Preoperative and postoperative administration of vitamin C in cardiac surgery patients - settings, dosages, duration, and clinical outcomes: a narrative review.

Vitamin C or ascorbic acid is a water-soluble vitamin capable of directly donating electrons to reactive oxygen species, attenuating electrical remodeling, and cardiac dysfunction in patients undergoing cardiac surgery (CS), considered one of the most effective defenses against free radicals in the blood, thus being one of the first antioxidants consumed during oxidative stress. The aim of this review is to assess the effects of perioperative administration of vitamin C in CS patients. A comprehensive literature search was conducted in order to identify prospective cohort studies and/or randomized controlled trials reporting on the perioperative effects of vitamin C among adult patients undergoing CS. Studies published between January 1980 to December 2022 were included in our search, resulting in a total of 31 articles that met all our inclusion criteria. There seems to be a beneficial effect of vitamin C supplementation in arrhythmias such as in postoperative atrial fibrillation, reduction of ICU length of stay, and hospital length of stay, reduction in postoperative ventilation time, in inotropic demand, and in postoperative fatigue. Vitamin C can act as a scavenger of free radicals to decrease the peroxidation of the lipids present in the cell membrane, and to protect the myocardium postoperatively from ischemia/reperfusion injury, thus attenuating oxidative stress and inflammation. It represents a readily available and cost-effective strategy that could improve the outcome of patients undergoing CS, by reducing the risk of serious cardiovascular adverse events, both perioperatively and postoperatively.

Towards Robustifying Image Classifiers against the Perils of Adversarial Attacks on Artificial Intelligence Systems.

Adversarial machine learning (AML) is a class of data manipulation techniques that cause alterations in the behavior of artificial intelligence (AI) systems while going unnoticed by humans. These alterations can cause serious vulnerabilities to mission-critical AI-enabled applications. This work introduces an AI architecture augmented with adversarial examples and defense algorithms to safeguard, secure, and make more reliable AI systems. This can be conducted by robustifying deep neural network (DNN) classifiers and explicitly focusing on the specific case of convolutional neural networks (CNNs) used in non-trivial manufacturing environments prone to noise, vibrations, and errors when capturing and transferring data. The proposed architecture enables the imitation of the interplay between the attacker and a defender based on the deployment and cross-evaluation of adversarial and defense strategies. The AI architecture enables (i) the creation and usage of adversarial examples in the training process, which robustify the accuracy of CNNs, (ii) the evaluation of defense algorithms to recover the classifiers' accuracy, and (iii) the provision of a multiclass discriminator to distinguish and report on non-attacked and attacked data. The experimental results show promising results in a hybrid solution combining the defense algorithms and the multiclass discriminator in an effort to revitalize the attacked base models and robustify the DNN classifiers. The proposed architecture is ratified in the context of a real manufacturing environment utilizing datasets stemming from the actual production lines.

BCL2L12 improves risk stratification and prediction of BFM-chemotherapy response in childhood acute lymphoblastic leukemia.

Background Risk-adjusted treatment has led to outstanding improvements of the remission and survival rates of childhood acute lymphoblastic leukemia (ALL). Nevertheless, overtreatment-related toxicity and resistance to therapy have not been fully prevented. In the present study, we evaluated for the first time the clinical impact of the apoptosis-related BCL2L12 gene in prognosis and risk stratification of BFM-treated childhood ALL. Methods Bone marrow specimens were obtained from childhood ALL patients upon disease diagnosis and the end-of-induction (EoI; day 33) of the BFM protocol, as well as from control children. Following total RNA extraction and reverse transcription, BCL2L12 expression levels were determined by qPCR. Patients' cytogenetics, immunophenotyping and minimal residual disease (MRD) evaluation were performed according to the international guidelines. Results BCL2L12 expression was significantly increased in childhood ALL and correlated with higher BCL2/BAX expression ratio and favorable disease markers. More importantly, BCL2L12 expression was associated with disease remission, while the reduced BCL2L12 expression was able to predict patients' poor response to BFM therapy, in terms of M2-M3 response and MRD≥0.1% on day 15. The survival analysis confirmed the significantly higher risk of the BFM-treated patients underexpressing BCL2L12 at disease diagnosis for early relapse and worse survival. Lastly, evaluation of BCL2L12 expression clearly strengthened the prognostic value of the established disease prognostic markers, leading to superior prediction of patients' outcome and improved specificity of BFM risk stratification. Conclusions The expression levels of the apoptosis-related BCL2L12 predict response to treatment and survival outcome of childhood ALL patients receiving BFM chemotherapy.

Overexpression of BCL2 and BAX following BFM induction therapy predicts ch-ALL patients' poor response to treatment and short-term relapse.

