Impact of Time-to-Antibiotic Delivery in Pediatric Patients With Cancer Presenting With Febrile Neutropenia.

PURPOSE: Febrile neutropenia (FN) in pediatric patients with cancer can cause severe infections, and prompt antibiotics are warranted. Extrapolated from other populations, a time-to-antibiotic (TTA) metric of <60 minutes after medical center presentation was established, with compliance data factoring into pediatric oncology program national rankings. METHODS: All FN episodes occurring at Vanderbilt Children's Hospital (2007-February 2022) and a sample of episodes from Colorado Children's Hospital (2012-2019) were abstracted, capturing TTA and clinical outcomes including major complications (intensive care unit [ICU] admission, vasopressors, intubation, or infection-related mortality). Odds ratios (ORs) were adjusted for age, treatment center, absolute neutrophil count, hypotension presence, stem-cell transplant status, and central line type. RESULTS: A total of 2,349 episodes were identified from Vanderbilt (1,920) and Colorado (429). Only 0.6% (n = 14) episodes required immediate ICU management, with a median TTA of 28 minutes (IQR, 20-37). For the remaining patients, the median TTA was 56 minutes (IQR, 37-90), and 54.3% received antibiotics in <60 minutes. There were no significant associations between TTA (<60 or ≥60 minutes) and major complications (adjusted OR, 0.99 [95% CI, 0.62 to 1.59]; P = .98), and a TTA ≥60 minutes was not associated with any type of complication. Similarly, TTA, when evaluated as a continuous variable, was not associated with a major (OR, 0.99 [95% CI, 0.94 to 1.04]; P = .69) nor any other complication in adjusted analysis. CONCLUSION: There is no clear evidence that a reduced TTA improves clinical outcomes in pediatric oncology FN and thus it should not be used as a primary quality measure.

Generation of innocents become enduring victims of a terrible war: Vulnerabilities of children and adolescents in Syria.

Estimates suggest that so far in 2021, about two children have died each week at Al Hol camp in northeast Syria. Current evidence states that more than 90% of children are under the age of 12, and that they face circumstances contrasting with severely restricted freedoms and human rights violations. They do not have access to clean water or adequate food. Recent examples of violence and fears of a massive outbreak of COVID-19 only increase the suffering. In this context, the global debate discusses exposure to these conditions and their psychological and physical effects on children's well-being, mainly due to reports of sexual violence, exploitation, harassment, trafficking, and indoctrination. It is important to emphasize that girls are particularly vulnerable to sexual abuse, needing gender-specific support through their physical and psychological pain.

Echoes of Global Silence: Is there protection and safety for Venezuelan children and adolescents?

As the crisis in Venezuela deepens, an increasing number of children urgently needs shelter, protection, and access to basic services, including food, medicine, clean water, and sanitation. Children and young people in transit are particularly at risk of criminal activity or being separated from their families. The consequences of the humanitarian crisis for children could be devastating for the country's future. The child labor problem was fueled by a mass migration of more than five million Venezuelans that turned many children into livelihoods for their families. The pandemic has aggravated risk factors for child labor. The work ranges from working in dumps to agricultural fields, adding that children in rural areas are more likely to depend on public assistance and are at greater risk of being recruited by gangs. Some Venezuelan women and girls are traveling for hours or days to cross the Colombian border and earn money as sex workers. The complex and multifaceted reality of international migration reveals enormous challenges that directly affect the lives of children and adolescents, especially the most vulnerable, and demand urgent responses from the constituted powers and civil society in the face of countless human rights violations those people experience.

Filtered Cerebrospinal Fluid From Patients With Amyotrophic Lateral Sclerosis Displays an Altered Proteome and Affects Motor Phenotype in a Mouse Model.

