ARGONAUTE-2 and associated miRNAs form the RNA-induced silencing complex (RISC), which targets mRNAs for translational silencing and degradation as part of the RNA interference pathway. Despite the essential nature of this process for cellular function, there is little information on the role of RISC components in human development and organ function. We identify 13 heterozygous mutations in AGO2 in 21 patients affected by disturbances in neurological development. Each of the identified single amino acid mutations result in impaired shRNA-mediated silencing. We observe either impaired RISC formation or increased binding of AGO2 to mRNA targets as mutation specific functional consequences. The latter is supported by decreased phosphorylation of a C-terminal serine cluster involved in mRNA target release, increased formation of dendritic P-bodies in neurons and global transcriptome alterations in patient-derived primary fibroblasts. Our data emphasize the importance of gene expression regulation through the dynamic AGO2-RNA association for human neuronal development.

Background: One of the frequently used methods for assessing research trends and the impact of published scientific literature in a particular discipline is citation analysis. Journals may strive to improve their metrics by choosing manuscripts and study designs that are more likely to be cited. The aim of this study was to identify the 50 most-cited articles in the field of pediatrics, analyze their study design and other characteristics of those articles, and assess the prevalence of systematic reviews among them.Methods: In December 2017, we searched Web of Science (WoS) for all articles published in the field of pediatrics. Two authors screened articles independently and in the further analysis included 50 articles with the highest number of citations. To avoid bias for scientific papers published earlier, the citation density was calculated. We also analyzed Journal Impact Factor (JIF) of journals where citation classics were published.Results: The citation density in top 50 cited articles in the field of pediatrics ranged from 33.16 to 432.8, with the average of 119.95. Most of the articles reported clinical science. Median 2016 JIF for journals that published them was 6.226 (range: 2.778 to 72.406). Half of the top 10 highly cited articles in pediatrics were published in a journal with JIF below 5. Most of the studies among the citation classics in pediatrics were cross-sectional studies (N = 22), followed by non-systematic narrative reviews (N = 10), randomized controlled trials (N = 5), cohort studies (N = 5), systematic reviews (N = 2), case-control studies (N = 2), case reports (N = 2), and there was one study protocol and one expert opinion.Conclusion: Few randomized controlled trials and systematic reviews were among citation classics in the field of pediatrics. Articles that use observational research methodology, and are published in journals with lower impact factors, can become citation classics.

Background and Objectives: When the human body is disabled to naturally ingest food through the mouth, enteral or parenteral nutritional support should be started. Percutaneous gastrostomy (PEG) is a flexible feeding tube that is inserted into the stomach through the abdominal wall in patients who will need long-term enteral nutrient intake. The aim of this study is to analyze clinical characteristic of children at the time of PEG placement as well as to determine indications, complications and outcomes associated with PEG at the Department of Pediatrics of the University Hospital of Split. Materials and Methods: Retrospective analysis of the medical records of patients treated from 2010 to 2020 was performed. The following data were collected from medical records: age, gender, information about nasogastric feeding before PEG placement, indication for PEG insertion, duration of PEG, procedure-related complications and treatment outcomes. Malnutrition was determined according to the z-score range for BMI for age and sex. According to the indication for PEG placement, patients were divided into five categories: central nervous system (CNS) diseases, neuromuscular diseases, genetic disorders, metabolic diseases, and group of children with polytrauma. Results: A total of 40 patients with median age of 110 months were included in study. At the time of PEG placement, most patients had deviations in body weight and height compared to expected values for age and sex. The most common underlying diagnoses were diseases of the central nervous system. Minor complications were found in 13 (35%) of patients. One patient (2.7%) developed major complication (gastrocolic fistula) and consequently underwent reoperation. The median duration of PEG in patients with complications before the need for replacement was 27 months, and in patients without complications, 43 months. Conclusions: Negative deviations of z-score body weight, body height, and body mass index could indicate the need for possible earlier placement of PEG. PEG can be considered as a safe therapeutic option in children since PEG-related complications, mostly in minor forms, were found in a small number of patients.

