Ákos Gasparics

Background: The importance and etiology of meconium-stained amniotic fluid (MSAF) in preterm pregnancies are still poorly understood. Among other factors, intrauterine inflammation is proposed to be a pathophysiological change associated with MSAF. To study the extent of intrauterine inflammation, histological evaluation represents the “gold standard” of diagnostics. Objectives: To investigate the concomitant occurrence of MSAF and histological chorioamnionitis (HCA) and fetal inflammatory response (FIR). To investigate the incidence of short-term neonatal outcomes in preterm infants born from MSAF. Materials and methods: We conducted a single-center retrospective study in a tertiary neonatal intensive care unit between 2020 and 2022. 237 preterm infants born ≤ 32 weeks or with ≤1500 g birthweight were investigated. The group of infants born from MSAF was compared to the group of infants born from clear amniotic fluid (CAF). The variables measured were the following: HCA, FIR, maternal and fetal vascular malformations (MVM, FVM), maternal clinical and laboratory signs of chorioamnionitis (CA), early neonatal outcomes, neonatal white blood cell count (WBC) in the first day of life, and neonatal c-reactive protein (CRP) level on the second day of life. Histological evaluation of the placenta and the umbilical cord was based on the recommendation of the 2014 Amsterdam Placental Workshop Group Consensus Statement (APWGCS). Results: Out of 237 preterm infants (mean gestational age: 28.6 (95% CI: 28.2; 28.9) weeks, mean birth weight: 1165 (95% CI: 1110; 1218) grams), 22 were born from MSAF. There was no difference between the perinatal characteristics of the two groups. A higher incidence of HCA (54.5% vs. 32.6%; p: p: 30 mg/L) maternal CRP level (36.8% vs. 15.3%; p: 0.02) and elevated (>15 mg/L) neonatal CRP level (31.8% vs. 14.4%; p: 0.03) was detected in the MSAF group. Among neonatal complications, severe (Stage III/IV) intraventricular hemorrhage (IVH) had a higher incidence in the MSAF group (22.2% vs. 5.1%; p: 0.005). Conclusion: MSAF in preterm pregnancies is associated with a severe maternal and fetal inflammatory response in the placenta and the umbilical cord. MSAF is also accompanied by elevated systemic inflammatory parameters and a higher incidence of severe neonatal IVH as well.

Background: Minimizing the duration of mechanical ventilation is one of the most important therapeutic goals during the care of preterm infants at neonatal intensive care units (NICUs). The rate of extubation failure among preterm infants is between 16% and 40% worldwide. Numerous studies have been conducted on the assessment of extubation suitability, the optimal choice of respiratory support around extubation, and the effectiveness of medical interventions. Since the Caffeine Therapy for Apnea of Prematurity (CAP) trial, caffeine has become one of the essential drugs at NICUs. However, the optimal dosage and timing for adequate effectiveness still need to be more conclusive. Previous studies suggest that higher doses of caffeine treatment increase the success rate of extubation. Therefore, we aim to determine whether using a single additional loading dose of caffeine citrate one hour prior to extubation impacts the success rate of extubation. Methods: The study is an open-label, multicenter randomized clinical trial testing the effectiveness and safety of pre-extubational loading dose of caffeine citrate. Inclusion criteria will be infants born before the 32^nd gestational week, before the first extubation attempt after at least 48 hours of mechanical ventilation, and a signed parental informed consent. A total of 226 patients will be randomly allocated to either the experimental or control group. The randomization will be stratified by gestational age and antenatal steroid prophylaxis. Preterm infants in the experimental group will receive an additional intravenous (IV) loading dose (20 mg/kg) of caffeine citrate one hour before the first planned extubation, in addition to the standard dosing regimen (20 mg/kg caffeine citrate IV on the first day of life and 5 to 10 mg/kg IV or orally caffeine citrate each consecutive day). Preterm infants in the control group will receive the standard dosing regimen. The primary outcome will be reintubation within 48 hours. Discussion: A pre-extubational loading dose of caffeine citrate can reduce extubation failure. Obtaining evidence on this feature has the potential to contribute to finding the optimal dosing regimen. Trial registration number: The study protocol was approved by the Hungarian Ethics Committee for Clinical Pharmacology of the Medical Research Council and National Institute of Pharmacy and Nutrition (OGYÉI/6838-11/2023). ClinicalTrials.gov identifier NCT06401083 Registered 06. May 2024.; EudraCT number: 2022-003202-77.

Background: Evidence supporting the benefits of delayed cord clamping is increasing; however, there is no clear recommendation on cord management during newborn resuscitation. This study aimed to investigate the effects of resuscitation initiated with an intact umbilical cord, hypothesizing it is a safe stabilization procedure that improves neonatal outcomes. Methods: Systematic search was conducted in MEDLINE, Embase, CENTRAL, and Web of Science from inception to March 1, 2024. Eligible articles compared neonatal outcomes in newborns receiving initial stabilization steps before and after cord clamping. Results: Twelve studies met our inclusion criteria, with six RCTs included in the quantitative analysis. No statistically significant differences were found in delivery room parameters, in-hospital mortality, or neonatal outcomes between the examined groups. However, intact cord resuscitation group showed higher SpO₂ at 5 min after birth compared to cord clamping prior to resuscitation group (MD 6.67%, 95% CI [−1.16%, 14.50%]). There were no significant differences in early complications of prematurity (NEC ≥ stage 2: RR 2.05, 95% CI [0.34, 12.30], IVH: RR 1.25, 95% CI [0.77, 2.00]). Conclusion: Intact cord management during resuscitation appears to be a safe intervention; its effect on early complications of prematurity remains unclear. Further high-quality RCTs with larger patient numbers are urgently needed. Impact: Initiating resuscitation with an intact umbilical cord appears to be a safe intervention for newborns. No statistically significant differences were found in delivery room parameters, in-hospital mortality, and neonatal outcomes between the examined groups. The utilization of specialized resuscitation trolleys appears to be promising to reduce the risk of intraventricular hemorrhage in preterm infants. Further high-quality RCTs with larger sample sizes are urgently needed to refine recommendations.

