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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.
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Ensaios Clínicos como Assunto , Neoplasias , Sistema de Registros , Humanos , Criança , Neoplasias/terapia , Espanha , Oncologia , Estudos Observacionais como Assunto , Cooperação Internacional , Seleção de PacientesRESUMO
We use a formulation of Noether's theorem for contact Hamiltonian systems to derive a relation between the thermodynamic entropy and the Noether invariant associated with time-translational symmetry. In the particular case of thermostatted systems at equilibrium, we show that the total entropy of the system plus the reservoir are conserved as a consequence thereof. Our results contribute to understanding thermodynamic entropy from a geometric point of view.
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Group 4 tumours (MBGrp4) represent the majority of non-WNT/non-SHH medulloblastomas. Their clinical course is poorly predicted by current risk-factors. MBGrp4 molecular substructures have been identified (e.g. subgroups/cytogenetics/mutations), however their inter-relationships and potential to improve clinical sub-classification and risk-stratification remain undefined. We comprehensively characterised the paediatric MBGrp4 molecular landscape and determined its utility to improve clinical management. A clinically-annotated discovery cohort (n = 362 MBGrp4) was assembled from UK-CCLG institutions and SIOP-UKCCSG-PNET3, HIT-SIOP-PNET4 and PNET HR + 5 clinical trials. Molecular profiling was undertaken, integrating driver mutations, second-generation non-WNT/non-SHH subgroups (1-8) and whole-chromosome aberrations (WCAs). Survival models were derived for patients ≥ 3 years of age who received contemporary multi-modal therapies (n = 323). We first independently derived and validated a favourable-risk WCA group (WCA-FR) characterised by ≥ 2 features from chromosome 7 gain, 8 loss, and 11 loss. Remaining patients were high-risk (WCA-HR). Subgroups 6 and 7 were enriched for WCA-FR (p < 0·0001) and aneuploidy. Subgroup 8 was defined by predominantly balanced genomes with isolated isochromosome 17q (p < 0·0001). While no mutations were associated with outcome and overall mutational burden was low, WCA-HR harboured recurrent chromatin remodelling mutations (p = 0·007). Integration of methylation and WCA groups improved risk-stratification models and outperformed established prognostication schemes. Our MBGrp4 risk-stratification scheme defines: favourable-risk (non-metastatic disease and (i) subgroup 7 or (ii) WCA-FR (21% of patients, 5-year PFS 97%)), very-high-risk (metastatic disease with WCA-HR (36%, 5-year PFS 49%)) and high-risk (remaining patients; 43%, 5-year PFS 67%). These findings validated in an independent MBGrp4 cohort (n = 668). Importantly, our findings demonstrate that previously established disease-wide risk-features (i.e. LCA histology and MYC(N) amplification) have little prognostic relevance in MBGrp4 disease. Novel validated survival models, integrating clinical features, methylation and WCA groups, improve outcome prediction and re-define risk-status for ~ 80% of MBGrp4. Our MBGrp4 favourable-risk group has MBWNT-like excellent outcomes, thereby doubling the proportion of medulloblastoma patients who could benefit from therapy de-escalation approaches, aimed at reducing treatment induced late-effects while sustaining survival outcomes. Novel approaches are urgently required for the very-high-risk patients.
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Neoplasias Cerebelares , Meduloblastoma , Criança , Humanos , Meduloblastoma/patologia , Fatores de Risco , Mutação/genética , Aberrações Cromossômicas , Neoplasias Cerebelares/patologia , PrognósticoRESUMO
We derive a formula for the dry adiabatic lapse rate of atmospheres composed of real gases. We restrict our study to those described by a family of two-parameter cubic equations of state and the recent Guevara-Rodríguez noncubic equation. Since our formula depends on the adiabatic curves, we compute them all at once, considering molecules that can move, rotate, and vibrate, for any equation of state. To illustrate our results, we estimate the lapse rate of the troposphere of Titan, obtaining a better approximation to the observed data in some instances, when compared to the estimation provided by the virial expansion up to the third order.
