Percutaneous Endoscopic Gastrostomy Tubes Can Be Considered Safe in Children: A Single-Center 11-Year Retrospective Analysis.

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.

Research methodology used in the 50 most cited articles in the field of pediatrics: types of studies that become citation classics.

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.

Characteristics of Children with Diabetic Ketoacidosis Treated in Pediatric Intensive Care Unit: Two-Center Cross-Sectional Study in Croatia.

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.

An overview of combined D-2- and L-2-hydroxyglutaric aciduria: functional analysis of CIC variants.

Combined D-2- and L-2-hydroxyglutaric aciduria (D/L-2-HGA) is a devastating neurometabolic disorder, usually lethal in the first years of life. Autosomal recessive mutations in the SLC25A1 gene, which encodes the mitochondrial citrate carrier (CIC), were previously detected in patients affected with combined D/L-2-HGA. We showed that transfection of deficient fibroblasts with wild-type SLC25A1 restored citrate efflux and decreased intracellular 2-hydroxyglutarate levels, confirming that deficient CIC is the cause of D/L-2-HGA. We developed and implemented a functional assay and applied it to all 17 missense variants detected in a total of 26 CIC-deficient patients, including eight novel cases, showing reduced activities of varying degrees. In addition, we analyzed the importance of residues affected by these missense variants using our existing scoring system. This allowed not only a clinical and biochemical overview of the D/L-2-HGA patients but also phenotype-genotype correlation studies.

Emotional and behavioral outcomes and quality of life in school-age children born as late preterm: retrospective cohort study.

Aim To determine the effect of late preterm birth and treatment at the intensive care unit (ICU) on school-age children's emotional and behavioral problems and quality of life (QoL). METHODS: Emotional and behavioral problems and QoL were investigated in 6-12-year-olds who were born late preterm at the University Hospital Center Split in the period from January 2002 to March 2008. The study included 126 late preterm children treated in ICU (LP-ICU group), 127 late preterm children not treated in ICU (LP-non-ICU group), and 131 full-term children treated in ICU (FT-ICU group). Emotional and behavioral difficulties were assessed using the Child Behavior Checklist. QoL was evaluated with the Royal Alexandra Hospital for Children Measure of Function questionnaire. The data was collected via telephone interview with mothers during 2014. RESULTS: Late preterm children had a nearly 5-fold risk for internalizing problems in comparison with FT-ICU children (OR 4.76, 95% confidence interval [CI] 2.37-9.56 and OR 4.82, 95% CI 2.25-10.37 in LP-ICU and LP-non-ICU children, respectively). They also had a greater risk for externalizing problems (OR 3.08, 95% CI 1.44-6.61 and OR 2.68, 95% CI 1.14-6.28, respectively) and total problems (OR 6.29, 95% CI 2.86-13.83 and OR 7.38, 95% CI 3.08-17.69, respectively) and a considerably increased risk for lower QoL (OR 12.79, 95% CI 5.56-29.41 and OR 5.05, 95% CI 2.04-12.48, respectively). CONCLUSION: Children born late preterm had a greater risk for emotional and behavioral problems and lower QoL during childhood than their full-term born peers and they experienced serious health problems upon birth.

Late preterm birth is a strong predictor of maternal stress later in life: Retrospective cohort study in school-aged children.

AIM: The aim of this study was to compare the level of stress in mothers of school-aged children born late preterm and admitted to the intensive care unit (ICU) with the level of maternal stress if a child was born late preterm and not admitted to the ICU as well as if a full-term child was admitted to the ICU. METHODS: In this retrospective cohort study the data were gathered via telephone interview with mothers. The Parenting Stress Index/Short Form was used to determine the level of stress in mothers. Background demographic characteristics, medically relevant variables, and the level of stress were tested using the chi-square test and Kruskal-Wallis test. Logistic regression was used in order to identify predictors of significant level of stress. RESULTS: Mothers of late preterm born children who were admitted to the ICU, as well as mothers of late preterm children who were not admitted had higher level of stress compared to mothers of full-term children. Namely, mothers of late preterm born children admitted to the ICU had 18-fold increase in risk for significant level of total stress (OR = 18.09; 95% CI 8.55 to 38.26) while 24-fold greater risk was observed in mothers of late preterm children who were not admitted to the ICU (OR = 24.05; 95% CI 10.66 to 54.26) in comparison to mothers of full-term born children. CONCLUSION: Results indicate that preterm birth and its complications are associated with a higher level of stress in mothers, that persists to school age.