INTRODUCTION: Cerebrospinal fluid (CSF) has been implicated in amyotrophic lateral sclerosis (ALS) due to its ability to spread inflammatory proteins throughout the nervous system. We hypothesized that filtration of the CSF could remove pathogenic proteins and prevent them from altering motor phenotypes in a mouse model. METHODS: We filtered the CSF from 11 ALS patients via 100 kilodaltons (kD) molecular weight cut-off filters. We used mass spectrometry-based discovery proteomics workflows to compare protein abundances before and after filtration. To test the effects of CSF filtration on motor function, we injected groups of mice with saline, filtered ALS-CSF, or unfiltered ALS-CSF (n=12 per group) and assessed motor function via pole descent and open field tests. RESULTS: We identified proteins implicated in ALS pathogenesis and showed that these were removed in significant amounts in our workflow. Key filtered proteins included complement proteins, chitinases, serine protease inhibitors, and neuro-inflammatory proteins such as amyloid precursor protein, chromogranin A, and glial fibrillary acidic protein. Compared to the filtered ALS-CSF mice, unfiltered ALS-CSF mice took longer to descend a pole (10 days post-injection, 11.14 seconds vs 14.25 seconds, p = 0.02) and explored less on an open field (one day post-injection, 21.81 m vs 16.83 m, p = 0.0004). CONCLUSIONS: We demonstrated the ability to filter proteins from the CSF of ALS patients and identified potentially pathologic proteins that were reduced in quantity. Additionally, we demonstrated the ability of unfiltered ALS-CSF to induce motor deficits in mice on the pole descent and open field tests and showed that filtration could prevent this deficit. Given the lack of effective treatments for ALS, this could be a novel solution for patients suffering from this deadly and irreversible condition.

Evaluation of neurapheresis therapy in vitro: a novel approach for the treatment of leptomeningeal metastases.

BACKGROUND: Leptomeningeal metastases (LM), late-stage cancer when malignant cells migrate to the subarachnoid space (SAS), have an extremely poor prognosis. Current treatment regimens fall short in effectively reducing SAS tumor burden. Neurapheresis therapy is a novel approach employing filtration and enhanced circulation of the cerebrospinal fluid (CSF). Here, we examine the in vitro use of neurapheresis therapy as a novel, adjunctive treatment option for LM by filtering cells and augmenting the distribution of drugs that may have the potential to enhance the current clinical approach. METHODS: Clinically relevant concentrations of VX2 carcinoma cells were suspended in artificial CSF. The neurapheresis system's ability to clear VX2 carcinoma cells was tested with and without the chemotherapeutic presence (methotrexate [MTX]). The VX2 cell concentration following each filtration cycle and the number of cycles required to reach the limit of detection were calculated. The ability of neurapheresis therapy to circulate, distribute, and maintain therapeutic levels of MTX was assessed using a cranial-spinal model of the SAS. The distribution of a 6 mg dose was monitored for 48 h. An MTX-specific ELISA measured drug concentration at ventricular, cervical, and lumbar sites in the model over time. RESULTS: In vitro filtration of VX2 cancer cells with neurapheresis therapy alone resulted in a 2.3-log reduction in cancer cell concentration in 7.5 h and a 2.4-log reduction in live-cancer cell concentration in 7.5 h when used with MTX. Cranial-spinal model experiments demonstrated the ability of neurapheresis therapy to enhance the circulation of MTX in CSF along the neuraxis. CONCLUSION: Neurapheresis has the potential to act as an adjunct therapy for LM patients and significantly improve the standard of care.

Pyrodextrinization of yam (Dioscorea sp.) starch isolated from tubers grown in Brazil and physicochemical characterization of yellow pyrodextrins.