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Introducción: La drepanocitosis es una anemia emergente en Europa que condiciona una elevada morbilidad con complicaciones agudas y crónicas. El manejo de estos pacientes es complejo y requiere atención interdisciplinar. El objetivo del estudio es analizar las características y el manejo de los pacientes con drepanocitosis que ingresan por complicaciones agudas.Métodos: Estudio descriptivo retrospectivo de los ingresos por complicaciones agudas de pacientes con drepanocitosis menores de 16 años en un hospital terciario entre 2010 y 2020. Se revisaron los datos clínicos, analíticos y radiológicos.Resultados: Se incluyeron 71 ingresos correspondientes a 25 pacientes, el 40% diagnosticados por cribado neonatal. Los ingresos se incrementaron de forma progresiva durante este periodo. Los diagnósticos más frecuentes fueron la crisis vasooclusiva (35,2%), el síndrome febril (33,8%) y el síndrome torácico agudo (32,3%). Nueve pacientes precisaron ingreso en cuidados intensivos. En 20 ingresos se obtuvo documentación microbiológica, 60% bacterias. En el 86% se administró antibioterapia y 28% precisaron analgesia con opioides. El 89% cumplían la pauta de vacunación adecuada y el 41% recibían hidroxiurea previo al ingreso.Conclusiones: Las complicaciones agudas que precisan ingreso hospitalario son frecuentes en los pacientes con drepanocitosis, siendo las más habituales la crisis vasooclusiva y el síndrome febril. Esto conlleva un uso elevado de antibioterapia y opioides. El diagnóstico precoz facilita el reconocimiento de complicaciones de riesgo vital como el síndrome torácico agudo y el secuestro esplénico. A pesar de las medidas preventivas y los tratamientos indicados en la actualidad, estas complicaciones agudas precisan manejo hospitalario. (AU)
Introduction: Sickle cell disease is an emerging anemia in Europe leading to high morbidity with severe acute complications requiring hospital admission and chronic consequences. The management of these patients is complex and needs interdisciplinary care. The objective is to analyze clinical characteristics and management of patients with sickle cell disease admitted for acute complications.Methods: Retrospective descriptive study of admissions for acute complications of patients with sickle cell disease under 16 years of age in a tertiary hospital between 2010 and 2020. Clinical, laboratory and radiological data were reviewed.Results: We included 71 admissions corresponding to 25 patients, 40% diagnosed by neonatal screening. Admissions increased during this period. The most frequent diagnoses were vaso-occlusive crisis (35.2%), febrile syndrome (33.8%) and acute chest syndrome (32.3%). Nine patients required critical care at PICU. Positive microbiological results were confirmed in 20 cases, bacterial in 60%. Antibiotic therapy was administered in 86% of cases and the vaccination schedule of asplenia was adequately fulfilled by 89%. Opioid analgesia was required in 28%. Chronic therapy with hydroxyurea prior to admission was used in 41%.Conclusions: Acute complications requiring hospital admission are frequent in patients with sickle cell disease, being vaso-occlusive crisis and febrile syndrome the most common. These patients need a high use of antibiotics and opioid analgesia. Prior diagnosis facilitates the recognition of life-threatening complications such as acute chest syndrome and splenic sequestration. Despite the prophylactic and therapeutic measures currently provided to these patients, many patients suffer acute complications that require hospital management. (AU)
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Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Síndrome Torácica Aguda , Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico , Triagem Neonatal , Epidemiologia Descritiva , Estudos RetrospectivosRESUMO
INTRODUCTION: Sickle cell disease is an emerging anemia in Europe leading to high morbidity with severe acute complications requiring hospital admission and chronic consequences. The management of these patients is complex and needs interdisciplinary care. The objective is to analyze clinical characteristics and management of patients with sickle cell disease admitted for acute complications. METHODS: Retrospective descriptive study of admissions for acute complications of patients with sickle cell disease under 16 years of age in a tertiary hospital between 2010 and 2020. Clinical, laboratory and radiological data were reviewed. RESULTS: We included 71 admissions corresponding to 25 patients, 40% diagnosed by neonatal screening. Admissions increased during this period. The most frequent diagnoses were vaso-occlusive crisis (35.2%), febrile syndrome (33.8%) and acute chest syndrome (32.3%). Nine patients required critical care at PICU. Positive microbiological results were confirmed in 20 cases, bacterial in 60%. Antibiotic therapy was administered in 86% of cases and the vaccination schedule of asplenia was adequately fulfilled by 89%. Opioid analgesia was required in 28%. Chronic therapy with hydroxyurea prior to admission was used in 41%. CONCLUSIONS: Acute complications requiring hospital admission are frequent in patients with sickle cell disease, being vaso-occlusive crisis and febrile syndrome the most common. These patients need a high use of antibiotics and opioid analgesia. Prior diagnosis facilitates the recognition of life-threatening complications such as acute chest syndrome and splenic sequestration. Despite the prophylactic and therapeutic measures currently provided to these patients, many patients suffer acute complications that require hospital management.
