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PURPOSE: Our study aimed to explore real-world treatment scenarios for children and adolescents with neurotrophic tropomyosin receptor kinase (NTRK)-fused tumors, emphasizing access, responses, side effects, and outcomes. PATIENTS AND METHODS: Pooled clinical data from 17 pediatric cases (11 soft-tissue sarcomas, five brain tumors, and one neuroblastoma) treated with larotrectinib and radiologic images for 14 patients were centrally reviewed. Testing for gene fusions was prompted by poor response to treatment, tumor progression, or aggressiveness. RESULTS: Six different NTRK fusion subtypes were detected, and various payment sources for testing and medication were reported. Radiologic review revealed objective tumor responses (OR) in 11 of 14 patients: Complete responses: two; partial responses: nine; and stable disease: three cases. Grades 1 or 2 Common Terminology Criteria for Adverse Events adverse effects were reported in five patients. Regarding the entire cohort's clinical information, 15 of 17 patients remain alive (median observation time: 25 months): four with no evidence of disease and 11 alive with disease (10 without progression). One patient developed resistance to the NTRK inhibitor and died from disease progression while another patient died due to an unrelated cause. CONCLUSION: This real-world study confirms favorable agnostic tumor OR rates to larotrectinib in children with NTRK-fused tumors. Better coordination to facilitate access to medication remains a challenge, particularly in middle-income countries like Brazil.
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Inhibidores de Proteínas Quinasas , Pirazoles , Humanos , Niño , Masculino , Femenino , Adolescente , Pirazoles/uso terapéutico , Preescolar , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Receptor trkA/genética , Receptor trkA/antagonistas & inhibidores , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Sarcoma/tratamiento farmacológico , Sarcoma/genética , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/genética , Lactante , Receptor trkB/genética , Receptor trkC/genética , Ensayos Clínicos como AsuntoRESUMEN
Retinoblastoma, the most common intraocular tumor in childhood, still faces challenges in diagnosis and treatment, particularly in low- and middle-income countries. Identifying strategies to improve the time to diagnosis and access to treatment is crucial to enhance survival rates and preserve ocular health. We conducted a systematic review to identify interventions that have demonstrated potential in addressing these challenges. We performed a comprehensive search across databases until March 2023. Out of the studies reviewed, 21 met the inclusion criteria and were categorized into five main areas: surveillance strategies, genetic counseling, education, public assistance, and international partnership. Despite the obstacles faced, the initiatives identified in this review present acts toward improving the time to diagnosis and access to treatment for retinoblastoma. Based on the extracted data, we propose a comprehensive chain of initiatives. We firmly believe that implementing this chain of initiatives can lead to improved clinical outcomes for retinoblastoma patients.
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Países en Desarrollo , Accesibilidad a los Servicios de Salud , Neoplasias de la Retina , Retinoblastoma , Retinoblastoma/terapia , Retinoblastoma/diagnóstico , Humanos , Neoplasias de la Retina/terapia , Neoplasias de la Retina/diagnósticoRESUMEN
OBJECTIVE: This study investigated the concentrations of neutrophil extracellular traps (NET) and salivary cytokines (IL-1ß, IL-6, IL-8/CXCL8, TNF, and TGF-ß1) in patients undergoing chemotherapy and their associations with oral mucositis (OM) and Candida infection. MATERIALS AND METHODS: This prospective longitudinal study performed at a Brazilian service included 60 adults diagnosed with hematolymphoid diseases. Saliva samples were collected on days D0, D3, D10, and D15. Cytokines were analyzed by ELISA and NET formation by identification of the myeloperoxidase-DNA complex. Oral Candida spp. was cultured. RESULTS: OM occurred in 43.3% of patients and oral candidiasis in 20%. However, 66% of individuals had positive cultures for C. albicans. Higher concentrations of IL-6, IL-8/CXCL8, and TNF and lower concentrations of TGF-ß1 were observed in patients with OM. C. albicans infection contributed to the increase in IL-8/CXCL8, TGF-ß1, and TNF. Individuals with OM or with oral candidiasis had significant reductions in NET formation. In contrast, individuals with C. albicans and with concomitant C. albicans and OM exhibited higher NET formation. CONCLUSION: The kinetics of cytokine levels and NET formation in chemotherapy-induced OM appears to be altered by Candida infection, even in the absence of clinical signs of oral candidiasis.
