D-dimer as a Useful Biomarker in Early Diagnosis of Neonatal Sepsis: A Single-Center Study From Romania.

BACKGROUND: This study evaluates the role of D-dimer in identifying neonatal sepsis and their potential value in clinical decision-making due to challenges in early detection. METHODOLOGY: A case-control study was conducted on 102 neonates at the Children's Clinical Hospital "Louis Turcanu" in Timisoara, Romania, from October 2018 to July 2023. The participants were divided into two groups: those with neonatal sepsis and those without sepsis. RESULTS: The study found that neonates with sepsis were more likely to be delivered by cesarean section and had higher rates of premature ruptured membranes compared to those without sepsis. The D-dimer biomarker's predictive value for sepsis was assessed using a receiver operating characteristic (ROC) curve, with an area under the curve (AUC) exceeding 0.982 and an optimum cutoff value of 342 ng/mL. An increase in neonatal D-dimer significantly increases the likelihood of sepsis by 2.7% per unit increase. A value above 250 ng/mL indicates a 127-fold increased likelihood of sepsis. The D-dimer's ability to predict mortality in newborns with sepsis is unsatisfactory, with an AUC of 0.528. CONCLUSIONS: D-dimer, a potential biomarker of neonatal sepsis, warrants further clinical investigation to enhance diagnostic sensitivity and specificity, demonstrating its potential in conjunction with other sepsis markers.

Predictive Value of Neutrophil-to-Monocyte Ratio, Lymphocyte-to-Monocyte Ratio, C-Reactive Protein, Procalcitonin, and Tumor Necrosis Factor Alpha for Neurological Complications in Mechanically Ventilated Neonates Born after 35 Weeks of Gestation.

This prospective study investigated the association between elevated neutrophil-to-monocyte ratio (NMR), lymphocyte-to-monocyte ratio (LMR), C-reactive protein (CRP), procalcitonin, and tumor necrosis factor-alpha (TNF-alpha) and the risk of developing neurological complications in mechanically ventilated neonates. The aim was to evaluate these biomarkers' predictive value for neurological complications. Within a one-year period from January to December 2022, this research encompassed neonates born at ≥35 weeks of gestational age who required mechanical ventilation in the neonatal intensive care unit (NICU) from the first day of life. Biomarkers were measured within the first 24 h and at 72 h. Sensitivity, specificity, and area under the curve (AUC) values were calculated for each biomarker to establish the best cutoff values for predicting neurological complications. The final analysis included a total of 85 newborns, of which 26 developed neurological complications and 59 without such complications. Among the studied biomarkers, TNF-alpha at >12.8 pg/mL in the first 24 h demonstrated the highest predictive value for neurological complications, with a sensitivity of 82%, specificity of 69%, and the highest AUC (0.574, p = 0.005). At 72 h, TNF-alpha levels greater than 14.3 pg/mL showed further increased predictive accuracy (sensitivity of 87%, specificity of 72%, AUC of 0.593, p < 0.001). The NMR also emerged as a significant predictor, with a cutoff value of >5.3 yielding a sensitivity of 78% and specificity of 67% (AUC of 0.562, p = 0.029) at 24 h, and a cutoff of >6.1 showing a sensitivity of 76% and specificity of 68% (AUC of 0.567, p = 0.025) at 72 h. Conversely, CRP and procalcitonin showed limited predictive value at both time points. This study identifies TNF-alpha and NMR as robust early predictors of neurological complications in mechanically ventilated neonates, underscoring their potential utility in guiding early intervention strategies. These findings highlight the importance of incorporating specific biomarker monitoring in the clinical management of at-risk neonates to mitigate the incidence of neurological complications.

Early Postnatal Administration of Erythropoietin and Its Association with Neurodevelopmental Outcomes and Incidence of Intraventricular Hemorrhage and Hypoxic-Ischemic Encephalopathy: A Four-Week Observational Study.