Background and objective: There is an increasing risk of type 1 diabetes mellitus (T1D) among children in Croatia. Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with T1D, with cerebral edema as the most severe complication. Since early recognition of cerebral edema leads to a better outcome, it is important that patients with moderate or severe DKA are closely monitored and treated in pediatric intensive care units (PICUs). The aim of this study is to investigate clinical and laboratory parameters, as well as complications in children treated in PICUs because of DKA. Materials and methods: Patients treated due to DKA in the PICU of the University Hospitals of Split and Osijek from 2013 to 2017 were included in this study. Retrospectively collected data included age, gender, clinical signs and symptoms, and various laboratory parameters. After dividing subjects into two groups: Newly diagnosed with T1D (NT1D) and previously diagnosed with T1D (PT1D), collected data were compared between the two groups. Results: A total of 82 patients were enrolled. Those with NT1D were more often treated in the PICU, with two of them developing cerebral edema. Dehydration was the most frequent clinical sign, found in 95% of patients at admission. Decreased consciousness level was found in 41.5% of patients, with majority of them being somnolent. No difference was found between NT1D and PT1D. Additionally, there was no significant difference regarding laboratory data at admission. Conclusions: More children with NT1D required treatment in the PICU due to DKA with two of them developing cerebral edema. Since cerebral edema is a life-threatening condition, treatment of patients with moderate or severe DKA in PICUs will provide necessary monitoring enabling early recognition, treatment, and better treatment outcome. To minimize the incidence of DKA among patients with NT1D, it is important to continuously carry out public health education programs aimed at early identification of signs and symptoms of T1D.

Natural cardiac glycosides have positive inotropic heart effects but at high, toxic doses they can cause life-threatening cardiac arrhythmias. Here we present the first Croatian case of a 16-year-old girl who attempted suicide by eating dried oleander leaves, which contain natural cardiac glycosides, and her treatment with a specific antidote. The girl presented with an oedema of the uvula indicating local toxicity, severe bradycardia, first-degree atrioventricular block, drowsiness, and vomiting. Having taken her medical history, we started treatment with atropine, intravenous infusion of dextrose-saline solution and gastroprotection, but it was not successful. Then we introduced digoxin-specific Fab antibody fragments and within two hours, the patient's sinus rhythm returned to normal. Cases of self-poisoning with this oleander are common in South-East Asia, because it is often used as a medicinal herb, and digoxin-specific Fab fragments have already been reported as effective antidote against oleander poisoning there. Our case has taught us that it is important to have this drug in the hospital pharmacy both for digitalis and oleander poisoning.

Aims: The aim of this study was to evaluate clinical outcomes and identify predictors of mortality in preterm infants with respiratory distress syndrome (RDS) treated in a tertiary Pediatric Intensive Care Unit (PICU). Methods: This retrospective study included 86 preterm infants diagnosed with RDS and treated between January 2015 and December 2024. Clinical data were extracted from medical records and included demographic and anthropometric parameters, perinatal history, associated neonatal diagnoses, ventilation type and duration, surfactant administration, use of inotropes and antibiotics, cranial ultrasound findings, and PICU length of stay. Results: Mortality was 18.6%, with the highest rates observed in extremely preterm infants (<28 weeks) and those with extremely low birth weight (<1000 g). Several clinical variables were significantly associated with survival: gestational age, birth weight, birth length, and Apgar scores at 1 and 10 min (all p ≤ 0.005). In multivariable logistic regression, each additional week of gestation (OR 0.72, 95% CI 0.59–0.87), higher birth weight (OR 0.998, 95% CI 0.997–0.999), and higher Apgar scores (OR 0.69 at 1 min; OR 0.60 at 10 min) were significantly associated with survival. Ventilation was required in 97.7% of infants, and outcomes differed significantly by ventilation modality (p = 0.021), with the lowest mortality observed in those treated with combined invasive and non-invasive ventilation. Resuscitation (p < 0.001) and inotropic support (p < 0.001) were strongly associated with death. Length of PICU stay and duration of ventilation were significantly shorter in non-survivors (p < 0.05). Surfactant therapy was used in 79.1% of infants but was not significantly associated with survival. Conclusions: Gestational age, birth weight, and early postnatal condition were the strongest predictors of survival in preterm infants with RDS. Non-invasive and combined ventilation were associated with better outcomes, whereas the need for resuscitation and inotropes indicated markedly higher mortality. These results highlight the importance of early stabilization and optimized respiratory support in improving outcomes.