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Candidiasis Bucal , Citocinas , Trampas Extracelulares , Saliva , Estomatitis , Humanos , Masculino , Femenino , Persona de Mediana Edad , Citocinas/metabolismo , Candidiasis Bucal/microbiología , Estomatitis/microbiología , Estomatitis/metabolismo , Estudios Prospectivos , Adulto , Trampas Extracelulares/metabolismo , Saliva/microbiología , Saliva/metabolismo , Anciano , Estudios Longitudinales , Factor de Crecimiento Transformador beta1/metabolismo , Interleucina-8/metabolismo , Interleucina-8/análisis , Factor de Necrosis Tumoral alfa/metabolismo , Candida albicans , Antineoplásicos , Interleucina-6/análisis , Interleucina-6/metabolismo , Interleucina-1beta/metabolismo , Neoplasias Hematológicas/complicacionesRESUMEN
A insuficiência cardíaca aguda (ICA) é uma das causas mais comuns de internação hospitalar, associada a um alto risco de mortalidade. O tratamento atual é principalmente sintomático, sendo os exames laboratoriais realizados, a fim de complementar a avaliação clínica no diagnóstico e auxiliar no estabelecimento do perfil de risco admissional e prognóstico. Este estudo teve como objetivo caracterizar o perfil clínico, farmacoterapêutico e laboratorial de pacientes internados com insuficiência cardíaca aguda em hospital referência regional. Trata-se de um estudo transversal retrospectivo, descritivo, de abordagem quantitativa. Os participantes do estudo foram aqueles com alta médica por ICA pela classificação Internacional de Doenças (CID-10), admitidos na sala de emergência. Excluindo-se a participação de pacientes com tempo de internação inferior a 24 horas, menores de 18 anos. Para análise estatística foi usado o programa SPSS versão 21.0. Quanto ao perfil farmacoterapêutico, os medicamentos mais frequentes foram os que atuam no aparelho cardiovascular e aparelho digestivo e metabolismo, sendo a furosemida o fármaco mais frequente. A análise entre as alterações laboratoriais e a escala de ADHERE, revelou diferença estatística significativa entre os pacientes com risco baixo e risco intermediário/alto nos valores de hemoglobina (p=0,005), TGO (p=0,001), creatinina (p=0,000), ureia (p=0,000), potássio (p=0,004), TTPA (p=0,004) e RNI (p=0,021). Concluiu-se que os medicamentos frequentemente corresponderam ao tratamento recomendado no manejo inicial de pacientes com ICA. O risco de mortalidade intra-hospitalar intermediário/alto de acordo com a escala de ADHERE estavam associados com alterações laboratoriais dos pacientes com ICA.
Acute heart failure (AHF) is one of the most common causes of hospitalization, associated with a high risk of mortality. The current treatment is mainly symptomatic, and laboratory tests are carried out in order to complement the clinical evaluation in the diagnosis and help in establishing the admission and prognostic risk profile. This study aimed to characterize the clinical, pharmacotherapeutic and laboratory profile of patients hospitalized with acute heart failure in a regional reference hospital. This is a retrospective, descriptive, cross-sectional study with a quantitative approach. Study participants were those discharged due to AHF according to the International Classification of Diseases (ICD-10), admitted to the emergency room. Excluding the participation of patients with hospitalization time of less than 24 hours, under 18 years old. For statistical analysis, SPSS version 21.0 was used. As for the pharmacotherapeutic profile, the most frequent drugs were those that act on the cardiovascular and digestive systems and metabolism, with furosemide being the most frequent drug. The analysis between laboratory changes and the ADHERE scale revealed a statistically significant difference between patients at low risk and intermediate/high risk in hemoglobin (p=0.005), TGO (p=0.001), creatinine (p=0.000) values, urea (p=0.000), potassium (p=0.004), APTT (p=0.004) and INR (p=0.021). It was concluded that the medications often corresponded to the recommended treatment in the initial management of patients with AHF. Intermediate/high risk of in-hospital mortality according to the ADHERE scale were associated with laboratory alterations in patients with AHF.