This study aimed to investigate the impact of early erythropoietin (EPO) administration on the neurodevelopment of newborns, specifically focusing on its effects on hypoxic-ischemic encephalopathy (HIE) and intraventricular hemorrhage (IVH). The primary objective was to determine whether early EPO administration could impact the short-term neurodevelopmental outcomes and provide safety in neonates at risk for neurodevelopmental disorders. Conducted at the "Louis Turcanu" Children's Emergency Clinical Hospital in Timisoara, Romania, this observational study included 121 neonates receiving EPO and 130 No EPO controls. EPO was administered within the first 48 h of life, with doses of 1000 U/kg that escalated to 2000 U/kg if necessary. Besides observing the occurrence of IVH and HIE, this study measured clinical and biochemical markers, including LDH, blood glucose, urea, creatinine, CPK, CRP, PCT, and erythropoietin levels alongside hematology and coagulation profiles. There were no significant differences in baseline characteristics between the groups. The EPO group showed significant reductions in LDH levels from days 1-3 to 7-10 (695.0 U/L to 442.0 U/L) and the APTT value (54.0 s) compared with the No EPO group (38.0 s). Notably, early EPO administration was associated with a significant decrease in HIE severity (beta coefficient: -0.38, p = 0.001). Additionally, lower gestational ages and hemoglobin levels correlated with increased severity of HIE. By week four, there was a significant reduction in moderate and severe HIE cases in the EPO group compared with controls (p = 0.001). Early administration of EPO in neonates significantly reduced the severity of IVH and HIE, suggesting its potential as a neuroprotective agent in neonatal care.

The Effects of Iron Administration on Anemia Development during the 7th and 21st Day of Life in Premature Newborns: A Prospective Cohort Study.

Background and Objectives: The administration of iron to premature newborns is a common intervention aimed at preventing iron deficiency (ID). However, there is no consensus on the optimal timing and dosage for iron supplementation in this population. This study evaluates the effects and potential adverse outcomes of administering iron on the 7th and 21st days of life in premature infants. Materials and Methods: This research was conducted on 108 premature neonates at the "Louis Turcanu" Children's Emergency Clinical Hospital in Timisoara, Romania. The study population was divided into a control group of 48 newborns who did not receive iron supplementation and an intervention group of 60 newborns who did. The analysis utilized univariate and multivariate regression to examine binary outcomes. Results: The findings indicate that iron supplementation significantly increased the risk of anemia during the premature period at 21 days of life, as demonstrated by both univariate and multivariate regression analyses, with an odds ratio (OR) of 2.40 (95% CI, 1.01-5.68) and an adjusted odds ratio (AOR) of 2.75 (95% CI, 1.06-7.11), respectively. Contrary to expectations, iron supplementation did not significantly alter the risk of abnormal serum ferritin or iron levels at 21 days of life, according to the univariate analysis (p = 0.380 and p = 0.526, respectively). Conclusions: The observed increase in the risk of anemia without a corresponding improvement in the serum ferritin or iron levels suggests the need for further investigation into alternative strategies for iron supplementation in premature newborns.

Hemoglobin, Ferritin, and Lactate Dehydrogenase as Predictive Markers for Neonatal Sepsis.

(1) Background: This study evaluates the predictive effectiveness of biomarkers in diagnosing newborn sepsis. (2) Methods: This was a case-control study conducted on neonates hospitalized at the Clinical Hospital "Louis Turcanu", Timisoara, Romania, from October 2018 to July 2023. Using a vacutainer collection device, venous blood was collected at admission for complete blood tests, including ferritin, hemoglobin, LDH, and blood culture analysis. Neonates were divided into two groups: sepsis-positive and sepsis-negative. The outcome of interest was a diagnosis of sepsis. (3) Results: Data from 86 neonates, 51 of whom had been confirmed to have sepsis, were analyzed. This study found no significant difference in gestational age, infant weight, fetal growth restriction, or APGAR score between neonates with and without sepsis. However, there was a higher incidence of sepsis among neonates delivered via cesarean section. Neonatal patients with sepsis showed significantly higher levels of neonatal serum ferritin and LDH compared to those without sepsis. Ferritin and LDH biomarkers demonstrated excellent discriminatory capabilities in diagnosing neonatal sepsis. Logistic regression analysis revealed a significant association between elevated ferritin and LDH levels and the likelihood of neonatal sepsis, while anemia did not show a significant association. (4) Conclusions: LDH and ferritin concentrations are found to be predictive biomarkers for neonatal sepsis, indicating a potential role in detecting susceptible neonates and implementing prompt interventions to improve patient outcomes.

Effect of Nasal Continuous Positive Airway Pressure on Retinopathy of Prematurity in Preterm Newborns: A Comparative Analysis with Mechanical Ventilation and High-Flow Nasal Cannula Therapy.