Long-term quality of life of patients treated in paediatric intensive care unit.

UNLABELLED: The changes in long-term quality of life (QOL) of children treated in paediatric intensive care unit (PICU) were investigated in relation to their QOL before critical illness together with the influence of underlying chronic health condition and severity of illness estimated by Paediatric Index of Mortality 2 on the long-term outcome. This study included 189 children treated in PICU and 179 children from outpatient clinics as controls. QOL was evaluated according to the Royal Alexandra Hospital for Children Measure of Function (RAHC MOF). The long-term QOL in 70 % of children treated in PICU was good, although there was a significant diminution of QOL in children treated in PICU in comparison with their preadmission scores and with the children from outpatient clinics who served as controls (p < 0.001). Severity of illness had a significant impact on children's QOL (p = 0.016) 6 months after treatment in PICU. Twenty-four months after discharge, the RAHC MOF score was still decreased in 19 % of children treated in PICU, and in significantly more patients with a chronic health condition (CHC) treated in PICU, than in their peers from outpatient clinics (p = 0.029). Reduced QOL was significantly more frequent in children with neurodevelopmental disability than in children without CHC 24 months after discharge from PICU (p = 0.013). CONCLUSION: Acute illness has a significant impact both on children with and without CHC after treatment in PICU 6 months after discharge. Twenty-four months after discharge, comorbidity was identified as the decisive factor for diminished QOL in children after PICU treatment.

Clinical scoring systems in predicting health-related quality of life of children with injuries.

The aim of the study was to explore the association between Glasgow Coma Scale (GCS), Paediatric Index of Mortality (PIM2) and Injury Severity Score (ISS), and the long-term outcome of children with injuries. The health related quality of life (HRQL) was assessed by using the Royal Alexandra Hospital for children Measure of Function (RAHC MOF), 12 months post discharge. Out of 118 children with injuries (9% of all patients), 75 had injury of the head as the leading injury. There were no significant differences at admission in the severity of clinical condition, as expressed by PIM2 and ISS, between patients with head injuries and patients with other injured leading body regions. Children with head injuries had significantly worse HRQOL than children with other leading injured body region (p < 0.045), and children from road traffic accidents had significantly worse HRQL (p = 0.004), compared to other mechanisms of injury. HRQL correlated significantly with GCS (p = 0.027), but not with ISS and PIM2. As the conclusion, among all scoring systems applied, only GCS, which demonstrates severity of head injury, showed significant impact on long-term outcome of injured children.

The Impact of Vitamin D Levels on Clinical Manifestations of Multisystem Inflammatory Syndrome in Children: A Cross-Sectional Study.

BACKGROUND: Hyperinflammatory response that resembles Kawasaki disease may develop in children after COVID-19 disease, and it is called multisystem inflammatory syndrome in children. The cause of MIS-C is dysregulated innate immune response and a subsequent cytokine storm that results in endothelial damage. It has been determined that low levels of serum 25(OH)D increase the risk of developing immune-related diseases and disorders. METHODS: To determine the incidence of hypovitaminosis D, and a possible correlation between 25(OH)D levels and the clinical severity of MIS-C, 21 patients hospitalized in the University Hospital of Split due to MIS-C were evaluated. RESULTS: Hypovitaminosis D was detected in 95% of MIS-C patients. We found a significant relationship between the severity of MIS-C and 25(OH)D levels, as patients with more severe MIS-C had lower 25(OH)D. MIS-C patients with lower vitamin D levels had worse systolic and diastolic function of the left ventricle according to echocardiograms. There was no relationship between 25(OH)D levels and the tested laboratory inflammatory and cardiac markers. CONCLUSION: Hypovitaminosis D is very common in children with MIS-C and influences the severity of the disease. VD could be a new potential biomarker in MIS-C, and VD replacement therapy should be considered early on in the treatment of MIS-C.

A suicide attempt by ingestion of oleander leaves and treatment with digoxin-specific Fab antibody fragments.

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.

Functional outcome of children treated in intensive care unit.