La insuficiencia cardiaca aguda (ICA) es una de las causas más frecuentes de hospitalización, asociada a un alto riesgo de mortalidad. El tratamiento actual es principalmente sintomático y se realizan pruebas de laboratorio para complementar la evaluación clínica en el diagnóstico y ayudar a establecer el perfil de riesgo de ingreso y pronóstico. Este estudio tuvo como objetivo caracterizar el perfil clínico, farmacoterapéutico y de laboratorio de pacientes hospitalizados con insuficiencia cardíaca aguda en un hospital regional de referencia. Se trata de un estudio retrospectivo, descriptivo, transversal con enfoque cuantitativo. Los participantes del estudio fueron los dados de alta por ICA según la Clasificación Internacional de Enfermedades (CIE-10), ingresados en urgencias. Se excluye la participación de pacientes con tiempo de hospitalización menor a 24 horas, menores de 18 años. Para el análisis estadístico se utilizó SPSS versión 21.0. En cuanto al perfil farmacoterapéutico, los fármacos más frecuentes fueron los que actúan sobre los sistemas cardiovascular, digestivo y el metabolismo, siendo la furosemida el fármaco más frecuente. El análisis entre los cambios de laboratorio y la escala ADHERE reveló una diferencia estadísticamente significativa entre los pacientes de riesgo bajo e intermedio/alto en los valores de hemoglobina (p=0,005), TGO (p=0,001), creatinina (p=0,000), urea (p =0,000), potasio (p=0,004), APTT (p=0,004) e INR (p=0,021). Se concluyó que los medicamentos correspondían muchas veces al tratamiento recomendado en el manejo inicial de pacientes con ICA. El riesgo intermedio/alto de mortalidad hospitalaria según la escala ADHERE se asoció con alteraciones de laboratorio en pacientes con ICA.
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Abstract Objective The aim of this study was to analyze the effects of fluid overload related to mechanical ventilation, renal replacement therapy, and evolution to discharge or death in critically ill children. Methods A retrospective study in a Pediatric Intensive Care Unit for two years. Patients who required invasive ventilatory support and vasopressor and/or inotropic medications were considered critically ill. Results 70 patients were included. The mean age was 6.8 ± 6 years. There was a tolerable increase in fluid overload during hospitalization, with a median of 2.45% on the first day, 5.10% on the third day, and 8.39% on the tenth day. The median fluid overload on the third day among those patients in pressure support ventilation mode was 4.80% while the median of those who remained on controlled ventilation was 8.45% (p = 0.039). Statistical significance was observed in the correlations between fluid overload measurements on the first, third, and tenth days of hospitalization and the beginning of renal replacement therapy (p = 0.049) and between renal replacement therapy and death (p = 0.01). The median fluid overload was 7.50% in patients who died versus 4.90% in those who did not die on the third day of hospitalization (p = 0.064). There was no statistically significant association between death and the variables sex or age. Conclusions The fluid overload on the third day of hospitalization proved to be a determinant for the clinical outcomes of weaning from mechanical ventilation, initiation of renal replacement therapy, discharge from the intensive care unit, or death among these children.
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The demands for dental materials continue to grow, driven by the desire to reach a better performance than currently achieved by the available materials. In the dental restorative ceramic field, the structures evolved from the metal-ceramic systems to highly translucent multilayered zirconia, aiming not only for tailored mechanical properties but also for the aesthetics to mimic natural teeth. Ceramics are widely used in prosthetic dentistry due to their attractive clinical properties, including high strength, biocompatibility, chemical stability, and a good combination of optical properties. Metal-ceramics type has always been the golden standard of dental reconstruction. However, this system lacks aesthetic aspects. For this reason, efforts are made to develop materials that met both the mechanical features necessary for the safe performance of the restoration as well as the aesthetic aspects, aiming for a beautiful smile. In this field, glass and high-strength core ceramics have been highly investigated for applications in dental restoration due to their excellent combination of mechanical properties and translucency. However, since these are recent materials when compared with the metal-ceramic system, many studies are still required to guarantee the quality and longevity of these systems. Therefore, a background on available dental materials properties is a starting point to provoke a discussion on the development of potential alternatives to rehabilitate lost hard and soft tissue structures with ceramic-based tooth and implant-supported reconstructions. This review aims to bring the most recent materials research of the two major categories of ceramic restorations: ceramic-metal system and all-ceramic restorations. The practical aspects are herein presented regarding the evolution and development of materials, technologies applications, strength, color, and aesthetics. A trend was observed to use high-strength core ceramics type due to their ability to be manufactured by CAD/CAM technology. In addition, the impacts of COVID-19 on the market of dental restorative ceramics are presented.