BACKGROUND Retinopathy of prematurity (ROP), originally described as retrolental fibroplasia, represents an abnormal growth of blood vessels in the premature retina that can occur in response to oxygen therapy. The association between ROP and invasive mechanical ventilation has been widely studied in the literature; however, the relationships between different types of ventilation and ROP have not been as well documented. This study aimed to compare the association of ROP incidence with mechanical ventilation (MV), nasal continuous positive airway pressure (nCPAP), and high-flow nasal cannula (HFNC) therapies in 130 pre-term infants with gestational ages <32 weeks. MATERIAL AND METHODS The study includes 130 premature newborns, out of which 54 underwent MV therapy, either alone or in combination with nCPAP or HFNC therapy, 63 underwent nCPAP therapy, either alone or in combination with MV or HFNC therapy, and 23 underwent HFNC therapy, either alone or in combination with MV or nCPAP therapy. The relationships between ROP and the 3 types of ventilation were analyzed by univariate followed by multivariate logistic regression. RESULTS When adjusting for covariates, only nCPAP and birth weight were significantly associated with ROP, the former being a strong risk factor, with an adjusted odds ratio (AOR) of 7.264 (95% CI, 2.622-20.120; P<0.001), and the latter being a weak protective factor, with an AOR of 0.998 (95% CI, 0.996-0.999; P<0.05). CONCLUSIONS The results showed nCPAP was a strong ROP risk factor, birth weight was a weak ROP protective factor, and MV and HFNC were not significantly associated with increased ROP risk.

The Role of Erythropoietin in Preventing Anemia in the Premature Neonate.

Recombinant human erythropoietin (rhEPO) treatment is an alternative to red blood cell (RBC) transfusions in neonates presenting anemia of prematurity (AOP). This study assesses the impact of early rhEPO administration on AOP (any stage) incidence, as well as the incidence of individual AOP stages and RBC transfusions. Out of 108 preterm neonates, 49 were administered rhEPO and compared to the remaining group using univariate and multivariate analyses. Univariately, gestational age (GA), birth weight (BW), hemoglobin (Hb), hematocrit (HCT), RBC levels, and iron administration were significantly associated with AOP (p < 0.05 each); however, only the latter remained significant following multivariate analysis (AOR: 2.75, 95% CI, 1.06-7.11). Multinomial analysis revealed rhEPO treatment was associated with a near three-fold reduction in moderate AOP incidence (OR: 0.36, 95% CI, 0.15-0.89). Furthermore, ANCOVA revealed positive correlations between rhEPO administration and 21-day Hb (p < 0.01), HCT (p < 0.05), and EPO (p < 0.001) levels. The results confirm previously reported benefits of rhEPO treatment, such as reduced moderate AOP incidence and increased Hb, HCT, and serum EPO levels.

Does COVID-19 Infection during Pregnancy Increase the Appearance of Congenital Gastrointestinal Malformations in Neonates?

BACKGROUND: COVID-19 was an infection that was capable of bringing the entire world to a standstill position within a period of days to months. Despite the advancements in the medical sector, the contagion was difficult to control and costed the lives of millions of people worldwide. Many short- and long-term effects are witnessed even to date in people that contracted the disease. Pregnant females had to suffer not only the devastating effects of the virus, but also the psycho-social impact of the lockdown. The impact of COVID-19 infection during pregnancy causing decreased antenatal care or hypoxemic episodes due to severe respiratory distress and whether it could lead to the appearance of congenital gastrointestinal malformation in neonates is still unclear. The aim of our study was to analyze if COVID-19 infection during pregnancy could increase the incidence of gastric malformations in neonates born from these women. MATERIALS AND METHODS: We sifted the files of all neonates admitted into our hospital between January 2022 and December 2022, and based on inclusion and exclusion criteria, we included the cases having gastrointestinal congenital malformations during the COVID-19 pandemic. We performed a single-center, retrospective, observational descriptive study. We further divided the patients based on the anatomical location of the malformation. We also took down details of the evolution of pregnancy and whether the mother had contracted a SARS-CoV-2 infection during the pregnancy. Details regarding the Apgar score, days of intensive care admission, sex, and nutrition were the key findings studied. RESULTS: A total of 47 neonates were found to have digestive anomalies, among which, based on the anatomical locations, the number of malformation cases found at the level of the esophagus were 15, while 16 occurred at the level of the pylorus; we found 12 cases of malformation of the duodenum, and four cases had malformation of the rectum. Out of these 47 neonates, 38.3% were females and 61.7% were males. A total of 58% were preemies, among which 9% had intra-uterine growth retardation (IUGR), and 42% were full-term newborns, among which 4% had intra-uterine growth retardation (IUGR). A total of 45% of the births were primiparous pregnancies and 55% were from multiparous females. A total of 14 mothers were found to have tested positive for COVID-19 during the course of pregnancy (p-value = 0.23); many had mild symptoms but were not tested. CONCLUSIONS: COVID-19 can affect the wellbeing of the pregnant female and their fetus. Larger studies can help gain extensive knowledge as to whether COVID-19 also has the potential to result in congenital gastrointestinal anomalies in children born from COVID-19 positive mothers. In our study, only a few infants born with this pathology were found to be born from COVID-19 positive mothers. Hence, it is difficult to conclude or exclude a direct correlation between the infection and the congenital malformations.

