ECLIM-SEHOP: how to develop a platform to conduct academic trials for childhood cancer.

INTRODUCTION: ECLIM-SEHOP platform was created in 2017. Its main objective is to establish the infrastructure to allow Spanish participation into international academic collaborative clinical trials, observational studies, and registries in pediatric oncology. The aim of this manuscript is to describe the activity conducted by ECLIM-SEHOP since its creation. METHODS: The platform's database was queried to provide an overview of the studies integrally and partially supported by the organization. Data on trial recruitment and set-up/conduct metrics since its creation until November 2023 were extracted. RESULTS: ECLIM-SEHOP has supported 47 studies: 29 clinical trials and 18 observational studies/registries that have recruited a total of 5250 patients. Integral support has been given to 25 studies: 16 trials recruiting 584 patients and nine observational studies/registries recruiting 278 patients. The trials include front-line studies for leukemia, lymphoma, brain and solid extracranial tumors, and other key transversal topics such as off-label use of targeted therapies and survivorship. The mean time from regulatory authority submission to first patient recruited was 12.2 months and from first international site open to first Spanish site open was 31.3 months. DISCUSSION: ECLIM-SEHOP platform has remarkably improved the availability and accessibility of international academic clinical trials and has facilitated the centralization of resources in childhood cancer treatment. Despite the progressive improvement on clinical trial set-up metrics, timings should still be improved. The program has contributed to leveling survival rates in Spain with those of other European countries that presented major differences in the past.

Effects of the toxic dinoflagellate Protoceratium reticulatum and its yessotoxins on the survival and feed ingestion of Argopecten purpuratus veliger larvae.

The effects of yessotoxins (YTXs) produced by the dinoflagellate Protoceratium reticulatum in the early stages of bivalves have not been studied in detail. The present study evaluates the effects of P. reticulatum and YTXs on the survival and feed ingestion of veliger larvae of Argopecten purpuratus. Larvae were 96 h-exposed to 500, 1000 and 2000 P. reticulatum cells mL-1, and their equivalent YTX extract was prepared in methanol. Results show a survival mean of 82 % at the highest density of dinoflagellate, and 38 % for larvae with the highest amount of YTX extract. Feed ingestion is reduced in the dinoflagellate exposure treatments as a function of cell density. Therefore, the effect of YTXs on A. purpuratus represents a new and important area of study for investigations into the deleterious effects of these toxins in the early stages of the life cycle of this and, potentially, other bivalves.

Farmed shrimp aquaculture in coastal wetlands of Latin America - A review of environmental issues.

The world production of farmed Whiteleg shrimp was 5,812,180 t in 2020. Ecuador, Mexico, and Brazil produced 1,012,830 in that year according to data FishStatJ. Environmental impact studies were scarce given the rapid growth of this activity, mainly on cummulative impacts, loss of ecosystems services or resilience of wetlands and mangroves. Aspects of the management of environmental impacts published on American studies during 1986-2020 are analyzed. The main impacts included the loss of mangroves and their transformation of these ecosystems and their water bodies by receiving enriched effluents from shrimp farms. Different management measures are discussed between Ecuador, which contributes 63.76 % of American production of white leg shrimp; Brazil which published 46.2 % of the environmental studies of the analyzed period, and Mexico, in an intermediate situation. Finally, alternatives are discussed to improve the management of shrimp aquaculture with emphasis on the Ecuadorian context.

Clinical and molecular characteristics of pediatric low-grade glioma complicated with ventriculo-peritoneal shunt related ascites.

INTRODUCTION: Ventriculo-peritoneal shunt (VPS) related ascites is a rare complication of pediatric low grade gliomas (pLGG). Physiopathology of this complication is not fully understood and there is paucity of data regarding the molecular profile of pLGG gliomas complicating with ascites and the optimal management of this unusual event. METHODS: International multi-institutional retrospective analysis of patients diagnosed with BRAF altered pLGG and ascites arising as a complication of VPS. Demographics, tumor characteristics, therapeutic approaches and outcomes were recorded. RESULTS: Nineteen patients were identified. Median age at diagnosis was 14 months (R: 2-144). Most patients (17; 89.4%) presented with lesions involving the optic pathway. Mean tumor standard volume was 34.8 cm2 (R: 12.5-85.4). Pilocytic Astrocytoma was the most frequent histological diagnosis (14;7 3.7%). Eight (42.1%) tumors harbored BRAF V600-E mutation and seven (36.8%) KIAA1549 fusion. The onset of ascites was documented at a median time of 5 months following VPS insertion. Four (21%) patients were managed with paracentesis only, 7(36.8%) required both paracentesis and shunt diversion, 7(36.8%) required only a shunt diversion and 1 (5.2%) patient was managed conservatively. Chemotherapy regimen was changed in 10 patients following ascites. Eight patients received targeted therapy (4 dabrafenib/4 trametinib) and 5 were radiated. There were eleven survivors with a median OS of 69 months (R: 3-144). CONCLUSIONS: Ascites is an early feature in the clinical course of young patients with midline BRAF altered pLGG, with high mortality rate observed in our cohort. The hypothesis of ascites as an adverse prognostic factor in pLGG warrants further prospective research.