OBJECTIVE: Outcome of patients is determined not only by severity of illness index, but also by the impact of patients' preadmission comorbid status. Therefore, we aimed at evaluating the outcome of patients treated in a pediatric intensive care unit, with special focus on the group of children with chronic diseases. METHODS: Data were obtained prospectively and outcome was assessed according to the Pediatric Overall Performance Category scale for 449 patients in a pediatric intensive care unit of the Split University Hospital. Functional performance was assessed as the preadmission score and the discharge score in patients with neurodevelopmental disabilities, patients with other chronic diseases, and those without chronic disease. RESULTS: The discharge functional status was significantly dependent on the preadmission functional status and on predicted mortality. Children with neurodevelopmental disabilities had the significantly worse baseline score and the significantly smaller deterioration of functional morbidity at discharge compared to children with no chronic disease and children with other chronic diseases. CONCLUSIONS: The Pediatric Overall Performance Category scale has proved its applicability in a small intensive care unit, with a heterogeneous population of patients. It should therefore be considered for regular evaluation of health care quality, as a simple and accurate tool. As opposed to other patients, functional status of children with neurodevelopmental disabilities was markedly influenced by their comorbidity. Their preadmission status was worse than the status of other children, and hence could not significantly deteriorate at discharge.

Thrombocytopenic purpura following envenomation by the nose-horned viper (Vipera ammodytes ammodytes): Two case reports.

RATIONALE: Two clinical cases are reported of envenomation by the nose-horned viper (Vipera ammodytes ammodytes) venom of a 9-year-old boy and of an 84-year-old woman. PATIENT CONCERNS: Both patients had been bitten on their extremities by such a snake in August near Split, a town in southern Croatia. DIAGNOSES: Clinical manifestation of envenomation was severe in the case of the boy, being characterized by a severe coagulopathy. This was only just apparent in the case of the elderly woman, who suffered extensive local edema and hematoma at the site of the bite, together with a neurotoxic effect-bilateral ptosis. This was the first occasion of thrombocytopenic purpura being observed in patients envenomed by nose-horned viper venom. This unexpected clinical finding was characterized by an unusually profound thrombocytopenia of 5 and 10 × 10/L platelets of the respective patients on their admission to the hospital, together with purpura, observed on the face and thorax of both individuals. In the most serious cases, such pathology can be life threatening if not promptly recognized and treated. INTERVENTIONS: The patients recovered quickly on receiving the specific antivenom along with all the usual supportive treatments. OUTCOMES: No serious sequels were noticed at the moment of discharge. LESSONS: Our finding constitutes an important message to clinicians to consider the possibility of such complications in the case of nose-horned viper envenomation.

Effects of immune modulation therapy in the first Croatian infant diagnosed with Pompe disease: a 3-year follow-up study.

Pompe disease is a storage disorder characterized by deficient or absent activity of the enzyme acid alpha-glucosidase. As a result of ineffective metabolism, glycogen accumulates in muscle tissues. Patients with a classic infantile-onset form present by the first few months of life with hypertrophic cardiomyopathy and muscle weakness. If left untreated, these patients rapidly die of cardiorespiratory failure. A cross-reactive immunological material (CRIM)-negative status is predictive of high anti-alglucosidase alpha antibody titers. However, CRIM-positive patients also sometimes develop robust antibody titers. High antibody titers complicate therapeutic management, and those patients have a worse clinical outcome of enzyme replacement therapy (ERT).Four years ago, we successfully used an immune modulation therapy (IMT) protocol in a CRIM-positive infantile-onset patient with Pompe disease in whom ERT had to be discontinued because of severe infusion-associated reactions. She was found to be positive for anti-alglucosidase alpha antibodies. IMT (rituximab, methotrexate, and intravenous gammaglobulin) was started, and ERT was safely reintroduced during the IMT induction phase without any complications. Antibodies disappeared; IMT was tapered and discontinued; and cardiomyopathy steadily improved. During more than 3 years of follow-up, she remained ventilator dependent, and no gains in motor skills were noticed. The antibodies are still undetectable, and no adverse reactions associated with IMT had occurred. The cardiomyopathy is gradually increasing, but there is still ~ 50 % reduction as compared with the highest value measured. Although the reversal of clinical decline in our CRIM-positive and antibody-positive infant cannot be solely attributed to IMT, this protocol proved itself efficient and safe.

Immune Modulation Therapy in a CRIM-Positive and IgG Antibody-Positive Infant with Pompe Disease Treated with Alglucosidase Alfa: A Case Report.