The Neutrophil-to-Lymphocyte Ratio (NLR) Can Predict Sepsis's Presence and Severity in Malnourished Infants-A Single Center Experience.

Sepsis represents one of the leading causes of death in newborns and infants, and prompt diagnosis is essential for achieving favorable outcomes. Regarding malnourished children with concurrent infection, most studies have focused, besides blood culture, on C-reactive protein and procalcitonin. Because malnutrition has a deleterious effect on cellular immune competence, the present study characterized the acute-phase response, including hematological indices, in response to sepsis. Among the examined laboratory biomarkers, procalcitonin and neutrophil-to-lymphocyte ratio were the most accurate discriminators between sepsis patients and those with bacterial infection. Moreover, these two parameters showed a gradual increase between sepsis, severe sepsis, and septic shock patients (p < 0.001). Subgroup analysis of the sepsis group revealed positive correlations of NLR with prolonged ICU stay (<0.001), acute organ dysfunction (0.038), mechanical ventilation (<0.001), and fatality (<0.001). In summary, our results suggest that the neutrophil-to-lymphocyte ratio can be used as an auxiliary diagnostic index in discriminating the presence and severity of bacterial sepsis in malnourished infants.

Comparative Analysis of Hematological and Biochemical Changes in Neonates among Women with and without COVID-19 Infection during Pregnancy.

The aim of this study is to evaluate the test results of neonates delivered by COVID-19-positive mothers during pregnancy with those of neonates born to unvaccinated mothers who are COVID-19-free. A cohort study was conducted on 367 pregnant women who gave birth at Premiere Hospital, Timisoara, Romania, between May 2021 and February 2022. Two groups were established: Group 1, with 167 pregnant women infected with COVID-19, and Group 2, with 200 pregnant women who were not affected by COVID-19 during pregnancy. Maternal laboratory examination did not exhibit significant variations except for platelet count. In neonatal blood tests, WBC had a significantly lower median value in the group born to COVID-19-free mothers. Neonatal anemia and leukocytosis showed slightly higher prevalence in Group 1, but the differences were not statistically significant. This study suggests that maternal COVID-19 infection during pregnancy does not have significant associations with most maternal and neonatal characteristics.

The Role of Amplitude-Integrated Electroencephalography (aEEG) in Monitoring Infants with Neonatal Seizures and Predicting Their Neurodevelopmental Outcome.

Newborn monitoring in neonatal intensive care units (NICU) is mandatory, but neurological and especially electroencephalographic (EEG) monitoring can be overlooked or delayed until the newborn is clinically stable. However, the neonatal period is associated with the highest risk of seizures in humans, and the clinical symptoms may often be discrete, but the evolution and long-term neurodevelopmental disorders in these patients may be important. In response to this issue, we conducted a study to evaluate newborns who experienced neonatal seizures (NS) in the NICU and monitored their long-term neurological development. We enrolled 73 term and preterm newborns who underwent EEG monitoring using amplitude-integrated electroencephalography (aEEG). We then followed their neurological development until around 18 months of age, with 59 patients remaining in the long-term study. A total of 22% of patients with NS developed epilepsy, 12% cerebral palsy, 19% severe neurodevelopmental disabilities, and 8.5% died within the first 18 months of life. Our findings indicate that aEEG background pattern is a strong predictor of unfavorable neurological outcomes, with an odds ratio of 20.4174 (p < 0.05). Additionally, higher Apgar scores were associated with better outcomes (p < 0.05), with the odds of unfavorable neurological outcomes decreasing by 0.7-fold for every point increase in Apgar score. Furthermore, we found a statistically significant association between preterm birth and unfavorable neurological outcomes (p = 0.0104). Our study highlights the importance of early EEG monitoring in the NICU and provides valuable insights into predictors of unfavorable neurological outcomes in newborns who experienced NS.

