5 research outputs found
Transplante de células-tronco hematopoiéticas no tratamento da leucemia mieloide aguda / Hematopoietic stem cells transplantation in the treatment of acute myeloid leukemia
O presente artigo apresenta uma revisão narrativa de literatura cuja finalidade é analisar os impactos do Transplante de Células-Tronco Hematopoiéticas (TCTH) no tratamento da Leucemia Mieloide Aguda (LMA). O TCTH foi apontado como uma terapia extremamente importante no curso terapêutico da LMA, visando a redução de recidivas e o aumento da sobrevida dos pacientes. Ademais, foram abordadas as duas principais técnicas de TCTH, os transplantes autólogo e alogênico, e os motivos pelos quais ambas técnicas podem ser eleitas como conduta terapêutica. Tal eleição foi correlacionada aos diferentes fatores de risco e de prognóstico, além de fatores citogenéticos e moleculares presentes, de forma individualizada, em cada possível apresentação da LMA. Salientaram-se os impactos positivos do TCTH na vida dos pacientes, bem como exploraram-se as complicações relacionadas a essa terapia, como a Doença do Enxerto Contra o Hospedeiro (DECH), decorrente do TCTH alogênico, e os possíveis quadros infecciosos pós-transplante. Compreende-se que o TCTH é uma abordagem terapêutica bem consolidada e que novos estudos referentes a essa terapia podem ser aplicados para o aumento da expectativa e qualidade de vida dos pacientes
An explainable model of host genetic interactions linked to COVID-19 severity
We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients
Assessment of phenolic herbicide toxicity and mode of action by different assays
A phytotoxicity assay based on seed germination/root elongation has been optimized and used to evaluate the toxic effects of some phenolic herbicides. The method has been improved by investigating the influence of experimental conditions. Lepidium sativum was chosen as the most suitable species, showing high germinability, good repeatability of root length measurements, and low sensitivity to seed pretreatment. DMSO was the most appropriate solvent carrier for less water-soluble compounds. Three dinitrophenols and three hydroxybenzonitriles were tested: dinoterb, DNOC, 2,4-dinitrophenol, chloroxynil, bromoxynil, and ioxynil. Toxicity was also determined using the Vibrio fischeri MicrotoxA (R) test, and a highly significant correlation was found between EC50 values obtained by the two assays. Dinoterb was the most toxic compound. The toxicity of hydroxybenzonitriles followed the order: ioxynil > bromoxynil > chloroxynil; L. sativum exhibited a slightly higher sensitivity than V. fischeri to these compounds. A QSAR analysis highlighted the importance of hydrophobic, electronic, and hydrogen-bonding interactions, in accordance with a mechanism of toxic action based on protonophoric uncoupling of oxidative phosphorylation. The results suggest that the seed germination/root elongation assay with L. sativum is a valid tool for the assessment of xenobiotic toxicity and can be recommended as part of a test battery
VENTILATORY ASSOCIATED BAROTRAUMA IN COVID-19 PATIENTS: A MULTICENTER OBSERVATIONAL CASE CONTROL STUDY (COVI-MIX-STUDY)
Background
The risk of barotrauma associated with different types of ventilatory support is unclear in COVID-
19 patients. The primary aim of this study was to evaluate the effect of the different respiratory
support strategies on barotrauma occurrence; we also sought to determine the frequency of
barotrauma and the clinical characteristics of the patients who experienced this complication.
Methods
This multicentre retrospective case-control study from 1 March 2020 to 28 February 2021 included
COVID-19 patients who experienced barotrauma during hospital stay. They were matched with
controls in a 1:1 ratio for the same admission period in the same ward of treatment. Univariable and
multivariable logistic regression (OR) were performed to explore which factors were associated
with barotrauma and in-hospital death.
Results
We included 200 cases and 200 controls. Invasive mechanical ventilation was used in 39.3% of
patients in the barotrauma group, and in 20.1% of controls (p<0.001). Receiving non-invasive
ventilation (C-PAP/PSV) instead of conventional oxygen therapy (COT) increased the risk of
barotrauma (OR 5.04, 95% CI 2.30 - 11.08, p<0.001), similarly for invasive mechanical ventilation
(OR 6.24, 95% CI 2.86-13.60, p<0.001). High Flow Nasal Oxygen (HFNO), compared with COT,
did not significantly increase the risk of barotrauma. Barotrauma frequency occurred in 1.00%
[95% CI 0.88-1.16] of patients; these were older (p=0.022) and more frequently immunosuppressed
(p=0.013). Barotrauma was shown to be an independent risk for death (OR 5.32, 95% CI 2.82-
10.03, p<0.001).
ConclusionsC-PAP/PSV compared with COT or HFNO increased the risk of barotrauma; otherwise HFNO did
not. Barotrauma was recorded in 1.00% of patients, affecting mainly patients with more severe
COVID-19 disease. Barotrauma was independently associated with mortality.
Trial registration: this case-control study was prospectively registered in clinicaltrial.gov as NCT04897152 (on 21 May 2021).
Keywords: COVID-19, acute respiratory failure, barotrauma, pneumothorax, High Flow Nasal
Cannula, Invasive Mechanical Ventilation