Safety of levofloxacin as an antibiotic prophylaxis in the induction phase of children newly diagnosed with acute lymphoblastic leukemia: an interim analysis of a randomized, open-label trial in Brazil

ABSTRACT Background: Despite high cure rates, treatment-related mortality in children with acute lymphoblastic leukemia (ALL) remains significant. About 4% of patients die during remission induction therapy and approximately two-thirds of treatment-related deaths are due to infectious complications. Methods: From May 2021 to June 2022, children aged one through 18 years, with a recent diagnosis of ALL, admitted to three pediatric oncology centers in Brazil, were enrolled in this multicenter, open-label, randomized, phase 3 clinical trial. Eligible patients were randomly divided into two groups, based on a 1:1 allocation ratio, to receive, or not, levofloxacin as a prophylactic agent during the induction phase. All patients were treated according to the IC-BFM 2009 chemotherapy protocol. Primary endpoints were carbapenemase-producing Enterobacteriaceae (CPE) colonization, Clostridioides difficile diarrhea, and other adverse events related to the use of levofloxacin. The secondary endpoint was febrile neutropenia during induction. The median follow-up was 289 days. Results: Twenty patients were included in this trial, 10 in each group (control and levofloxacin). Mild adverse reactions related to levofloxacin were observed in three patients (30%). Three patients had Clostridioides difficile diarrhea, two in the levofloxacin group and one in the control group (p > 0.99). Only one patient presented colonization by CPE. This patient belonged to the levofloxacin group (p > 0.99). Nine patients presented febrile neutropenia, five in the control group and four in the levofloxacin intervention group (p > 0.99), one patient died due to febrile neutropenia. Conclusion: The use of levofloxacin was shown to be safe in the induction phase in children with de novo ALL. The use of this medication did not increase the rate of colonization by CPE nor the rate of diarrhea by C. difficile. All adverse reactions were mild and remitted either spontaneously or after switching medicine administration from oral to intravenous route.

Epigenetics, hypersensibility and asthma: what do we know so far?

Abstract In this review, we describe recent advances in understanding the relationship between epigenetic changes, especially DNA methylation (DNAm), with hypersensitivity and respiratory disorders such as asthma in childhood. It is clearly described that epigenetic mechanisms can induce short to long-term changes in cells, tissues, and organs. Through the growing number of studies on the Origins of Health Development and Diseases, more and more data exist on how environmental and genomic aspects in early life can induce allergies and asthma. The lack of biomarkers, standardized assays, and access to more accessible tools for data collection and analysis are still a challenge for future studies. Through this review, the authors draw a panorama with the available information that can assist in the establishment of an epigenetic approach for the risk analysis of these pathologies.

From H1N1 to COVID-19: What we have seen in children with hemoglobinopathies

Abstract This work aimed to better understand the impact of pandemics of respiratory viruses on children with hemoglobinopathies through a comprehensive review of the literature. MEDLINE, SCIELO, LILACS, and PUBMED were used as data sources to find articles without time period restrictions. Previous observations suggest that patients with hemoglobinopathies are a group especially susceptible to the complications of viral respiratory infections, with greater morbidity and mortality related to them. Within this context, this review found that, during the 2009 H1N1 pandemic, the risk of hospitalization in children and adults increased, especially in patients with a history of complications such as acute chest syndrome. In addition, the Coronavirus Disease 2019 (COVID-19) pandemic appears to have less repercussion among children with hemoglobinopathies compared to adults, similar to what is seen in the general population. In the H1N1 pandemic, patients with hemoglobinopathies behaved as a group more susceptible to complications, with increased morbidity and mortality. However, for COVID-19, the existing data to date on these patients do not show the same clinical impact. Thus, although these children deserve attention in case of infection due to their potential risks, they seem to have a favorable evolution. Highlights Children with hemoglobinopathies have less severe conditions with Coronavirus 2019 Disease (COVID-19) compared to adults, which is similar to that observed in the general population In the H1N1 pandemic, patients with hemoglobinopathies behaved as the group most susceptible to complications, with increased morbidity and mortality

Are there regional variations in the presentation of childhood leukemia

Introduction: Treatment of childhood acute lymphoblastic leukemia (ALL) is based on risk stratification. This study aimed to assess the agreement between risk group classifications in the different childhood ALL treatment protocols used in a referral hospital in southern Brazil. Methods: We retrospectively reviewed the medical records of patients aged 1 to 18 years with B-cell ALL treated at a hospital from January 2013 to April 2017. Agreement between risk classifications was assessed by the kappa coefficient. Results: Seventy-five patients were analyzed. There was poor agreement between risk stratification by GBTLI 2009 and BFM 95 protocols (kappa = 0.22; p = 0.003) and by GBTLI 2009 and IC-BFM 2002 protocols (kappa = 0.24; p = 0.002). Risk group distribution was 13.3% for low risk, 32.0% for intermediate risk, and 54.7% for high risk based on stratification by the GBTLI 2009 protocol, and 28.0% for low risk, 42.7% for intermediate risk, and 29.3% for high risk based on stratification by the IC-BFM 2002 protocol. Overall survival was 68.6%. Conclusion: This study provides numerous points to ponder about the treatment of leukemia in Brazil. The percentage of patients classified as high risk in our sample was higher than that reported in the international literature. This difference, however, had no impact on overall survival, which was shorter than that reported in the international literature. (AU)

Effect of soybean ureases on seed germination and plant development

Abstract Urease catalyzes the hydrolysis of urea to ammonia and carbon dioxide. The ammonia (nitrogen (N) product of urease activity) is incorporated into organic compounds. Thus, urease is involved in N remobilization, as well as in primary N assimilation. Two urease isoforms have been described for soybean: the embryo-specific, encoded by the Eu1 gene, and the ubiquitous urease, encoded by Eu4. A third urease-encoding gene was recently identified, designated Eu5, which encodes the putative protein product SBU-III. The present study aimed to evaluate the contribution of soybean ureases to seed germination and plant development. Analyses were performed using Eu1/Eu4/Eu5-co-suppressed transgenic plants and mutants of the Eu1 and Eu4 urease structural genes, as well as a urease-null mutant (eu3-a) that activates neither the ubiquitous nor embryo-specific ureases. The co-suppressed plants presented a developmental delay during the first month after germination; shoots and roots were significantly smaller and lighter. Slower development was observed for the double eu1-a/eu4-a mutant and the eu3-a single mutant. The N content in transgenic plants was significantly lower than in non-transgenic plants. Among the mutants, eu3-a presented the lowest and eu1-a the highest N content. Altogether, these results indicate that increased ureolytic activity plays an important role in plant development.