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Síndrome Torácica Aguda , Anemia Falciforme , Síndrome Torácica Aguda/diagnóstico , Síndrome Torácica Aguda/epidemiologia , Síndrome Torácica Aguda/etiologia , Analgésicos Opioides , Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/terapia , Humanos , Recém-Nascido , Estudos Retrospectivos , Centros de Atenção TerciáriaRESUMO
Medulloblastoma is the primary malignant tumor of the Central Nervous System (CNS) most common in pediatrics. We present here, the histological, molecular, and functional analysis of a cohort of 88 pediatric medulloblastoma tumor samples. The WNT-activated subgroup comprised 10% of our cohort, and all WNT-activated patients had exon 3 CTNNB1 mutations and were immunostained for nuclear ß-catenin. One novel heterozygous CTNNB1 mutation was found, which resulted in the deletion of ß-catenin Ser37 residue (ΔS37). The ΔS37 ß-catenin variant ectopically expressed in U2OS human osteosarcoma cells displayed higher protein expression levels than wild-type ß-catenin, and functional analysis disclosed gain-of-function properties in terms of elevated TCF/LEF transcriptional activity in cells. Our results suggest that the stabilization and nuclear accumulation of ΔS37 ß-catenin contributed to early medulloblastoma tumorigenesis.
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PURPOSE: To summarize the peer-reviewed literature on corneal structural changes after orthokeratology (OK) and to analyze the quality of the studies published. METHODS: An exhaustive search was carried out in the databases Pubmed MEDLINE, Web of Science and Scopus. Original studies in English, with a cohort or experimental design and analyzing the cellular and structural changes of the cornea after OK fitting for myopia correction were selected. The NewCastle-Ottawa Assessment Scale (NOS) tool was used to analyze the quality of the studies selected. RESULTS: The search provided a total of 1837 articles, of which 12 were selected following the inclusion and exclusion criteria. All studies had good quality according to the NOS tool (mean 7.58 ± 1.31). The mean ± standard deviation follow-up period of lens wear in the studies evaluated was 19.27 ± 33.97 months. The following reversible changes after OK have been reported: reduction in central epithelial basal cells, an increase in height and especially in width of superficial epithelial cells, as well as an increase in central stromal thickness and in the number of active keratocytes. Concerning corneal endothelium, only changes in terms of polymegathism were reported that were compatible with those observed for other types of contact lens wear. In relation to corneal sensitivity, there was a reduction during the use of OK, as well as in the nervous density of the sub-basal plexus at the central level, with some contradictory outcomes concerning the reversibility of these changes. CONCLUSION: OK produces reversible structural changes in the central epithelium and central anterior corneal stroma, as well as a decrease in the nerve density of the sub-basal plexus and corneal sensitivity. The quality of published studies evaluating these aspects is good, although more studies are needed to evaluate longer follow-up changes.
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Lentes de Contato , Miopia , Procedimentos Ortoceratológicos , Córnea , Topografia da Córnea , Humanos , Miopia/terapiaRESUMO
BACKGROUND: The disposable bronchoscope is an excellent alternative to face the problem of SARS-CoV-2 and other cross infections, but the bronchoscopist's perception of its quality has not been evaluated. METHODS: To evaluate the quality of the Ambu-aScope4 disposable bronchoscope, we carried out a cross-sectional study in 21 Spanish pulmonology services. We use a standardized questionnaire completed by the bronchoscopists at the end of each bronchoscopy. The variables were described with absolute and relative frequencies, measures of central tendency and dispersion depending on their nature. The existence of learning curves was evaluated by CUSUM analysis. RESULTS: The most frequent indications in 300 included bronchoscopies was bronchial aspiration in 69.3% and the median duration of these was 9.1 min. The route of entry was nasal in 47.2% and oral in 34.1%. The average score for ease of use, image, and aspiration quality was 80/100. All the planned techniques were performed in 94.9% and the bronchoscopist was satisfied in 96.6% of the bronchoscopies. They highlighted the portability and immediacy of the aScope4TM to start the procedure in 99.3%, the possibility of taking and storing images in 99.3%. The CUSUM analysis showed average scores > 70/100 from the first procedure and from the 9th procedure more than 80% of the scores exceeded the 80/100 score. CONCLUSIONS: The aScope4™ scored well for ease of use, imaging, and aspiration. We found a learning curve with excellent scores from the 9th procedure. Bronchoscopists highlighted its portability, immediacy of use and the possibility of taking and storing images.
