Congenital sodium diarrhea (CSD) refers to an intractable diarrhea of intrauterine onset with high fecal sodium loss. CSD is clinically and genetically heterogeneous. Syndromic CSD is caused by SPINT2 mutations. While we recently described four cases of the non-syndromic form of CSD that were caused by dominant activating mutations in intestinal receptor guanylate cyclase C (GC-C), the genetic cause for the majority of CSD is still unknown. Therefore, we aimed to determine the genetic cause for non-GC-C non-syndromic CSD in 18 patients from 16 unrelated families applying whole-exome sequencing and/or chromosomal microarray analyses and/or direct Sanger sequencing. SLC9A3 missense, splicing and truncation mutations, including an instance of uniparental disomy, and whole-gene deletion were identified in nine patients from eight families with CSD. Two of these nine patients developed inflammatory bowel disease (IBD) at 4 and 16 years of age. SLC9A3 encodes Na(+)/H(+) antiporter 3 (NHE3), which is the major intestinal brush-border Na(+)/H(+) exchanger. All mutations were in the NHE3 N-terminal transport domain, and all missense mutations were in the putative membrane-spanning domains. Identified SLC9A3 missense mutations were functionally characterized in plasma membrane NHE null fibroblasts. SLC9A3 missense mutations compromised NHE3 activity by reducing basal surface expression and/or loss of basal transport function of NHE3 molecules, whereas acute regulation was normal. This study identifies recessive mutations in NHE3, a downstream target of GC-C, as a cause of CSD and implies primary basal NHE3 malfunction as a predisposition for IBD in a subset of patients.

ObjectivesThe aim of this study was to compare the different diagnostic approaches in detection of gastroesophageal reflux disease in children presented with symptoms suggesting gastroesophageal reflux disease.MethodsThe study design was cross sectional. The study retrospectively included all children who underwent combined multiple intraluminal impedance and pH (pH-MII) monitoring due to gastrointestinal and/or extraesophageal symptoms suggesting gastroesophageal reflux disease at University Children's Hospital in Belgrade, from July 2012 to July 2016.ResultsA total of 218 (117 boys/101 girls), mean age 6.7 years (range 0.06–18.0 years), met the inclusion criteria. Gastroesophageal reflux disease was found in 128 of 218 children (57.4%) by pH-MII and in 76 (34.1%) children by pH metry alone. Using pH-MII monitoring as gold standard, sensitivity of pH-metry was lowest in infants (22.9%), with tendency to increase in older age groups (reaching 76.4% in children ≥ 9 years). The sensitivity of pH-metry alone in children with extraesophageal symptoms was 38.1%, while the sensitivity of pH-metry in children with gastrointestinal symptoms was 63.8%. Reflux esophagitis was identified in 31 (26.1%) of 119 children who underwent endoscopy. Logistic regression analysis showed that best predictors of endoscopic reflux esophagitis are the longest acid episode (OR = 1.52, p<0.05) and DeMeester reflux composite score (OR = 3.31, p<0.05). The significant cutoff values included DeMeester reflux composite score ≥ 29 (AUC 0.786, CI 0.695–0.877, p<0.01) and duration of longest acid reflux ≥ 18 minutes (AUC 0.784, CI 0.692–0.875, p<0.01).ConclusionsThe results of our study suggested that compared with pH-metry alone, pH-MII had significantly higher detection rate of gastroesophageal reflux disease, especially in infants. Our findings also showed that pH-MII parameters correlated significantly with the endoscopically confirmed erosive esophagitis.

Objectives: The aim of this study was to assess the epidemiological, clinical, endoscopic, and pathohistological characteristics of pediatric eosinophilic esophagitis (EoE) in Serbia. Method: All children aged 0–18 years diagnosed with EoE in the period between 2010 and 2017 at the University Children’s Hospital in Belgrade, Serbia, were retrospectively enrolled. Results: EoE was diagnosed in 35 children (12.45 ± 3.77 years) with a male predominance (74%). The median incidence rate was estimated to be 0.85 per 100,000 children per year with the highest rate estimated at 3.17 per 100,000 children in 2017. Dysphagia (71.4%) and food impaction (40%) were dominant symptoms. Inflammatory endoscopic changes were found in 74.3% and fibrostenotic changes in 62.9% of the children. The esophageal biopsy rate was low (6.8%), especially in children with reflux and nonspecific symptoms. Subepithelial fibrosis was found in only 20% of the patients. Since 2016, the number of biopsy samples has increased, but the sampling rate of lamina propria is still low (<50%). The correlation between the number of biopsies and lamina propria acquisition was strong (rs = 0.773, p < 0.05). In 2 immunocompetent adolescents, EoE was diagnosed after successful treatment of infectious esophagitis. Conclusions: An increase in the incidence of EoE in Serbian children is evident. The biopsy rate in children with nonspecific and reflux symptoms should be increased, as well as the number of biopsy samples for the detection of subepithelial fibrosis. In immunocompetent children with infectious esophagitis, EoE should be suspected and endoscopy may be recommended after successful treatment of infection.