Trophic structure of benthic communities in a Chilean fjord (45°S) influenced by salmon aquaculture: Insights from stable isotopic signatures.

Benthic marine food webs, which recycle organic matter and sustain unique biodiversity, are an important component of estuarine Patagonian fjords; however, these may be heavily influenced by salmon farming activities. Under the above conditions, this study collected several food sources (sediment organic matter, suspended particulate organic matter, macroalgae) and 26 benthic invertebrate species, and analyzed them using a Bayesian mixing model. Briefly, carbon and nitrogen stable isotopes analyses revealed that the highly variable isotopic niche widths respond to food supplies from marine and terrestrial organic matter. In addition, particulate and dissolved waste from salmon farming activities were found to modify isotopic composition ratios in many suspension feeders. Particularly, our results indicate high δ15N values in the sponge Cliona chilensis and the encrusting coral Incrustatus comauensis, which appear to be potential ecological indicators for evaluating stoichiometry imbalances and trace organic pollution sources in fjord environments.

The importance of a functional approach on benthic communities for aquaculture environmental assessment: Trophic groups - A polychaete view.

Polychaetes were studied to assess the effect of aquaculture activity on the seafloor. Very high biodiversity of species was recorded associated with aquaculture centres with Cirratulidae, Spionidae and Paraonidae families being the most diverse and abundant families. The spatial distribution of polychaete trophic groups was the best descriptor for detecting changes on the benthos. Surface and subsurface deposit-feeding species dominated the sites closest to the rafts cages, highlighting Capitella capitata and Cirratulus cirratus as opportunistic species. While replacement and species succession were observed with increasing presence of carnivores and omnivores in sites further away from the salmon cages and experiencing less impact. Analyses based on the distance of feeding modes and ecological groups from the disturbance source were better indicators of the impact that the traditional community approach or sediment biogeochemistry. Therefore, functional traits studies should always be considered on environmental assessments of benthic systems impacted by aquaculture.

Age and DNA methylation subgroup as potential independent risk factors for treatment stratification in children with atypical teratoid/rhabdoid tumors.

BACKGROUND: Controversy exists as to what may be defined as standard of care (including markers for stratification) for patients with atypical teratoid/rhabdoid tumors (ATRTs). The European Rhabdoid Registry (EU-RHAB) recruits uniformly treated patients and offers standardized genetic and DNA methylation analyses. METHODS: Clinical, genetic, and treatment data of 143 patients from 13 European countries were analyzed (2009-2017). Therapy consisted of surgery, anthracycline-based induction, and either radiotherapy or high dose chemotherapy following a consensus among European experts. Fluorescence in situ hybridization, multiplex ligation-dependent probe amplification, and sequencing were employed for assessment of somatic and germline mutations in SWItch/sucrose nonfermentable related, matrix associated, actin dependent regulator of chromatin, subfamily B (SMARCB1). Molecular subgroups (ATRT-SHH, ATRT-TYR, and ATRT-MYC) were determined using DNA methylation arrays, resulting in profiles of 84 tumors. RESULTS: Median age at diagnosis of 67 girls and 76 boys was 29.5 months. Five-year overall survival (OS) and event-free survival (EFS) were 34.7 ±â€…4.5% and 30.5 ±â€…4.2%, respectively. Tumors displayed allelic partial/whole gene deletions (66%; 122/186 alleles) or single nucleotide variants (34%; 64/186 alleles) of SMARCB1. Germline mutations were detected in 26% of ATRTs (30/117). The patient cohort consisted of 47% ATRT-SHH (39/84), 33% ATRT-TYR (28/84), and 20% ATRT-MYC (17/84). Age <1 year, non-TYR signature (ATRT-SHH or -MYC), metastatic or synchronous tumors, germline mutation, incomplete remission, and omission of radiotherapy were negative prognostic factors in univariate analyses (P < 0.05). An adjusted multivariate model identified age <1 year and a non-TYR signature as independent negative predictors of OS: high risk (<1 y + non-TYR; 5-y OS = 0%), intermediate risk (<1 y + ATRT-TYR or ≥1 y + non-TYR; 5-y OS = 32.5 ±â€…8.7%), and standard risk (≥1 y + ATRT-TYR, 5-y OS = 71.5 ±â€…12.2%). CONCLUSIONS: Age and molecular subgroup status are independent risk factors for survival in children with ATRT. Our model warrants validation within future clinical trials.