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Atitude do Pessoal de Saúde , Broncoscópios , Broncoscopia/instrumentação , Equipamentos Descartáveis , Conhecimentos, Atitudes e Prática em Saúde , Pneumologistas , Competência Clínica , Estudos Transversais , Desenho de Equipamento , Pesquisas sobre Atenção à Saúde , Humanos , Curva de Aprendizado , Estudos Prospectivos , EspanhaRESUMO
BACKGROUND: We evaluated an inactivated quadrivalent influenza vaccine (IIV4) in children 6-35 months of age in a phase III, observer-blind trial. METHODS: The aim of this analysis was to estimate vaccine efficacy (VE) in preventing laboratory-confirmed influenza in each of 5 independent seasonal cohorts (2011-2014), as well as vaccine impact on healthcare utilization in 3 study regions (Europe/Mediterranean, Asia-Pacific and Central America). Healthy children were randomized 1:1 to IIV4 or control vaccines. VE was estimated against influenza confirmed by reverse transcription polymerase chain reaction on nasal swabs. Cultured isolates were characterized as antigenically matched/mismatched to vaccine strains. RESULTS: The total vaccinated cohort included 12,018 children (N = 1777, 2526, 1564, 1501 and 4650 in cohorts 1-5, respectively). For reverse transcription polymerase chain reaction confirmed influenza of any severity (all strains combined), VE in cohorts 1-5 was 57.8%, 52.9%, 73.4%, 30.3% and 41.4%, respectively, with the lower limit of the 95% confidence interval >0 for all estimates. The proportion of vaccine match for all strains combined in each cohort was 0.9%, 79.3%, 72.5%, 24.1% and 28.6%, respectively. Antibiotic use associated with influenza illness was reduced with IIV4 by 71% in Europe, 36% in Asia Pacific and 59% in Central America. CONCLUSIONS: IIV4 prevented influenza in children 6-35 months of age in each of 5 separate influenza seasons in diverse geographical regions. A possible interaction between VE, degree of vaccine match and socioeconomic status was observed. The IIV4 attenuated the severity of breakthrough influenza illness and reduced healthcare utilization, particularly antibiotic use.
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Vacinas contra Influenza/imunologia , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Aceitação pelo Paciente de Cuidados de Saúde , Vacinas de Produtos Inativados/imunologia , Feminino , Geografia Médica , Humanos , Vírus da Influenza A/genética , Vírus da Influenza A/imunologia , Vírus da Influenza B/genética , Vírus da Influenza B/imunologia , Vacinas contra Influenza/administração & dosagem , Masculino , Avaliação de Resultados em Cuidados de Saúde , Vigilância em Saúde Pública , Estações do Ano , Vacinas de Produtos Inativados/administração & dosagemRESUMO
Infant gliomas have paradoxical clinical behavior compared to those in children and adults: low-grade tumors have a higher mortality rate, while high-grade tumors have a better outcome. However, we have little understanding of their biology and therefore cannot explain this behavior nor what constitutes optimal clinical management. Here we report a comprehensive genetic analysis of an international cohort of clinically annotated infant gliomas, revealing 3 clinical subgroups. Group 1 tumors arise in the cerebral hemispheres and harbor alterations in the receptor tyrosine kinases ALK, ROS1, NTRK and MET. These are typically single-events and confer an intermediate outcome. Groups 2 and 3 gliomas harbor RAS/MAPK pathway mutations and arise in the hemispheres and midline, respectively. Group 2 tumors have excellent long-term survival, while group 3 tumors progress rapidly and do not respond well to chemoradiation. We conclude that infant gliomas comprise 3 subgroups, justifying the need for specialized therapeutic strategies.