Macronutrients Management for Growth in Neonates with Congenital Gastrointestinal Malformation.

BACKGROUND Congenital gastrointestinal (GI) malformations are developmental disorders that can result in secondary intestinal failure. Nutrient intakes must be adapted according to the newborn's nutritional requirements based on frequent anthropometric and biochemical assessments. Deficiencies or excess of a macronutrient can hinder the growth of the newborn. MATERIAL AND METHODS To assess the clinical condition of newborns with GI malformations, together with the postoperative nutritional status of newborns who underwent surgery due to congenital GI malformations, we performed a case-control study. The study group comprised newborns with digestive malformations (n=51) and the control group consisted of newborns without digestive pathologies (n=102), matched by sex, gestational age, and weight at admission. RESULTS Bivariate comparisons and multiple logistic regression analyses were performed. A P value <0.05 was considered to be statistically significant; these were observed in abdominal distension, gastric residue, and vomiting. The duration of hospitalization was shorter in the case group, as on average, they were transferred to the Pediatric Surgery Department on the 6th day, where they further remained admitted to treat the underlying cause. Differences between groups in administration of breast milk versus formula were not statistically significant. CONCLUSIONS We concluded that the clinical examination had a major role in early detection of digestive malformations and in the effective management of specific necessary nutrition. Proper evaluation of when to start enteral feeding can help post-surgical cases to recover faster, minimizing complications. Further studies are required to assess how financial factors affect implementation of the standardized guidelines of nutrition in children and to find possible solutions to financial constraints.

In Vitro Toxicological Profile of Labetalol-Folic Acid/Folate Co-Administration in H9c2(2-1) and HepaRG Cells.

Background and Objectives: The consumption of dietary supplements has increased over the last decades among pregnant women, becoming an efficient resource of micronutrients able to satisfy their nutritional needs during pregnancy. Furthermore, gestational drug administration might be necessary to treat several pregnancy complications such as hypertension. Folic acid (FA) and folate (FT) supplementation is highly recommended by clinicians during pregnancy, especially for preventing neural tube birth defects, while labetalol (LB) is a ß-blocker commonly administered as a safe option for the treatment of pregnancy-related hypertension. Currently, the possible toxicity resulting from the co-administration of FA/FT and LB has not been fully evaluated. In light of these considerations, the current study was aimed at investigating the possible in vitro cardio- and hepato-toxicity of LB-FA and LB-FT associations. Materials and Methods: Five different concentrations of LB, FA, FT, and their combination were used in myoblasts and hepatocytes in order to assess cell viability, cell morphology, and wound regeneration. Results: The results indicate no significant alterations in terms of cell viability and morphology in myoblasts (H9c2(2-1)) and hepatocytes (HepaRG) following a 72-h treatment, apart from a decrease in the percentage of viable H9c2(2-1) cells (~67%) treated with LB 150 nM−FT 50 nM. Additionally, LB (50 and 150 nM)−FA (0.2 nM) exerted an efficient wound regenerating potential in H9c2(2-1) myoblasts (wound healing rates were >80%, compared to the control at 66%), while LB-FT (at all tested concentrations) induced no significant impairment to their migration. Conclusions: Overall, our findings indicate that LB-FA and LB-FT combinations lack cytotoxicity in vitro. Moreover, beneficial effects were noticed on H9c2(2-1) cell viability and migration from LB-FA/FT administration, which should be further explored.

In Vitro and In Ovo Evaluation of the Potential Hepatoprotective Effect of Metformin.