This study optimizes the pyrodextrinization of yam (Dioscorea sp.) starch isolated from tubers grown in Brazil to produce a yellow pyrodextrin with the lowest enzymatically available starch (AS) content and color difference (ΔE) index. At 140 °C (fixed heating temperature), the effects of acid concentration (0.65 - 2.99 g of HCl/kg of starch) and incubation time (53 - 307 min) on the response variables were evaluated using a response surface methodology. Some physicochemical characteristics were also determined on pyrodextrins. Both factors negatively affected the AS content, although positively influenced the ΔE (P < 0.05). The yellow pyrodextrin produced with 1.82 g/kg and heating for 307 min, presented physicochemical properties similar to the commercial pyrodextrins from potato starch, with 46.6 % of AS, 24.5 of ΔE, high solubility and very low viscosity. The pyrodextrinization caused a decrease of 30 - 54 % in AS content (P < 0.05), making these yam pyrodextrins a promising material for water-soluble and very low viscous dietary fiber.

Pharmacodynamics of Isavuconazole in a Rabbit Model of Cryptococcal Meningoencephalitis.

Cryptococcus spp., important fungal pathogens, are the leading cause of fungus-related mortality in human immunodeficiency virus-infected patients, and new therapeutic options are desperately needed. Isavuconazonium sulfate, a newer triazole antifungal agent, was studied to characterize the exposure-response relationship in a rabbit model of cryptococcal meningoencephalitis. Rabbits treated with isavuconazonium sulfate were compared with those treated with fluconazole and untreated controls. The fungal burden in the cerebrospinal fluid was measured serially over time, while the yeast concentrations in the brain and the eye (aqueous humor) were determined at the end of therapy. The exposure impact of isavuconazonium sulfate dosing in the rabbit was linked using mathematical modeling. Similar significant reductions in the fungal burden in the brain and cerebrospinal fluid in rabbits treated with isavuconazonium sulfate and fluconazole compared with that in the untreated controls were observed. No dose-dependent response was demonstrated with isavuconazonium sulfate treatment in this study. The treatment of cryptococcal meningoencephalitis with isavuconazonium sulfate was similar to that with fluconazole. Dose-dependent reductions in yeast over time were not demonstrated, which limited our ability to estimate the pharmacodynamic target. Further nonclinical and clinical studies are needed in order to characterize the extent of the exposure-response relationship in cryptococcal meningoencephalitis. However, this study suggests that isavuconazonium sulfate, like fluconazole, could be beneficial in the setting of consolidation and maintenance therapy, rather than induction monotherapy, in high-burden cryptococcal meningoencephalitis.

Optimized acid hydrolysis of the polysaccharides from the seaweed Solieria filiformis (Kützing) P.W. Gabrielson for bioethanol production / Hidrólise ácida otimizada dos polissacarídeos da macroalga Solieria filiformis (Kützing) P.W. Gabrielson para produção de bioetanol

The seaweeds are bio-resource rich in sulfated and neutral polysaccharides. The tropical seaweed species used in this study (Solieria filiformis), after dried, shows 65.8% (w/w) carbohydrate, 9.6% (w/w) protein, 1.7% (w/w) lipid, 7.0% (w/w) moisture and 15.9% (w/w) ash. The dried seaweed was easily hydrolyzed under mild conditions (0.5 M sulfuric acid, 20 min.), generating fermentable monosaccharides with a maximum hydrolysis efficiency of 63.21%. Galactose and glucose present in the hydrolyzed were simultaneously fermented by Saccharomyces cerevisiae when the yeast was acclimated to galactose and cultivated in broth containing only galactose. The kinetic parameters of the fermentation of the seaweed hydrolyzed were Y(P/S) = 0.48 ± 0.02 g.g−1, PP = 0.27 ± 0.04 g.L−1.h−1, η = 94.1%, representing a 41% increase in bioethanol productivity. Therefore, S. filiformis was a promising renewable resource of polysaccharides easily hydrolyzed, generating a broth rich in fermentable monosaccharides for ethanol production.