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Neoplasias Encefálicas/genética , Metilação de DNA , Epigenômica/métodos , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Receptores Proteína Tirosina Quinases/genética , Quinase do Linfoma Anaplásico/genética , Quinase do Linfoma Anaplásico/metabolismo , Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/metabolismo , Feminino , Glioma/classificação , Glioma/metabolismo , Humanos , Lactente , Recém-Nascido , Masculino , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Proto-Oncogênicas c-met/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Receptor trkA/genética , Receptor trkA/metabolismo , Análise de Sobrevida , Sequenciamento do Exoma/métodosRESUMO
BACKGROUND: In an exploratory analysis of an inactivated quadrivalent influenza vaccine (IIV4) trial in children 6-35 months without risk factors for influenza, we evaluated clinical presentation of influenza illness and vaccine impact on health outcomes. METHODS: This phase III trial was conducted in 13 geographically diverse countries across 5 influenza seasons (2011-2014). Children were randomized 1:1 to IIV4 or control. Active surveillance was performed for influenza-like episodes (ILE); influenza was confirmed by reverse transcription polymerase chain reaction (RT-PCR). The total vaccinated cohort was evaluated (N = 12,018). RESULTS: 5702 children experienced ≥1 ILE; 356 (IIV4 group) and 693 (control group) children had RT-PCR-confirmed influenza. Prevalence of ILE was similar in RT-PCR-positive and RT-PCR-negative cases regardless of vaccination. Breakthrough influenza illness was attenuated in children vaccinated with IIV4; moderate-to-severe illness was 41% less likely to be reported in the IIV4 group than the control group [crude odds ratio: 0.59 (95% confidence intervals: 0.44-0.77)]. Furthermore, fever >39°C was 46% less frequent following vaccination with IIV4 than with control [crude odds ratio: 0.54 (95% confidence intervals: 0.39-0.75)] in children with breakthrough illness. Health outcome analysis showed that, each year, IIV4 would prevent 54 influenza cases per 1000 children and 19 children would need to be vaccinated to prevent 1 new influenza case. CONCLUSIONS: In addition to preventing influenza in 50% of participants, IIV4 attenuated illness severity and disease burden in children who had a breakthrough influenza episode despite vaccination.
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Vacinas contra Influenza/imunologia , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Pré-Escolar , Feminino , Hospitalização , Humanos , Lactente , Vacinas contra Influenza/administração & dosagem , Influenza Humana/diagnóstico , Masculino , Razão de Chances , Prevalência , Modelos de Riscos Proporcionais , Vigilância em Saúde Pública , Índice de Gravidade de Doença , Avaliação de Sintomas , Vacinação , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologiaRESUMO
BACKGROUND: A quadrivalent split-virion inactivated influenza vaccine (VaxigripTetra™, Sanofi Pasteur; IIV4) containing two A strains (H1N1 and H3N2) and B strains from both lineages (Victoria and Yamagata) was approved in Europe in 2016 for individuals agedâ¯≥â¯3â¯years. This study examined the efficacy and safety of IIV4 in children aged 6-35â¯months. METHODS: This was a phase III randomised controlled trial conducted in Latin America, Asia, Africa, and Europe during the Northern Hemisphere 2014/2015 and 2015/2016 and Southern Hemisphere 2014 and 2015 influenza seasons. Healthy children aged 6-35â¯months not previously vaccinated against influenza were randomised to receive two full doses 28â¯days apart of IIV4, placebo, the licensed trivalent split-virion inactivated vaccine (IIV3), an investigational IIV3 containing a B strain from the alternate lineage. The primary objective was to demonstrate efficacy against influenza illness caused by any strain or vaccine-similar strains. RESULTS: The study enrolled 5806 participants. Efficacy, assessed in 4980 participants completing the study according to protocol, was demonstrated for IIV4. Vaccine efficacy was 50.98% (97% CI, 37.36-61.86%) against influenza caused by any A or B type and 68.40% (97% CI, 47.07-81.92%) against influenza caused by vaccine-like strains. Safety profiles were similar for IIV4, placebo, and the IIV3s, although injection-site reactions were slightly more frequent for IIV4 than placebo. CONCLUSIONS: IIV4 was safe and effective for protecting children aged 6-35â¯months against influenza illness caused by vaccine-similar or any circulating strains. CLINICAL TRIAL REGISTRATION: EudraCT no. 2013-001231-51.