Nowadays, whole-body vibration (WBV) has become increasingly popular as an additional therapy in the intervention of patients with cerebral palsy (CP). However, the impact of WBV remains a subject of debate. Consequently, a systematic review and meta-analysis were undertaken to evaluate the effects of WBV on the musculoskeletal system in children with CP. Randomized controlled trials (RCTs) were sought in the most frequent databases. The intervention studied was WBV combined with conventional physiotherapy (PT) compared with conventional PT as the control; the main outcomes were changes in the musculoskeletal system. Weighted mean differences with 95%CIs were calculated. A random-effects model was applied, and the publication bias was checked using funnel plots. On the basis of the inclusion and exclusion criteria, 16 articles, including 414 patients, were considered in the final analysis. The improvement in walking performance (speed and step length) was statistically significant (p < 0.05), and although there were no significant differences in the further outcomes, a clear positive tendency was visible in the case of improved muscle strength, decreased spasticity, enhanced gross motor functions, and overall stability. Based on the findings, a clear assessment of the usefulness of this intervention cannot be made; nonetheless, due to the promising results, it would be worthwhile to conduct additional RCTs to enhance the available evidence in this field. Due to the wide range of vibration configurations, including varying durations and intensities, it is suggested to establish guidelines and a strategy for the incorporation of this additional treatment.

Epithelial–mesenchymal transition (EMT) is a process of cellular plasticity regulated by complex signaling networks. Under physiological conditions, it plays an important role in wound healing and organ repair. Its importance for human disease is given by its central role in chronic fibroproliferative diseases and cancer, which represent leading causes of death worldwide. In tumors, EMT is involved in primary tumor growth, metastasis and therapy resistance. It is therefore a major requisite to investigate and understand the role of EMT and the mechanisms leading to EMT in order to tackle these diseases therapeutically. Forward genetic screens link genome modifications to phenotypes, and have been successfully employed to identify oncogenes, tumor suppressor genes and genes involved in metastasis or therapy resistance. In particular, transposon-based insertional mutagenesis screens and CRISPR-based screens are versatile and easy-to-use tools applied in recent years to discover and identify novel cancer-related mechanisms. Here, we review the contribution of forward genetic screens to our understanding of how EMT is regulated and how it is involved in various aspects of cancer. Based on the current literature, we propose these methods as additional tools to investigate EMT.

The limit of viability for premature newborns has changed in recent decades, but whether to initiate or withhold active care for periviable infants remains a subject of debate because the chances of survival and the extent of severe neurological impairment can be unclear. In our review, we analyzed large population-based studies of periviable infants from the past 2 decades. We compared survival rates and the incidence of early complications among survivors, including bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, and necrotizing enterocolitis. Moreover, we assessed the perinatal factors that may affect the survival of preterm infants. We analyzed 15 studies reporting data on preterm infants born between 22 and 28 gestational weeks. None of these studies reported survival of an infant born before 22 gestational weeks. Survival rates of infants born at 24 weeks’ gestation were above 50% in most studies. The incidence of each complication was also higher among infants born at ≤24 weeks. Of the analyzed perinatal factors, antenatal corticosteroid therapy, birth weight, female sex, cesarean delivery, singleton pregnancy, and birth in a tertiary-level Neonatal Intensive Care Unit were found to be associated with improved survival in some studies. The different methodologies of the studies limited comparison of the results. Further investigations are needed to gain up-to-date information on the limit of viability, and standardized methods in future studies would enable more accurate comparisons of findings.

Background There are limited data available on the survival and early complications of preterm infants with less than 500 g birthweight. To estimate the outcomes for these infants, it is important for caregivers to be aware of perinatal factors that may affect survival. Objectives We assessed the mortality and certain early complications of preterm infants born with less than 500 g in Hungary between 2006 and 2015. Methods We reviewed data of 486 infants from the database of the Hungarian Central Statistical Office and in parallel of 407 infants from the “NICU database.” The study period was divided into two epochs: 2006‐2010 and 2011‐2015. Results The survival was 27.1% in the first epoch and 39.1% in the second epoch, and the incidence of early complications was slightly higher in the second epoch. In the surviving group (first and second epoch combined), gestational age (25.1 vs 23.7 weeks), birthweight (458 vs 447 g) antenatal steroid treatment (66.3% vs 52.3%), surfactant therapy (95.1% vs 84.3%), median Apgar scores (6 vs 3 and 8 vs 5 at 1 and 5 minutes, respectively) and proportion of caesarean delivery (89.3% versus 68.5%) were higher than in the non‐surviving group (first and second epoch combined). The proportion of multiple births was lower in the surviving group (15.7% vs 33.4%). Conclusions Survival of infants with less than 500 g improved between 2006‐2010 and 2011‐2015 in Hungary. The slightly higher occurrence of early complications might be associated with improving survival.