo Óptimo) es una cohorte pediátrica abierta y prospectiva. Los participantes se reclutan cuando tienen entre 4 y 6 años, y se siguen anualmente mediante un cuestionario “online”. En una submuestra de 82 participantes, se comparó la información antropométrica declarada en el cuestionario basal con las mediciones directas recogidas por el personal investigador. Para ello, se calcularon el índice de correlación intraclase (ICC) y el coeficiente de mala clasificación de Bland-Altman. Resultados: el ICC fue de 0,96 (intervalo de confianza [IC] del 95 %: 0,94-0,98) para el peso; de 0,95 (IC 95 %: 0,92-0,96) para la altura; de 0,75 (IC 95 %: 0,64-0,86) para el perímetro de la cintura, y de 0,84 (IC 95 %: 0,76-0,89) para el perímetro de la cadera. En relación a los índices calculados a partir de esas mediciones, se encontró un ICC de 0,84 (IC 95 %: 0,77-0,90) para el índice de masa corporal; de 0,46 (IC 95 %: 0,27-0,62) para el cociente cintura-cadera, y de 0,59 (IC 95 %: 0,43-0,72) para el índice cintura-altura. El índice de mala clasificación de Bland-Altman osciló entre el 3,7 % para el peso y el 8,5 % para el índice de masa corporal. Conclusiones: se encontró una muy elevada concordancia para la información antropométrica declarada por los padres y la medida de forma directa. Los resultados indican que las medidas antropométricas referidas por los padres, especialmente aquellas con los que están más familiarizados, son válidas y pueden utilizarse en la investigación epidemiológica. (AU)

Objective: to analyze the validity of self-reported somatometry data through a self-reported online questionnaire. Method: the SENDO project (Follow-up of Children for Optimal Development) is a prospective, dynamic pediatric cohort. Participants are recruited when they are between 4 and 6 years old, and followed annually through an online questionnaire. In a subsample of 82 participants, we compared the anthropometric information reported in the baseline questionnaire with the direct measurements collected by the investigating staff. To do this, we calculated the intraclass correlation index (ICC) and the Bland-Altman coefficient. Results: the ICC was 0.96 (95 % confidence interval [CI]: 0.94-0.98 for weight; 0.95 (95 % CI: 0.92-0.96) for height; 0.75 (95 % CI: 0.64-0.86) for waist circumference; and 0.84 (95 % CI: 0.76-0.89) for hip circumference. In relation to the indices calculated from these measurements, we found an ICC of 0.84 (95 % CI: 0.77-0.90) for body mass index; 0.46 (95 % CI: 0.27-0.62) for waist-hip ratio; and 0.59 (95 % CI: 0.43-0.72) for waist-height index. The Bland-Altman index ranged from 3.7 % for weight to 8.5 % for body mass index. Conclusions: we found a high correlation and concordance between the data collected in the physical exam and those reported by the parents. Our results indicate that the anthropometric measures provided by parents, especially those with which they are most familiar, are valid and can be used in epidemiological research. (AU)

[Validation of the anthropometric data reported by parents of participants in the SENDO project]. / Validación de los datos antropométricos declarados por padres de participantes en el proyecto SENDO.

INTRODUCTION: Objective: to analyze the validity of self-reported somatometry data through a self-reported online questionnaire. Method: the SENDO project (Follow-up of Children for Optimal Development) is a prospective, dynamic pediatric cohort. Participants are recruited when they are between 4 and 6 years old, and followed annually through an online questionnaire. In a subsample of 82 participants, we compared the anthropometric information reported in the baseline questionnaire with the direct measurements collected by the investigating staff. To do this, we calculated the intraclass correlation index (ICC) and the Bland-Altman coefficient. Results: the ICC was 0.96 (95 % confidence interval [CI]: 0.94-0.98 for weight; 0.95 (95 % CI: 0.92-0.96) for height; 0.75 (95 % CI: 0.64-0.86) for waist circumference; and 0.84 (95 % CI: 0.76-0.89) for hip circumference. In relation to the indices calculated from these measurements, we found an ICC of 0.84 (95 % CI: 0.77-0.90) for body mass index; 0.46 (95 % CI: 0.27-0.62) for waist-hip ratio; and 0.59 (95 % CI: 0.43-0.72) for waist-height index. The Bland-Altman index ranged from 3.7 % for weight to 8.5 % for body mass index. Conclusions: we found a high correlation and concordance between the data collected in the physical exam and those reported by the parents. Our results indicate that the anthropometric measures provided by parents, especially those with which they are most familiar, are valid and can be used in epidemiological research.

INTRODUCCIÓN: Objetivo: analizar la validez de las medidas antropométricas declaradas por los padres de los participantes en el proyecto SENDO. Método: el proyecto SENDO (Seguimiento del Niño para un Desarrollo Óptimo) es una cohorte pediátrica abierta y prospectiva. Los participantes se reclutan cuando tienen entre 4 y 6 años, y se siguen anualmente mediante un cuestionario "online". En una submuestra de 82 participantes, se comparó la información antropométrica declarada en el cuestionario basal con las mediciones directas recogidas por el personal investigador. Para ello, se calcularon el índice de correlación intraclase (ICC) y el coeficiente de mala clasificación de Bland-Altman. Resultados: el ICC fue de 0,96 (intervalo de confianza [IC] del 95 %: 0,94-0,98) para el peso; de 0,95 (IC 95 %: 0,92-0,96) para la altura; de 0,75 (IC 95 %: 0,64-0,86) para el perímetro de la cintura, y de 0,84 (IC 95 %: 0,76-0,89) para el perímetro de la cadera. En relación a los índices calculados a partir de esas mediciones, se encontró un ICC de 0,84 (IC 95 %: 0,77-0,90) para el índice de masa corporal; de 0,46 (IC 95 %: 0,27-0,62) para el cociente cintura-cadera, y de 0,59 (IC 95 %: 0,43-0,72) para el índice cintura-altura. El índice de mala clasificación de Bland-Altman osciló entre el 3,7 % para el peso y el 8,5 % para el índice de masa corporal. Conclusiones: se encontró una muy elevada concordancia para la información antropométrica declarada por los padres y la medida de forma directa. Los resultados indican que las medidas antropométricas referidas por los padres, especialmente aquellas con los que están más familiarizados, son válidas y pueden utilizarse en la investigación epidemiológica.