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Anticorpos Antivirais/sangue , Imunogenicidade da Vacina , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , África , América , Ásia , Pré-Escolar , Método Duplo-Cego , Europa (Continente) , Feminino , Humanos , Lactente , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H3N2 , Vírus da Influenza B , Vacinas contra Influenza/efeitos adversos , Internacionalidade , Masculino , Estações do Ano , Vacinas de Produtos Inativados/imunologiaRESUMO
BACKGROUND: Revascularization with carotid stent (CAS) is considered the therapeutic alternative to endarterectomy (CEA). However, its role compared to CEA remains questioned, mainly due of the heterogeneity of long-term results. The objective of this study was to report the efficacy and durability of CAS in terms of stroke prevention in a "real world experience". METHOD: This was a single-center retrospective analysis of 344 patients treated with CAS between January 2001 and December 2015.The primary outcome of the trial was stroke, myocardial infarction, or death during a periprocedural period or any stroke event over a 15-year follow-up. The secondary aim was to identify risk factors for 30-day complications, long-term neurological complications, and intra-stent restenosis. RESULTS: The primary composite end point (any stroke, myocardial infarction, or death during the periprocedural period) was 2.3%. The use of an EPD was protective against major complications.Long-term follow-up was achieved in 294 patients (85,5%) with a median of 50 months (range 0-155 months). Fifty-six (16,3%) died within this period, most commonly of nonvascular causes (4 patients had stroke-related deaths). During the follow-up period, 8 strokes and 3 TIAs were diagnosed (3.2%).ISR determined by sequential ultrasound was assessed in 4.4% of the patients and remained asymptomatic in all but 2 patients (0.6%). All patients with restenosis underwent revascularization with balloon angioplasty. CONCLUSION: The long-term follow-up results of our study validate CAS as a safe and durable procedure with which to prevent ipsilateral stroke, with an acceptable rate of restenosis, recurrence and mortality.
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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.
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Neoplasias Encefálicas/terapia , Pinealoma/terapia , Padrão de Cuidado , Adolescente , Neoplasias Encefálicas/diagnóstico , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Pinealoma/diagnóstico , Espanha , Análise de Sobrevida , Resultado do TratamentoRESUMO
Los tumores pediátricos del sistema nervioso central (SNC) con diseminación leptomeníngea tienen mal pronóstico y es preciso encontrar nuevas alternativas terapéuticas. Una de las principales dificultades en el tratamiento de los tumores del SNC es la penetración de la barrera hematoencefálica, por lo que el tratamiento intratecal ha demostrado su eficacia en múltiples tumores pediátricos. En este artículo se revisa la experiencia disponible sobre la utilización de citarabina liposomal para pacientes pediátricos con tumores del SNC con diseminación leptomeníngea: farmacología, forma de administración, datos de seguridad y estudios de eficacia
Leptomeningeal dissemination in paediatric central nervous system (CNS) tumours is associated with a poor outcome, and new therapeutic strategies are desperately needed. One of the main difficulties in the treatment of CNS tumours is blood brain barrier penetration. Intrathecal therapy has shown to be effective in several paediatric tumours. The aim of this article is to review the data available on the use of liposomal cytarabine for paediatric patients with leptomeningeal dissemination of CNS tumours, including the pharmacology, administration, safety and efficacy data
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Humanos , Criança , Citarabina/uso terapêutico , Aracnoide-Máter/patologia , Neoplasias Meníngeas/tratamento farmacológico , Metástase Neoplásica/patologia , Injeções Espinhais , Neoplasias do Sistema Nervoso Central/patologia , Ependimoma/tratamento farmacológico , Meduloblastoma/tratamento farmacológicoRESUMO
Leptomeningeal dissemination in paediatric central nervous system (CNS) tumours is associated with a poor outcome, and new therapeutic strategies are desperately needed. One of the main difficulties in the treatment of CNS tumours is blood brain barrier penetration. Intrathecal therapy has shown to be effective in several paediatric tumours. The aim of this article is to review the data available on the use of liposomal cytarabine for paediatric patients with leptomeningeal dissemination of CNS tumours, including the pharmacology, administration route, safety and efficacy data.