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COVID-19 , Materiales Dentales , Humanos , Materiales Dentales/química , Cerámica/química , Diseño Asistido por Computadora , Porcelana Dental , Circonio/química , Ensayo de Materiales , Propiedades de SuperficieRESUMEN
RATIONALE: To understand the risk factors for catheter-related infection during treatment of pediatric cancer is essential to implement measures to prevent its occurrence. BACKGROUND: We performed a comprehensive systematic review of the literature with meta-analysis to identify and synthesize the main risk factors for catheter-related infection in children undergoing oncological treatment. METHODS: Systematic searches were conducted in Medline, Embase, Lilacs, and BVS (Biblioteca Virtual em Saúde) until January 2022, following PRISMA guidelines. The search was not limited to language or dates. Risk factors were divided into host-related, assistance-related, and catheter types. We also describe the most common pathogens. RESULTS: Thirteen studies were included in the review. Diagnosis of hematological neoplasm, the intensity of treatment, blood transfusion in the 4-7 days before the infection, type of long-term catheters (tunneled externalized catheters, double lumen, greater diameter), inpatient treatment, and a longer period of hospitalization were the most consistent risk factors. Metanalysis showed that neutropenia at the moment of catheter placement is not a risk factor for central-line-associated bloodstream infections, however, there is high heterogeneity between studies. Staphylococcus epidermidis was the most common pathogen reported. CONCLUSIONS: Understanding risk factors is an essential step to reduce morbidity and mortality of catheter-related infection. Education for preventive measures, reduction of hospitalization, wisely choosing the most adequate type of catheter, and the best moment for catheter insertion may reduce the occurrence of catheter-related infection.
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Infecciones Relacionadas con Catéteres , Cateterismo Venoso Central , Catéteres Venosos Centrales , Neoplasias , Niño , Humanos , Infecciones Relacionadas con Catéteres/prevención & control , Cateterismo , Catéteres Venosos Centrales/efectos adversos , Factores de Riesgo , Neoplasias/complicaciones , Cateterismo Venoso Central/efectos adversosRESUMEN
BACKGROUND: Obese individuals have higher rates of cancer incidence and cancer- related mortality. The worse chemotherapy outcomes observed in this subset of patients are multifactorial, including the altered physiology in obesity and its impact on pharmacokinetics, the possible increased risk of underdosing, and treatment-related toxicity. AIMS: The present review aimed to discuss recent data on physiology, providing just an overall perspective and pharmacokinetic alterations in obesity concerning chemotherapy. We also reviewed the controversies of dosing adjustment strategies in adult and pediatric patients, mainly addressing the use of actual total body weight and ideal body weight. METHODS: This narrative review tried to provide the best evidence to support antineoplastic drug dosing strategies in children, adolescents, and adults. RESULTS: Cardiovascular, hepatic, and renal alterations of obesity can affect the distribution, metabolism, and clearance of drugs. Anticancer drugs have a narrow therapeutic range, and variations in dosing may result in either toxicity or underdosing. Obese patients are underrepresented in clinical trials that focus on determining recommendations for chemotherapy dosing and administration in clinical practice. After considering associated comorbidities, the guidelines recommend that chemotherapy should be dosed according to body surface area (BSA) calculated with actual total body weight, not an estimate or ideal weight, especially when the intention of therapy is the cure. CONCLUSION: The actual total body weight dosing appears to be a better approach to dosing anticancer drugs in both adults and children when aiming for curative results, showing no difference in toxicity and no limitation in treatment outcomes compared to adjusted doses.