Background and Objectives: Metformin is currently the leading drug of choice for treating type 2 diabetes mellitus, being one of the most widely used drugs worldwide. The beneficial effects of Metformin, however, extend far beyond the reduction of blood glucose. Therefore, this study aimed to evaluate Metformin's effects both in vitro and in ovo. Materials and Methods: Metformin has been tested in five different concentrations in human hepatocytes -HepaRG, in terms of cell viability, morphology, structure and number of nuclei and mitochondria, as well as the effect on cell migration. Through the application of HET-CAM, the biocompatibility and potential anti-irritant, as well as protective effects on the vascular plexus were also assessed. Results: According to the results obtained, Metformin increases cell viability without causing morphological changes to cells, mitochondria, or nuclei. Metformin displayed an anti-irritant activity rather than causing irritation at the level of the vascular plexus. Conclusions: In conclusion, Metformin enhances cell viability and proliferation and, has a protective effect on the vascular plexus. Nonetheless, more studies are required to clarify the mechanism of hepatoprotective effect of metformin.

Clinical Factors Associated with COVID-19 Severity in Chronic Hospitalized Infants and Toddlers: Data from a Center in the West Part of Romania.

BACKGROUND: The risk factors for developing a severe form of COVID-19 in young children are poorly understood. METHODS: A single-center retrospective study was conducted to quantify and analyze the clinical risk profile of children admitted to the Pediatric Clinic for Nutritional Recovery. RESULTS: Overall, 51.5% (n = 17) of children were infected with SARS-CoV-2, all symptomatic, and five of them (29.4%) developed a severe form. A positive clinical pulmonary exam was only associated with the severe outcome (OR: 2.00; 95% CI, 0.33-5.66; p = 0.02). Other factors such as age under 3 months, prematurity, birth weight, malnutrition or positive history of congenital cardiac, neurodevelopmental, or genetic diseases, fever, temperature, cough, and digestive symptoms were not found to be significant risk factors. CONCLUSIONS: Clinical guidelines based on risk stratification for SARS-CoV-2 infection in children are needed in order to manage, monitor and establish priority access for some groups to high medical care.

Lung Ultrasound in Children with Cystic Fibrosis in Comparison with Chest Computed Tomography: A Feasibility Study.

BACKGROUND: Cystic fibrosis (CF) lung disease determines the outcome of this condition. For lung evaluation processes, computed tomography (CT) is the gold standard, but also causes irradiation. Lately, lung ultrasound (LUS) has proven to be reliable for the diagnosis of consolidations, atelectasis, and/or bronchiectasis. The aim of our study was to evaluate the value of a newly conceived LUS score by comparing it to the modified Bhalla CT score. A further aim was to evaluate the correlation between the score and the lung clearance index (LCI). METHODS: Patients with CF were screened by LUS, followed by a CT scan. Spearman's test was used for correlations. RESULTS: A total of 98 patients with CF were screened, and 57 were included in the study; their mean age was 11.8 ± 5.5 (mean ± SD) years. The mean LUS score was 5.88 ± 5.4 SD. The LUS CF score had a very strong correlation with the CT score of rs = 0.87 (p = 0.000). LUS showed a good sensibility for detecting atelectasis (Se = 83.7%) and consolidations (Se = 94.4%). A lower Se (77.7%) and Sp (9%) were found for cylindrical bronchiectasis. CONCLUSION: Our study shows that LUS and the lung CF score are parameters that can be used with a complementary role in the diagnosis and monitoring of CF lung disease in children.

Methotrexate and Cetuximab-Biological Impact on Non-Tumorigenic Models: In Vitro and In Ovo Assessments.

Background Objectives: The neoplastic process remains a major health problem facing humanity. Although there are currently different therapeutic options, they raise a multitude of shortcomings related to the toxic effects associated with their administration. Methotrexate (Met) and Cetuximab (Cet) are two basic chemotherapeutics used in cancer practice, but notwithstanding despite many years of use, the mechanisms by which the multitude of side-effects occur are not yet fully understood. Thus, the present study focused on the in vitro and in ovo evaluation of the associated toxic mechanisms on keratinocytes, keys cells in the wound healing process. Materials and Methods: The two chemotherapeutics were tested in eight different concentrations to evaluate keratinocytes viability, the anti-migratory effect, and the influence on the expression of markers involved in the production of cell apoptosis. In addition, the potential irritating effect on the vascular plexus were highlighted by applying the in ovo method, chick chorioallantoic membrane (HET-CAM). Results: The results revealed that Met induced decreased cell viability as well as increased expression of pro-apoptotic genes. In the vascular plexus of the chorioallantoic membrane, Met caused vascular irritation accompanied by capillary hemorrhage and vascular stasis. Conclusions: Summarizing, Cet presents a safer toxicological profile, compared to Met, based on the results obtained from both in vitro (cell viability, wound healing, RT-PCR assays), and in ovo (HET-CAM assay) techniques.