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Antimetabólitos Antineoplásicos/administração & dosagem , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/patologia , Citarabina/administração & dosagem , Neoplasias Meníngeas/tratamento farmacológico , Adolescente , Criança , Humanos , Lipossomos , Invasividade NeoplásicaRESUMO
We investigated the pathogenicity, invasiveness, and genetic relatedness of 17 clinical Listeria monocytogenes stains isolated over a period of nine years (2006-2014). All isolates were phenotypically characterised and growth patterns were determined. The antimicrobial susceptibility of L. monocytogenes isolates was determined in E-tests. Invasion assays were performed with epithelial HeLa cells. Finally, L. monocytogenes isolates were subtyped by PFGE and MLST. All isolates had similar phenotypic characteristics (ß-haemolysis and lecithinase activity), and three types of growth curve were observed. Bacterial recovery rates after invasion assays ranged from 0.09% to 7.26% (1.62 ± 0.46). MLST identified 11 sequence types (STs), and 14 PFGE profiles were obtained, indicating a high degree of genetic diversity. Genetic studies unequivocally revealed the occurrence of one outbreak of listeriosis in humans that had not previously been reported. This outbreak occurred in October 2009 and affected three patients from neighbouring towns. In conclusion, the molecular epidemiological analysis clearly revealed a cluster (three human cases, all ST1) of not previously reported listeriosis cases in northwestern Spain. Our findings indicate that molecular subtyping, in combination with epidemiological case analysis, is essential and should be implemented in routine diagnosis, to improve the tracing of the sources of outbreaks.
Assuntos
Variação Genética , Listeria monocytogenes/patogenicidade , Listeriose/epidemiologia , Epidemiologia Molecular , Técnicas de Tipagem Bacteriana , Microbiologia de Alimentos , Genótipo , Células HeLa , Humanos , Listeria monocytogenes/isolamento & purificação , Listeriose/genética , Listeriose/microbiologia , EspanhaRESUMO
We compared the diagnostic performance of two chromogenic media, Brilliance MRSA 2 agar (Thermo Fisher Scientific) and ChromID MRSA agar (bioMérieux), for MRSA confirmation of 239 Staphylococcus aureus isolates from clinical, animal and food samples. Statistically significant differences were not observed between MRSA confirmation by mecA/mecC PCR, and by culture in both chromogenic media. However, a statistically significant difference was observed between the results obtained by both chromogenic media (p = 0.003). Segregated analysis of the results depending on the origin of the isolates (clinical, animal, and food) revealed a significant lower performance in the MRSA confirmation of food-derived isolates by using Brilliance MRSA 2 agar in comparison to PCR confirmation (p = 0.003) or ChromID MRSA agar (p<0.001). Both chromogenic media provided a good diagnostic performance for detection of MRSA isolates of human and animal origin. In conclusion, the use of chromogenic agar plates for MRSA confirmation of S. aureus isolates can provide a good diagnostic performance (sensitivity >92% and specificity >89%) regardless of the type of chromogenic media used or the origin of the S. aureus isolates. However, our results revealed a lower diagnostic performance for MRSA confirmation of S. aureus isolates from food samples by using Brilliance MRSA 2 agar.
Assuntos
Compostos Cromogênicos/química , Meios de Cultura/normas , Microbiologia de Alimentos/métodos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Técnicas Microbiológicas/métodos , Ágar , Animais , Meios de Cultura/química , Microbiologia de Alimentos/normas , Humanos , Técnicas Microbiológicas/normas , Reação em Cadeia da Polimerase , Sensibilidade e Especificidade , Infecções Estafilocócicas/microbiologiaRESUMO
Corynebacterium kroppenstedtii has been associated with infections of the female breast. Genome sequencing of two strains revealed a specific genomic island in the multidrug-resistant isolate CNM633/14 with similarity to the R plasmid pJA144188 of Corynebacterium resistens DSM 45100, being indicative of the horizontal transfer of antibiotic resistance genes to C. kroppenstedtii.