Pompe disease is characterized by deficiency or absence of activity of the lysosomal enzyme acid alpha-glucosidase. As a result of ineffective metabolism, glycogen progressively accumulates in muscle tissues. Patients with an aggressive classic infantile-onset form generally rapidly die of cardiorespiratory failure. A cross-reactive immunological material (CRIM)-negative status is predictive of high anti-alglucosidase alfa antibody titers and usually a poor clinical outcome of enzyme replacement therapy (ERT). CRIM-positive patients can also develop robust antibody titers complicating therapeutic management.We successfully used an immune modulation therapy (IMT) protocol in a CRIM-positive infantile-onset patient with Pompe disease in whom infusions had to be temporarily discontinued because of safety concerns despite administration of pre-infusion medication. Prior to discontinuation, she had shown signs of clinical deterioration and continuous ventilation support through a tracheostomy was required. She was found to be positive for anti-alglucosidase alfa antibodies (1:6,400). IMT (rituximab, methotrexate and intravenous gamma globulin) was started, ERT was safely reintroduced during the IMT induction phase and, subsequently, the enzyme dose was increased, all without any complications. Antibodies disappeared, IMT was tapered and discontinued, and cadiomyopathy steadily improved. During 1 year of follow-up, she remained ventilator dependent and no gains in motor skills were noticed; motor functions will be closely monitored during sustained ERT.Although the reversal of clinical decline in our CRIM-positive and antibody-positive infant with Pompe disease cannot be solely attributed to IMT, our experiences with this protocol may be helpful to other physicians encountering comparable therapeutic dilemmas.

Late ventriculoperitoneal shunt infection caused by Shewanella algae.

We present a case of ventriculitis and peritonitis in a child with ventriculoperitoneal shunt, which occurred 5 years after the surgery. The infection developed after contact with seawater and began as otitis. For the first time, Shewanella algae, a marine microorganism, was identified as the cause of ventriculoperitoneal shunt infection.

Life-threatening valproate overdose successfully treated with haemodialysis.

Valproate (VPA) poisoning is an increasing clinical problem. The most common finding in VPA overdose is the depression of the central nervous system, which may progress to coma and death. This type of poisoning is difficult to treat, as no antidote exists. This report describes a case with a 16-year-old girl who poisoned herself with valproate. Initial treatment included naloxone, but she did not respond. She became comatose, with serum VPA concentration of 1320 microg mL(-1). Three sessions of haemodialysis were performed, effectively eliminating VPA and decreasing the serum concentration. The patient regained consciousness and fully recovered.To our knowledge, this is the highest serum VPA concentration reported by now in children aged 16 or less. Haemodialysis has proved to be the treatment of choice for life-threatening acute VPA overdose in children.

Neurodevelopmental disabilities and quality of life after intensive care treatment.

AIM: To analyze the quality of life after Pediatric Intensive Care Unit (PICU) treatment and compare the differences between quality of life in children who suffer chronic health conditions, and those who do not, post discharge from PICU. METHOD: Quality of life was assessed using the Royal Alexandra Hospital for Children (RAHC) Measure of Function which incorporates measures of domains that delineate severity or impact of disease symptoms, physical disability, mobility, emotional distress, behavior, deviation from normal growth and development, impairment in social rules, and performance at school and in leisure activities. RESULTS: Families of 371 children were contacted for RAHC Measure of Function scoring. The results showed that the majority of children with no chronic condition (88.8%), as well as those with a chronic condition other than neurodevelopmental disability (81.6%) had minimal ongoing health problems and good quality of life. Only 21.4% of children with neurodevelopmental disabilities fell into this category, 39.3% had poor quality of life and 39.3% had fair quality of life. CONCLUSION: The results suggest that the majority of patients discharged from the PICU go on to have a good quality of life. The quality of life of patients with other chronic condition did not differ significantly from children who did not suffer from a chronic condition, with the majority of both groups having minimal residual health problems. Conversely, children with neurodevelopmental disabilities were found to have a higher level of health problems and only a fair quality of life compared with the other two groups.

The influence of chronic health conditions on susceptibility to severe acute illness of children treated in PICU.

OBJECTIVES: Our study aimed to assess differences in the susceptibility to severe acute illness in children with and without chronic health conditions treated in a pediatric intensive care unit (PICU). PATIENTS AND METHODS: Data on age, gender, need for ventilator support, length of stay, as well as other parameters for the Paediatric Index of Mortality (PIM2) score were collected. Data were analyzed and compared across three patient groups: those with a neurodevelopmental disability, those with a chronic condition other than a neurodevelopmental disability, and those with no chronic condition. Reasons for admission of patients were classified according to the Australia and New Zealand Paediatric Intensive Care Registry (ANZPIC Registry) diagnostic codes. In the multidisciplinary, seven-bed, level I PICU of the Split University Hospital, the admission data were collected prospectively for 591 consecutively admitted patients aged