As algas marinhas são recursos naturais ricos em polissacarídeos sulfatados e neutros. A espécie de macroalga tropical utilizada neste estudo (Solieria filiformis) apresentou teores de carboidratos de 65,8% (m/m), proteínas de 9,6% (m/m), lipídios de 1,7% (m/m), umidade de 7,0% (m/m) e 15,9 % (m/m) de cinzas. A macroalga seca foi facilmente hidrolisada em condições brandas, na presença de ácido sulfúrico 0,5 M, por 20 min, produzindo monossacarídeos fermentáveis com uma eficiência de hidrólise máxima de 63,21%. A galactose e a glicose presentes no hidrolisado foram fermentadas simultaneamente por Saccharomyces cerevisiae, após aclimatação da levedura cultivada em meio contendo apenas galactose como fonte de carbono. Os parâmetros cinéticos da fermentação do hidrolisado algáceo pela levedura aclimatada a galactose foram Y(P/S) = 0,48 ± 0,02 g.g-1, PP = 0,27 ± 0,04 g.L- 1.h-1, η = 94,1%. Portanto, a macroalga S. filiformis se mostrou um recurso renovável promissor como fonte de polissacarídeos facilmente hidrolisados, gerando um meio nutritivo rico em glucose e galactose para a produção de etanol.

Incidência de disfagia em Unidade de Terapia Intensiva de adultos / Incidence of disphagia in Intensive Terapy Service of adults

Objetivo: verificar a incidência e o grau de disfagia orofaríngea em indivíduos internados em Unidade de Terapia Intensiva (UTI) e Semi-Intensiva, correlacionando os achados com a doença de base. Métodos: nesse estudo foram avaliados 25 pacientes da UTI e Semi-UTI do Hospital Centro MédicoMaranhense. Os dados foram colhidos por meio de um protocolo de avaliação fonoaudiológica. Resultados: dos 25 pacientes avaliados 18 (74%) apresentaram disfagia orofaríngea, sendo que 11 (61%) tiveram como doença de base lesão neurológica, e 7 (39%) tiveram como doença de base acometimentos não neurológicos. Houve associação significante entre a presença de disfagia e doença de base neurológica. Dos 18 pacientes disfágicos, 8 (45%) apresentaram disfagia de grau leve, 4 (22%)disfagia de grau moderado e 6 (33%) disfagia de grau grave. Deste total, dos pacientes com doença de base neurológica: 03 (27%) apresentaram grau leve, 03 (27%) apresentaram grau moderado e 05 (46%) pacientes apresentaram grau grave. Já os pacientes acometidos por doença de base não neurológica apresentaram: grau leve 05 pacientes (72%), grau moderado 01 paciente (14%) e graugrave 01 paciente (14%). Conclusão: os dados apontam alta incidência de quadros de disfagia orofaríngea em pacientes internados na Unidade de Terapia Intensiva e Semi-intensiva, com associação significante entre a presença de disfagia e doença de base neurológica; o grau grave de disfagiaorofaríngea foi predominante nas doenças de base neurológica, e o grau leve de disfagia orofaríngea foi predominante nas doenças de base não neurológica.

Purpose: to check the incidence and the grade of oropharyngeal dysphagia in individuals under intensive and almost intensive therapy, correlating the data with what was found about the base ill. Methods: in this project, 25 patients from intensive therapy and almost intensive therapy were available from Centro Médico Maranhense Hospital. The information was collected with a speech therapy evaluation. Results: from 25 patients evaluated, 18 (74%) showed oropharyngeal dysphagia, 11 (61%) had as base a neurological ill, and 7 (39%) had as base a non-neurological ill. From 18 patients that had dysphagia,8 (45%) showed a little grade of dysphagia, 4(22%) moderate grade of dysphagia and 6 (33%) a serious grade of dysphagia. About the patients without a neurological base ill problem: light grade 5 patients (72%), moderate grade 01 patient (14%) and had acute grade 01 patient (14%). Conclusion:with the analysis and conclusions obtained, this project show high incidence of oropharyngeal dysphagiain patients at the hospital. In the association and relation between a neurological ill and grade of oropharyngeal dysphagia, the acute grade was predominant, as for the association of patients withouta neurological ill and the grade of oropharingeal dysphagia, the minor showen grade was predominant.