The "Invisible Enemy" SARS-CoV-2: Viral Spread and Drug Treatment.

Nowadays, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become the main subject of the scientific medical world and all World Organizations, causing millions of deaths worldwide. In this review, we have highlighted the context of the Coronavirus disease 2019 (COVID-19) pandemic, how the virus spreads, the symptoms and complications that may occur, and, especially, the drug treatment of viral infection, with emphasis on monoclonal antibodies. While well-known strains such as Alpha, Beta, Gamma, and, especially, Delta have shown an accelerated transmission among the population, the new Omicron variant (discovered on 24 November 2021) indicates more significant infectiousness and the poor efficacy of monoclonal antibody therapy due to mutations on the spike protein receptor-binding domain. With these discoveries, the experiments began, the first being in silico and in vitro, but these are not enough, and in vivo experiments are needed to see exactly the cause of neutralization of the action of these drugs. Following the documentation of the latest medical and scientific research, it has been concluded that there are many chemical molecules that have the potential to treat SARS-CoV-2 infection, but more detailed clinical trials are needed for their use in therapy. In addition, it is important to consider the structure of the viral strain in the administration of treatment.

Comparative Evaluation of the Potential Antitumor of Helleborus purpurascens in Skin and Breast Cancer.

In the field of oncology, the plant kingdom has an inexhaustible supply of bioactive compounds. Phytochemical compounds isolated from Helleborus species have been found to be useful in various chronic diseases. This has brought Helleborus to the attention of medical researchers. H. purpurascens is a plant characteristic of the Carpathian area, known since ancient times for its beneficial effects. The aim of the study was to evaluate the flavonoids composition of a hydroalcoholic extract of H. purpurascens, as well as to assess its antioxidant activity and antitumor potential at the level of two healthy cell lines and four tumor cell lines. In addition, the expression of the genes involved in the apoptotic process (Bcl-2, Bad, and Bax) were evaluated. The results indicated that the extract has a high concentration of flavonoids, such as epicatechin, quercetin, and kaempferol. The extract has an increased antioxidant activity, very similar to that of the standard, ascorbic acid and cytotoxic effects predominantly in the breast cancer cell line, being free of cytotoxic effects in healthy cell lines. Underlying the cytotoxic effect is the induction of the process of apoptosis, which in the present study was highlighted by decreasing the expression of anti-apoptotic genes (Bcl-2) and increasing the expression of pro-apoptotic genes (Bad and Bax). In conclusion, the hydroalcoholic extract of H. purpurascens can be considered an important source for future medical applications in cancer therapy.

Clinical, biological and electroencephalographic monitoring of newborns with neurological risk in the Neonatal Intensive Care Unit.

Newborns admitted to the Neonatal Intensive Care Unit (NICU) require increased attention regarding neurological assessment and monitoring, due to immaturity or certain conditions that occur during the perinatal and neonatal period. Hypoxic-ischemic encephalopathy (HIE) following perinatal asphyxia is one of the most studied clinical conditions due to the risk of medium- and long-term neurobehavioral outcome. We studied 43 newborns with HIE, for all 3 degrees of impairment, performed amplitude-integrated electroencephalography (aEEG) in the first hours of life and collected common laboratory tests, following serum glycemia at admission and creatinine, creatine kinase (CK) and lactate dehydrogenase (LDH) at admission and in the 3rd day of life. Newborns with mild HIE presented normal aEEG pattern and slightly elevated CK. A total of 80.9% of the newborns with moderate HIE had seizure patterns in aEEG, while among those with severe HIE, 71.4% had seizure patterns in aEEG and 28.5% burst suppression. CK and LDH were mean elevated in those with moderate HIE, and the newborns with severe HIE had also high creatinine values at admission and in the 3rd day of life. Statistically significant differences between the 3 degrees of HIE were noted in terms of creatinine (P=0.009) and CK (P=0.008) at admission and LDH in the 3rd day of life (P=0.036). Hypoglycemia was common in our study group. In conclusion, common blood tests in association with aEEG monitoring and rigorous neurological assessment can predict short-term outcome of HIE and multiorgan dysfunction and can help clinicians predict even long-term outcomes in severe HIE.