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Antineoplásicos , Neoplasias , Adulto , Adolescente , Humanos , Niño , Peso Corporal/fisiología , Obesidad/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Preparaciones FarmacéuticasRESUMEN
OBJECTIVE: The aim of this study was to analyze the effects of fluid overload related to mechanical ventilation, renal replacement therapy, and evolution to discharge or death in critically ill children. METHODS: A retrospective study in a Pediatric Intensive Care Unit for two years. Patients who required invasive ventilatory support and vasopressor and/or inotropic medications were considered critically ill. RESULTS: 70 patients were included. The mean age was 6.8 ± 6 years. There was a tolerable increase in fluid overload during hospitalization, with a median of 2.45% on the first day, 5.10% on the third day, and 8.39% on the tenth day. The median fluid overload on the third day among those patients in pressure support ventilation mode was 4.80% while the median of those who remained on controlled ventilation was 8.45% (pâ¯=â¯0.039). Statistical significance was observed in the correlations between fluid overload measurements on the first, third, and tenth days of hospitalization and the beginning of renal replacement therapy (pâ¯=â¯0.049) and between renal replacement therapy and death (pâ¯=â¯0.01). The median fluid overload was 7.50% in patients who died versus 4.90% in those who did not die on the third day of hospitalization (pâ¯=â¯0.064). There was no statistically significant association between death and the variables sex or age. CONCLUSIONS: The fluid overload on the third day of hospitalization proved to be a determinant for the clinical outcomes of weaning from mechanical ventilation, initiation of renal replacement therapy, discharge from the intensive care unit, or death among these children.
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Enfermedad Crítica , Desequilibrio Hidroelectrolítico , Niño , Humanos , Lactante , Preescolar , Estudios Retrospectivos , Enfermedad Crítica/terapia , Desequilibrio Hidroelectrolítico/etiología , Desequilibrio Hidroelectrolítico/terapia , Unidades de Cuidado Intensivo Pediátrico , Terapia de Reemplazo Renal , Unidades de Cuidados IntensivosRESUMEN
INTRODUCTION: Febrile neutropenia (FN) is a serious complication of cancer chemotherapy. The present study aimed to identify risk factors for documented infection in pediatric patients with FN and cancer. METHODS: This prospective cohort study included patients under 18 years from 2016 to 2018. Infection was defined according to the Centers for Disease Control and Prevention criteria. RESULTS: A total of 172 febrile neutropenic episodes were evaluated. From univariate analysis, the risk factors were: female gender; monocyte count < 100 cell/mm³, platelets < 50,000, C-reactive protein (CRP) > 90 mg/dl and hemoglobin < 7mg/dl at the onset of an episode; two or more episodes of FN, and; fever onset; positive blood culture at the fever onset. Independent risk factors according to the multivariate analysis were: CRP at the onset of a febrile episode > 90mg/dl, fever onset and first blood culture with a positive result. The lowest probability of infection was related to first episode and to platelets > 50,000 at the onset of fever. CONCLUSION: A CRP > 90 at the onset of a febrile episode, platelets < 50,000, second episode or more, first fever episode during hospitalization and positive first blood culture were found to be associated with a higher risk of infection and they could be useful for the establishment of risk scores for infection in neutropenic children.
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Abstract The demands for dental materials continue to grow, driven by the desire to reach a better performance than currently achieved by the available materials. In the dental restorative ceramic field, the structures evolved from the metal-ceramic systems to highly translucent multilayered zirconia, aiming not only for tailored mechanical properties but also for the aesthetics to mimic natural teeth. Ceramics are widely used in prosthetic dentistry due to their attractive clinical properties, including high strength, biocompatibility, chemical stability, and a good combination of optical properties. Metal-ceramics type has always been the golden standard of dental reconstruction. However, this system lacks aesthetic aspects. For this reason, efforts are made to develop materials that met both the mechanical features necessary for the safe performance of the restoration as well as the aesthetic aspects, aiming for a beautiful smile. In this field, glass and high-strength core ceramics have been highly investigated for applications in dental restoration due to their excellent combination of mechanical properties and translucency. However, since these are recent materials when compared with the metal-ceramic system, many studies are still required to guarantee the quality and longevity of these systems. Therefore, a background on available dental materials properties is a starting point to provoke a discussion on the development of potential alternatives to rehabilitate lost hard and soft tissue structures with ceramic-based tooth and implant-supported reconstructions. This review aims to bring the most recent materials research of the two major categories of ceramic restorations: ceramic-metal system and all-ceramic restorations. The practical aspects are herein presented regarding the evolution and development of materials, technologies applications, strength, color, and aesthetics. A trend was observed to use high-strength core ceramics type due to their ability to be manufactured by CAD/CAM technology. In addition, the impacts of COVID-19 on the market of dental restorative ceramics are presented.
