Mathematical model to predict methotrexate elimination in children with acute lymphoblastic leukemia

Introducere: Metotrexatul, analog structural al acidului folic, este unul dintre cel mai frecvent folosiți antimetaboliți în patologia oncologică pediatrică. Modul de acţiune și efectele toxice sunt bine cunoscute în prezent. Material şi metoda: Studiul realizat și-a propus să determine profilul eliminării metotrexatului la 40 copii cu leucemie limfatică acută trataţi cu doze mari din acest produs şi să prezică nivelul seric al metotrexatului la 96 ore în funcţie de valorile metotrexatemiei la 48h, 72h, respectiv valorile alaninaminotransferazei ALT, aspartataminotransferazei AST, ale ureei şi creatininei serice. Parametrii menţionaţi au fost analizaţi în probe recoltate la 48, 72 şi 96 ore după administrarea metotrexatului și pe baza rezultatelor obţinute elaborându-se un model de regresie logică. Rezultate şi concluzii: Valoarea metotrexatemiei serice la 96 ore nu depinde de nici una dintre valorile AST, ALT, uree, creatinină, nici de valoarea metotrexatemiei la 48 ore, ci doar de cea înregistrată la 72 ore

Genetic Modifying Factors of Cystic Fibrosis Phenotype: A Challenge for Modern Medicine

Cystic fibrosis (CF) is a monogenic autosomal recessive disease caused by cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations. CF is characterized by a high phenotypic variability present even in patients with the same genotype. This is due to the intervention of modifier genes that interact with both the CFTR gene and environmental factors. The purpose of this review is to highlight the role of non-CFTR genetic factors (modifier genes) that contribute to phenotypic variability in CF. We analyzed literature data starting with candidate gene studies and continuing with extensive studies, such as genome-wide association studies (GWAS) and whole exome sequencing (WES). The results of both types of studies revealed that the number of modifier genes in CF patients is impressive. Their identification offers a new perspective on the pathophysiological mechanisms of the disease, paving the way for the understanding of other genetic disorders. In conclusion, in the future, genetic analysis, such as GWAS and WES, should be performed routinely. A challenge for future research is to integrate their results in the process of developing new classes of drugs, with a goal to improve the prognosis, increase life expectancy, and enhance quality of life among CF patients

The Genetic Architecture of the Etiology of Lower Extremity Peripheral Artery Disease: Current Knowledge and Future Challenges in the Era of Genomic Medicine

Lower extremity artery disease (LEAD), caused by atherosclerotic obstruction of the arteries of the lower limb extremities, has exhibited an increase in mortality and morbidity worldwide. The phenotypic variability of LEAD is correlated with its complex, multifactorial etiology. In addition to traditional risk factors, it has been shown that the interaction between genetic factors (epistasis) or between genes and the environment potentially have an independent role in the development and progression of LEAD. In recent years, progress has been made in identifying genetic variants associated with LEAD, by Genome-Wide Association Studies (GWAS), Whole Exome Sequencing (WES) studies, and epigenetic profiling. The aim of this review is to present the current knowledge about the genetic factors involved in the etiopathogenic mechanisms of LEAD, as well as possible directions for future research. We analyzed data from the literature, starting with candidate gene-based association studies, and then continuing with extensive association studies, such as GWAS and WES. The results of these studies showed that the genetic architecture of LEAD is extremely heterogeneous. In the future, the identification of new genetic factors will allow for the development of targeted molecular therapies, and the use of polygenic risk scores (PRS) to identify individuals at an increased risk of LEAD will allow for early prophylactic measures and personalized therapy to improve their prognosis

Statistical Analysis of the Main Risk Factors of an Unfavorable Evolution in Gastroschisis