Evaluation of water quality and heavy metal concentrations in the RAMSAR Wetland El Yali (Central Chile, 33°45'S).

The EYNR is the most important wetland in central Chile because it is protected as a RAMSAR site. It includes coastal lagoons, estuaries and saltmarshes, sustaining an important biodiversity. The chemical complexity was described using water and soil samples, which are characterized by high levels of alkalinity and soil cations. In addition, high concentrations of Cu (0.01-0.080 mg L-1) and Pb (0.120-0.566 mg L-1) in water were measured. Using a simplified index of water quality for oxygen demand, the ecological status of the wetland was classified as bad quality due to the existing use of land. Multivariable analyses and heavy metal index classified this wetland as having low to intermediate deterioration due to the combination of heavy metals. If this trend is allowed to continue unabated, the food web complexes in this wetland are likely to be at the highest risk of induced heavy metal contamination.

Stable isotopes and geochemical indicators in marine sediments as proxies for anthropogenic impact: A baseline for coastal environments of central Chile (33°S).

Stable isotopes and geochemical proxies (TOC/TN and Chla/TOC) in sediments can be used to distinguish organic matter sources (anthropogenic, terrestrial, or marine). This study aims to characterize organic matter (OM) in superficial sediments from three sectors of central Chile (33°S) that are highly influenced by urban and industrial development. Our results show that a substantial fraction of these OM in Quintero Bay is anthropogenic, from industrial and domestic wastewater sources. In contrast, a mixture of terrestrial and anthropogenic OM dominates the isotopic signal of surface sediments from Concón, derived from non-point industrial and agriculture sources associated with the Aconcagua River basin, while Ritoque exhibited a mixture of different OM sources. However, deposition of allochthonous OM in our study area depends on coastal topography, which influences the local currents and well-ventilated waters, promoting the dispersion and assimilation of OM and thus providing an environment with a high capacity for natural remediation.

Management and outcome of children and adolescents with non-medulloblastoma CNS embryonal tumors in Spain: room for improvement in standards of care.

Non-medulloblastoma CNS embryonal tumors (former PNET/Pineoblastomas) are aggressive malignancies with poor outcome that have been historically treated with medulloblastoma protocols. The purpose of this study is to present a tumor-specific, real-world data cohort of patients with CNS-PNET/PB to analyze quality indicators that can be implemented to improve the outcome of these patients. Patients 0-21 years with CNS-PNET treated in eight large institutions were included. Baseline characteristics, treatment and outcome [progression-free and overall survival (PFS and OS respectively)] were analyzed. From 2005 to 2014, 43 patients fulfilled entry criteria. Median age at diagnosis was 3.6 years (range 0.0-14.7). Histology was pineoblastoma (9%), ependymoblastoma (5%), ETANTR (7%) and PNET (77%). Median duration of the main symptom was 2 weeks (range 0-12). At diagnosis, 28% presented with metastatic disease. Seventeen different protocols were used on frontline treatment; 44% had gross total resection, 42% craniospinal radiotherapy, 86% chemotherapy, and 33% autologous hematopoietic stem cell transplantation (aHSCT). Median follow-up for survivors was 3.5 years (range 1.7-9.3). 3-year PFS was 31.9% (95% CI 17-47%) and OS 35.1% (95% CI 20-50%). Age, extent of resection and radiotherapy were prognostic of PFS and OS in univariate analysis (p < 0.05). Our series shows a dismal outcome for CNS-PNET, especially when compared to patients included in clinical trials. Establishing a common national strategy, implementing referral circuits and collaboration networks, and incorporating new molecular knowledge into routine clinical practice are accessible measures that can improve the outcome of these patients.