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Abstract Introduction Febrile neutropenia (FN) is a serious complication of cancer chemotherapy. The present study aimed to identify risk factors for documented infection in pediatric patients with FN and cancer. Methods This prospective cohort study included patients under 18 years from 2016 to 2018. Infection was defined according to the Centers for Disease Control and Prevention criteria. Results A total of 172 febrile neutropenic episodes were evaluated. From univariate analysis, the risk factors were: female gender; monocyte count < 100 cell/mm³, platelets < 50,000, C-reactive protein (CRP) > 90 mg/dl and hemoglobin < 7mg/dl at the onset of an episode; two or more episodes of FN, and; fever onset; positive blood culture at the fever onset. Independent risk factors according to the multivariate analysis were: CRP at the onset of a febrile episode > 90mg/dl, fever onset and first blood culture with a positive result. The lowest probability of infection was related to first episode and to platelets > 50,000 at the onset of fever. Conclusion A CRP > 90 at the onset of a febrile episode, platelets < 50,000, second episode or more, first fever episode during hospitalization and positive first blood culture were found to be associated with a higher risk of infection and they could be useful for the establishment of risk scores for infection in neutropenic children.
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Humanos , Masculino , Femenino , Lactante , Preescolar , Niño , Adolescente , Sepsis , Neutropenia Febril , Factores de Riesgo , Bacteriemia , Quimioterapia , NeoplasiasRESUMEN
Abstract Introduction Invasive fungal diseases represent important causes of morbidity and mortality among pediatric oncohematological patients. Acute invasive fungal rhinosinusitis is a rare and aggressive disease that occurs mainly in immunocompromised patients. The mortality rate is high and therefore, accurate and early diagnosis is essential. Objectives The aim of this study was to describe the frequency of acute invasive fungal rhinosinusitis among pediatric oncohematological patients and characterize them with confirmed diagnoses. Methods This was a retrospective study that analyzed the medical records of pediatric patients diagnosed with oncohematological diseases and suspected fungal infections, who were included after obtaining informed consent, from January to December 2017, in the pediatric unit of a tertiary university hospital. Data collected from medical record analysis included the following: underlying diagnosis, absolute neutrophil count, clinical presentation, culture and biopsy results, surgical procedures performed, survival and mortality. Results A total of 27 patients were evaluated, with three suspected cases of acute invasive fungal rhinosinusitis. Histopathological and microbiological analyses confirmed two cases. In both cases, the pathogen isolated in the culture was Fusarium sp. The two confirmed cases were female, aged 12 and 14 years, both with an absolute neutrophil count of 10 cells/μL. The underlying disease of the first patient was acute myeloid leukemia (subtype M5), whereas the second patient presented idiopathic bone marrow aplasia. Conclusion Both confirmed cases of acute invasive fungal rhinosinusitis presented with constitutional symptoms and signs of nasal and sinusital inflammation. This demonstrates the importance of fever as a symptom in immunocompromised patients and it should prompt otorhinolaryngological investigation.