Gastroschisis is a congenital abdominal wall defect that presents an increasing occurrence at great cost for the health system. The aim of the study is to detect the main factors of an unfavorable evolution in the case of gastroschisis and to find the best predictors of death. Methods: we conducted a retrospective cohort study of neonates with gastroschisis treated in a tertiary pediatric center during the last 30 years; 159 patients were eligible for the study. Logistic regression was used to determine the risk of death, estimated based on independent variables previously validated by the chi-square test. Results: if the birth weight is below normal, then we find an increased risk (4.908 times) of evolution to death. Similarly, the risk of death is 7.782 times higher in the case of developing abdominal compartment syndrome, about 3 times in the case of sepsis and 7.883 times in the case of bronchopneumonia. All four independent variables contributed 47.6% to the risk of death. Conclusion: although in the past 30 years in our country we have seen transformational improvements in outcome of gastroschisis, survival rates increasing from 26% to 52%, some factors may still be ameliorated for a better outcome

An Up-to-Date Literature Review on Ventricular Assist Devices Experience in Pediatric Hearts

Ventricular assist devices (VAD) have gained popularity in the pediatric population during recent years, as more and more children require a heart transplant due to improved palliation methods, allowing congenital heart defect patients and children with cardiomyopathies to live longer. Eventually, these children may require heart transplantation, and ventricular assist devices provide a bridge to transplantation in these cases. The FDA has so far approved two types of device: pulsatile and continuous flow (non-pulsatile), which can be axial and centrifugal. Potential eligible studies were searched in three databases: Medline, Embase, and ScienceDirect. Our endeavor retrieved 16 eligible studies focusing on five ventricular assist devices in children. We critically reviewed ventricular assist devices approved for pediatric use in terms of implant indication, main adverse effects, and outcomes. The main adverse effects associated with these devices have been noted to be thromboembolism, infection, bleeding, and hemolysis. However, utilizing left VAD early on, before end-organ dysfunction and deterioration of heart function, may give the patient enough time to recuperate before considering a more long-term solution for ventricular support

The Genetic Architecture of Vascular Anomalies: Current Data and Future Therapeutic Perspectives Correlated with Molecular Mechanisms

Vascular anomalies (VAs) are morphogenesis defects of the vascular system (arteries, capillaries, veins, lymphatic vessels) singularly or in complex combinations, sometimes with a severe impact on the quality of life. The progress made in recent years with the identification of the key molecular pathways (PI3K/AKT/mTOR and RAS/BRAF/MAPK/ERK) and the gene mutations that lead to the appearance of VAs has allowed the deciphering of their complex genetic architecture. Understanding these mechanisms is critical both for the correct definition of the phenotype and classification of VAs, as well as for the initiation of an optimal therapy and the development of new targeted therapies. The purpose of this review is to present in synthesis the current data related to the genetic factors involved in the etiology of VAs, as well as the possible directions for future research. We analyzed the data from the literature related to VAs, using databases (Google Scholar, PubMed, MEDLINE, OMIM, MedGen, Orphanet) and ClinicalTrials.gov. The obtained results revealed that the phenotypic variability of VAs is correlated with genetic heterogeneity. The identification of new genetic factors and the molecular mechanisms in which they intervene, will allow the development of modern therapies that act targeted as a personalized therapy. We emphasize the importance of the geneticist in the diagnosis and treatment of VAs, as part of a multidisciplinary team involved in the management of VAs

Cardiac Biomarkers in Sports Cardiology

Sustained physical activity induces morphological and functional changes in the cardiovascular system. While mostly physiological, they can also become a trigger for major adverse cardiovascular events, the most severe of which are sudden cardiac arrest and sudden cardiac death. Therefore, any novel method which can help more accurately estimate the cardiovascular risk should be considered for further studying and future implementation in the standard protocols. The study of biomarkers is gaining more and more ground as they have already established their utility in diagnosing ischemic cardiac disease or in evaluating cardiac dysfunction in patients with heart failure. Nowadays, they are being implemented in the screening of apparently healthy individuals for the assessment of the cardiovascular risk. The aim of this paper is to gather published data regarding the measurements of cardiac biomarkers in athletes, i.e., troponins, myoglobin, CK-MB, NT-proBNP, and D-Dimers, and their potential use in the field of sports cardiology