Improved 6-year overall survival in AT/RT - results of the registry study Rhabdoid 2007.

Atypical teratoid rhabdoid tumors (AT/RT) are characterized by mutations and subsequent inactivation of SMARCB1 (INI1, hSNF5), a predilection for very young children and an unfavorable outcome. The European Registry for rhabdoid tumors (EU-RHAB) was established to generate a common European database and to establish a standardized treatment regimen as the basis for phase I/II trials. Thus, genetic analyses, neuropathologic and radiologic diagnoses, and a consensus treatment regimen were prospectively evaluated. From 2005 to 2009, 31 patients with AT/RT from four countries were recruited into the registry study Rhabdoid 2007 and treated with systemic and intraventricular chemotherapy. Eight patients received high-dose chemotherapy, 23 radiotherapy, and 17 maintenance therapy. Reference evaluations were performed in 64% (genetic analyses, FISH, MLPA, sequencing) up to 97% (neuropathology, INI1 stain). Germ-line mutations (GLM) were detected in 6/21 patients. Prolonged overall survival was associated with age above 3 years, radiotherapy and achievement of a complete remission. 6-year overall and event-free survival rates were 46% (±0.10) and 45% (±0.09), respectively. Serious adverse events and one treatment-related death due to insufficiency of a ventriculo peritoneal shunt (VP-shunt) and consecutive herniation were noted. Acquisition of standardized data including reference diagnosis and a standard treatment schedule improved data quality along with a survival benefit. Treatment was feasible with significant but manageable toxicity. Although our analysis is biased due to heterogeneous adherence to therapy, EU-RHAB provides the best available basis for phase I/II clinical trials.

Development and stability study of glibenclamide oral liquid paediatric formulations for the treatment of permanent neonatal diabetes mellitus.

BACKGROUND: Glibenclamide is a second-generation oral sulfonylurea used to treat neonatal permanent diabetes mellitus. It is more effective and safer than the first-generation agents. However, no liquid oral formulation is commercially available and, therefore, it cannot be used for individuals who cannot swallow the solid form. OBJECTIVES: To develop and study the physicochemical and microbiological stability of two liquid glibenclamide formulations for the treatment of permanent neonatal diabetes mellitus: two suspensions (2.5 mg/mL)-one using glibenclamide raw material and the other, glibenclamide tablets. Furthermore, high-performance liquid chromatography (HPLC) stability showed that the method is optimised and validated for analysis of glibenclamide in the formulations studied. METHODS: Samples were stored at 4°C, 25°C and 40°C. The amount of glibenclamide in each formulation was analysed in duplicate using HPLC at 0, 7, 14, 28, 60 and 90 days. Other parameters were also determined-for example, the appearance, pH and morphology. Microbiological studies according to the guidelines of the US Pharmacopoeia for non-sterile products at 0 and 90 days were carried out. RESULTS: All formulations remained physicochemically and microbiologically stable at three different temperatures during the 90-day study. Therefore, glibenclamide formulations can be stored for at least 90 days at ≤40°C. CONCLUSIONS: These formulations are ideally suited for paediatric patients who usually cannot swallow tablets. The proposed analytical method was suitable for studying the stability of different formulations.

Classification of the ecological quality of the Aysen and Baker Fjords (Patagonia, Chile) using biotic indices.

The AZTI's marine biotic index (AMBI), an ecological indicator for managing estuarine and coastal waters worldwide, was tested in two fjords in Chilean Patagonia. The Aysen Fjord (42° Lat. S) supports intensive salmon farming in coastal ecosystems, while the Baker Fjord (48° Lat. S) is currently just beyond the limit of the southern expansion of salmon concessions. The ecological status of the Aysen Fjord was classified as good, while the status of the Baker Fjord was classified as high and unbalanced. These differences were consistent with our expectations, illustrating the effect of local environmental conditions and human activities, combined with river inputs into semi-confined fjords. This method is appropriate for the evaluation of the ecological status of the fjords, but requires a sufficient amount of data for the robust environmental assessment as proposed by the Water Framework Directive (WFD).

Adenopatías mediastínicas y masa pulmonar cavitada como forma de presentación de la enfermedad de Hodgkin / Mediastinal adenopathies and pulmonary cavitated mass as onset form of Hodgkin's disease

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