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Humanos , Masculino , Femenino , Lactante , Preescolar , Niño , Adolescente , Fusariosis , Infecciones Fúngicas Invasoras , Enfermedades Hematológicas , Sinusitis , Neutropenia Febril , FusariumRESUMEN
INTRODUCTION: Invasive fungal diseases represent important causes of morbidity and mortality among pediatric oncohematological patients. Acute invasive fungal rhinosinusitis is a rare and aggressive disease that occurs mainly in immunocompromised patients. The mortality rate is high and therefore, accurate and early diagnosis is essential. OBJECTIVES: The aim of this study was to describe the frequency of acute invasive fungal rhinosinusitis among pediatric oncohematological patients and characterize them with confirmed diagnoses. METHODS: This was a retrospective study that analyzed the medical records of pediatric patients diagnosed with oncohematological diseases and suspected fungal infections, who were included after obtaining informed consent, from January to December 2017, in the pediatric unit of a tertiary university hospital. Data collected from medical record analysis included the following: underlying diagnosis, absolute neutrophil count, clinical presentation, culture and biopsy results, surgical procedures performed, survival and mortality. RESULTS: A total of 27 patients were evaluated, with three suspected cases of acute invasive fungal rhinosinusitis. Histopathological and microbiological analyses confirmed two cases. In both cases, the pathogen isolated in the culture was Fusarium sp. The two confirmed cases were female, aged 12 and 14 years, both with an absolute neutrophil count of 10cells/µL. The underlying disease of the first patient was acute myeloid leukemia (subtype M5), whereas the second patient presented idiopathic bone marrow aplasia. CONCLUSION: Both confirmed cases of acute invasive fungal rhinosinusitis presented with constitutional symptoms and signs of nasal and sinusital inflammation. This demonstrates the importance of fever as a symptom in immunocompromised patients and it should prompt otorhinolaryngological investigation.
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Escorbuto , Ácido Ascórbico/uso terapéutico , Niño , Dieta , Humanos , Escorbuto/diagnóstico , Escorbuto/etiologíaRESUMEN
Fish are often used as bioindicators of the presence of potentially toxic metals in aquatic ecosystems. The objective of these study was to quantify the levels of Cd, Cr, Cu, Hg, Pb and Zn in water and sediment samples from the Sorocaba River and musculature and gill samples of seven species of fish (Hoplosternum littorale, Pterygoplichthys ambrosettii, Hypostomus ancistroides, Geophagus iporangensis, Prochilodus lineatus, Psalidodon cf. fasciatus, and Rhamdia quelen. In addition, the Bioaccumulation factor and Bioconcentration factor were obtained. The water and sediment analysis indicates average concentrations of metals below the maximum limit allowed by Brazilian legislation. Results above the legislation were found for chromium, in 18 samples: eight gills and 10 muscles. The trophic group that presented the highest contamination was the iliophages, followed by insectivores. There were no significant differences between the trophic groups in the absorption of the analyzed metals except for Zn and Hg in fish gills. The bioaccumulation factor in the gills and muscles showed that Hg and Zn had the highest values for the sediment in most species studied. Future research is needed to broaden the assessment as fish are consumed and water collection for supply has recently started downstream of the studied area.(AU)
Peixes são frequentemente usados como bioindicadores da presença de metais potencialmente tóxicos em ecossistemas aquáticos. O objetivo deste estudo foi quantificar as concentrações de Cd, Cr, Cu, Hg, Pb e Zn em amostras de água e sedimento do rio Sorocaba e em amostras de musculatura e brânquias de sete espécies de peixes (Hoplosternum littorale, Pterygoplichthys ambrosettii, Hypostomus ancistroides, Geophagus iporangensis, Prochilodus lineatus, Psalidodon cf. fasciatus e Rhamdia quelen), pertencentes a diferentes níveis tróficos. Além disso, foi obtido o fator de bioacumulação e o fator de bioconcentração. A análise de água e sedimento indicaram concentrações médias de metais abaixo do limite máximo permitido pela legislação brasileira. Foram encontrados valores acima da legislação principalmente para o cromo: oito brânquias e 10 músculos. O grupo trófico que apresentou maior contaminação foi o iliófago, seguido pelos insetívoros. Não foi verificado diferenças significativas entre os grupos tróficos na absorção dos metais analisados, exceto para zinco e mercúrio em brânquias de peixes. O fator de bioacumulação nas brânquias e músculos mostrou que Hg e Zn apresentaram os maiores valores para o sedimento na maioria das espécies estudadas. Pesquisas futuras são necessárias para ampliar a avaliação à medida que os peixes são consumidos e a coleta de água para abastecimento começou recentemente a jusante da área de estudo.(AU)
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Animales , Peces , Intoxicación por Metales Pesados , Química del Agua , BioacumulaciónRESUMEN