PURPOSE: The identification of childhood acute lymphoblastic leukemia (ch-ALL) patients who are at a higher risk of chemotherapy resistance and relapse is essential for successful treatment decisions, despite the application of novel therapies. The aim of the study is the evaluation of BCL2 and BAX expression for the prognosis of ch-ALL patients treated with Berlin-Frankfurt-Münster (BFM) backbone protocol. METHODS: Bone marrow specimens were obtained at the time of diagnosis and on day 33 following BFM treatment induction from 82 ch-ALL patients, as well as from 63 healthy children. Following extraction, total RNA was reverse transcribed and BCL2 and BAX expression levels were determined by qPCR. RESULTS: BCL2 expression and BCL2/BAX ratio were strongly upregulated in ch-ALL compared to healthy children and were correlated with favorable prognostic disease features. Increased levels of BCL2 and BAX expression were associated with disease remission, as ch-ALL patients with lower expression ran a significantly higher risk of M2-M3 response, positive MRD and poor survival outcome. Moreover, the upregulation of BCL2 and BAX following BFM treatment induction was shown to represent an independent predictor of patients' short-term relapse, which was further confirmed in ch-ALL patients with favorable prognostic markers. CONCLUSIONS: In conclusion, BCL2 and BAX could be effectively used for an enhanced prediction of BFM-treated patients' outcome.

Immunoassay-based serum hepcidin reference range measurements in healthy children: differences among age groups.

BACKGROUND: Hepcidin is a peptide hormone that plays a key role in regulating iron absorption from the small intestine and body iron distribution. Alterations in hepcidin concentrations have been associated with chronic inflammatory conditions or inherited diseases of iron metabolism. The aim of our study was to evaluate healthy children in order to define normal reference range of serum hepcidin concentrations. The universal use of a reliable commercial ELISA kit gives the ability to compare our results with those from previous studies. METHODS: We evaluated 180 healthy children (88 boys, mean age: 67.55 ± 39.26 months, median: 60, range: 24-156 months) aged 2-12 years, using an immunoassay kit. RESULTS: Hepcidin median values were 46.94 ng/ml for boys and 46.79 ng/ml for girls. No significant differences were observed between boys and girls. There seem to be significantly higher values of hepcidin in older children (10-12 years old). This trend was constant and statistically significant in boys after gender and age group stratification. Although this trend was more prominent in girls, it was not statistically significant. CONCLUSIONS: This study aims at setting up reference values for serum hepcidin concentrations in healthy pediatric population by using a well-established laboratory kit. The difference in hepcidin concentrations in older children could be attributed to different growth rates. Additionally, differences between values in adults and children could reflect alterations in iron metabolism between those two age groups.

Acute megakaryoblastic leukemia with increased hematogones in children.

We describe 2 patients, a 4-month-old male and a 17-month-old female, with de novo acute megakaryoblastic leukemia with increased number of hematogones at diagnosis. Both children were admitted in the hospital with thrombocytopenia. The bone marrow smears in the first child revealed the presence of 60% cells with morphologic features consistent with acute megakaryoblastic leukemia. In the other, the initial bone marrow aspirate was dry tap but on the following aspirate 10% cells with lymphoblastic morphology could be seen. The bone marrow flow cytometry showed the presence of hematogones-38% in the first case and 20% in the second-with absence of blasts. Repeated bone marrow aspirates, trephines, and immunophenotypic as well as molecular studies, confirmed the diagnosis of M7. Both children were treated according to the Berlin-Frankfurt-Munster 2004 protocol.

Serum hepcidin and ferritin to iron ratio in evaluation of bacterial versus viral infections in children: a single-center study.

BACKGROUND: Differential diagnosis of childhood infections is important. Several biochemical indices steer diagnosis toward bacterial agents, although the data are often not definitive. Hepcidin is a central component of blood iron, and ferritin alterations occur during infections. We measured hepcidin changes and evaluated ferritin to iron ratio (FIR) in patients with suspected infections. METHODS: We studied 69 children with infection and an equal number of matched controls during a 3-year period. A bacterial agent was demonstrated in 17 and a viral pathogen in 52 of the patients. Hematologic and biochemical tests were performed on all children including ferritin, iron and hepcidin. FIR was calculated and receiver operating characteristic curve analysis was performed to evaluate the best FIR cutoff value to discriminate between patients and controls and between patients with bacterial infections and viral infections. RESULTS: Hepcidin, ferritin and FIR were significantly higher and iron values significantly lower in febrile patients than its controls. Patients with bacterial infection had significantly lower iron and higher FIR than those with viral infection. FIR had high accuracy discriminating patients from controls but only moderate accuracy discriminating bacterial from viral infected patients. CONCLUSIONS: If further studies with larger samples confirm these observations, FIR could be used as an inexpensive, rapid and easily performed complementary index for diagnosis of bacterial infections.

Severe Eosinophilia in an infant with congenital acute myeloid leukemia with t(3;4;6)(q26;q25;q21): a case report.

SUMMARY: We report a case of acute myeloid leukemia with morphologic features of M7 according to the FAB (French-American-British) classification and severe eosinophilia in the peripheral blood and bone marrow at diagnosis. We consider it as congenital leukemia, as the symptoms started in the first month of life of the affected child. This case of leukemia is characterized by t(3;4;6)(q26;q25;q21) cytogenetic abnormality. The blasts in flow cytometry analysis expressed markers of megakaryocytic lineage along with expression of myeloperoxidase in 30% of them. This type of acute myelogenous leukemia with severe eosinophilia can be considered as a distinct clinicopathologic entity.