Our group recently showed that the (ASNase) formulation available in Brazil from 2017 to 2018 when used at the same dose and frequency as the formulation provided previously did not reach the activity considered therapeutic. Based on these, our goal was to assess the impact of these facts on the prognosis of children with ALL at different oncology centers. A multicentre retrospective observational study followed by a prospective follow-up. Patients aged >1 and <18 years in first-line treatment followed up at 10 referral centres, between 2014 and 2018 who received the formulation Leuginase® were identified (Group B). For each patient, the centre registered 2 patients who received ASNase in the presentation of Aginasa® exclusively (Group A). Data collection was registered using (Redcap® ). A total of 419 patients were included; 282 in Group A and 137 in B. Group A had a 3-year OS and EFS of 91·8% and 84·8% respectively, while Group B had a 3-year OS of 83·8% (P = 0·003) and EFS of 76·1% (P = 0·008). There was an impact on 3-year OS and EFS of children who received a formulation. This result highlights the importance of evaluating ASNase and monitoring its activity.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Asparaginasa/farmacología , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Asparaginasa/administración & dosificación , Brasil/epidemiología , Niño , Preescolar , Composición de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Lactante , Estimación de Kaplan-Meier , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Supervivencia sin Progresión , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
Cases of respiratory diseases have been increasing around the world, affecting the health and quality of life of millions of people every year. Chronic respiratory diseases (CRDs) and acute respiratory infections (ARIs) are responsible for many hospital admissions and deaths, requiring sophisticated treatments that facilitate the delivery of therapeutics to specific target sites with controlled release. In this context, different nanoparticles (NPs) have been explored to match this demand, such as lipid, liposome, protein, carbon-based, polymeric, metallic, oxide, and magnetic NPs. The use of NPs as drug delivery systems can improve the efficacy of commercial drugs due to their advantages related to sustained drug release, targeting effects, and patient compliance. The current review presents an updated summary of recent advances regarding the use of NPs as drug delivery systems to treat diseases related to the respiratory tract, such as CRDs and ARIs. The latest applications presented in the literature were considered, and the opportunities and challenges of NPs in the drug delivery field are discussed.
Asunto(s)
Antiinfecciosos/uso terapéutico , Sistemas de Liberación de Medicamentos , Nanopartículas/química , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Animales , Antiinfecciosos/química , HumanosRESUMEN
NEW FINDINGS: What is the central question of this study? Do mice submitted to sustained hypoxia present autonomic and respiratory changes similarly to rats? What is the main finding and its importance? Arterial pressure in the normal range, reduced baseline heart rate and tachypnoea were observed in behaving sustained hypoxia mice. Recordings in the in situ preparation of mice submitted to sustained hypoxia show an increase in cervical vagus nerve activity and a simultaneous reduction in thoracic sympathetic nerve activity correlated with changes in the respiratory cycle. Therefore, mice are an important model for studies on the modulation of sympathetic activity to the cardiovascular system and the vagus innervation of the upper airways due to changes in the respiratory network induced by sustained hypoxia. ABSTRACT: Short-term sustained hypoxia (SH) in rats induces sympathetic overactivity and hypertension due to changes in sympathetic-respiratory coupling. However, there are no consistent data about the effect of SH on mice due to the different protocols of hypoxia and difficulties associated with the handling of these rodents under different experimental conditions. In situ recordings of autonomic and respiratory nerves in SH mice have not been performed yet. Herein, we evaluated the effects of SH ( FiO2 = 0.1 for 24 h) on baseline mean arterial pressure (MAP), heart rate (HR), respiratory frequency (fR ) and responses to chemoreflex activation in behaving SH mice. A characterization of changes in cervical vagus (cVN), thoracic sympathetic (tSN), phrenic (PN) and abdominal (AbN) nerves in SH mice using the in situ working heart-brainstem preparation was also performed. SH mice presented normal MAP, significant reduction in baseline HR, increase in baseline fR , as well as increase in the magnitude of bradycardic response to chemoreflex activation. In in situ preparations, SH mice presented a reduction in PN discharge frequency, and increases in the time of expiration and incidence of late-expiratory bursts in AbN activity. Nerve recordings also indicated a significant increase in cVN activity and a significant reduction in tSN activity during expiration in SH mice. These findings make SH mice an important experimental model for better understanding how changes in the respiratory network may impact on the modulation of vagal control to the upper airways, as well as in the sympathetic activity to the cardiovascular system.