The aim of our study was to research and evaluate cardiovascular and respiratory stability, clinical efficacy, and safety of two different anesthetic agents in pediatric patients who underwent Pulse dye (wavelength 595 nm, pulse duration 0-40 ms, power 0-40 J) and CO (wavelength 10,600 nm, intensity-fraxel mod with SX index 4 to 8, power 0-30 W) laser procedure. This prospective non-blinded study included 203 pediatric patients ASA I-II, aged between 1 month and 12 years who underwent short-term procedural sedation and analgesia for the laser procedure. After oral premedication with midazolam, 103 children were analgo-sedated with ketamine and fentanyl (K group) and 100 with ketofol and fentanyl (KT group). Vital signs, applied drug doses, pulse oximetry, and parental satisfaction questionnaire were used to compare these two groups. Statistical differences were tested using Student's t test, Mann-Whitney U test, chi-square test, and Fisher's exact test. Receiver operating characteristic (ROC) curve analysis was used to assess the cut-off value of the duration of anesthesia predicting apnea. Tachycardia was recorded in a significantly higher number of patients who received ketamine as the anesthetic agent (35.9 vs. 3% respectively). Hypertension was also significantly more frequent in patients who received ketamine in comparison with patients who received ketofol (25.2 vs. 3%). Laryngospasm was not observed in both examined groups. There was no statistically significant difference between groups in satisfaction of parents and doctors. Apnea and respiratory depression occurred significantly more frequent in ketofol than in ketamine group (12 vs. 0.97% and 13 vs. 0%). Based on ROC analysis for apnea, we found a significantly higher number of patients with apnea in the ketofol group when duration of anesthesia was longer than 17 min. Our study has shown that ketofol is more comfortable than ketamine in short-term laser procedures in children, causing less hemodynamic alteration with mild respiratory depression and less post-procedural adverse events.

PurposePreterm newborns, due to many factors, are at increased risk for poor neural development, intraventricular hemorrhages, infections, and higher rate of mortality. The aim of this study was to evaluate the risk factors associated with poor outcome in preterm neonates with late-onset neonatal sepsis (LONS) who had posthemorrhagic hydrocephalus and underwent neurosurgical procedures for treatment of the hydrocephalus.Patients and methodsPreterm neonates who had undergone insertion of ventriculoperitoneal shunt or Ommaya reservoir, during the 10-year period at University Children’s Hospital, were retrospectively analyzed. According to the presence or absence of LONS, patients were divided into LONS group and non-LONS group. In both groups, we analyzed demographic and clinical data as well as nondependent factors. Additionally, we evaluated the patients who had lethal outcome in respect to all the analyzed factors.ResultsA total of 74 patients were included in the study, 35 in LONS group and 39 in control group. Patients in LONS group were born significantly earlier with lower birth weight, needed significantly higher O2 inspiratory concentration, and had longer duration of mechanical ventilation when compared to the nonseptic group. Five patients in LONS group had lethal outcome, and for these patients we identified a grade American Society of Anaesthesiologists score of 4 (P=0.000), ductus arteriosus persistens (P=0.000), bronchopulmonary dysplasia (P=0.003), and pneumothorax (P=0.003) as independent preoperative risk factors for lethal outcome.ConclusionNeurosurgical procedures are relatively safe in neonates with posthemorrhagic hydrocephalus without LONS after birth. However, if LONS is present, various conditions such as preoperative high grade American Society of Anaesthesiologists score, ductus arteriosus persistens, bronchopulmonary dysplasia, and pneumothorax markedly increase the risk for a lethal outcome after the operation.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening dermatological conditions that are characterized by mucosal erosions, epidermal detachments and erosions. The most common causes of SJS and TEN are drugs; other causes such as systemic lupus erythematosus (SLE), vaccinations and infections have been rarely implicated. We present the case of a 14-year-old female patient with acute pancreatitis as an initial manifestation of systemic lupus erythematosus, complicated by the toxic epidermal necrolysis with a fatal outcome. She initially presented with abdominal pain, fever, vomiting, and intolerance to oral intake and elevated pancreatic enzyme levels. Systemic lupus erythematosus was diagnosed secondary when her condition has been already complicated by the toxic epidermal necrolysis. The administration of corticosteroids and high doses of intravenous immunoglobulin did not lead to positive effects in the treatment of our patient.

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Symptom-based diagnosis of gastroesophageal reflux disease (GERD) is not specific due to high prevalence of disorders that can mimic GERD. Conventional pH monitoring, combined pH-MII (multiple intraluminal impedance) monitoring and esophagogastroduodenoscopy are diagnostic methods most frequently used in children.Combined pH-MII monitoring is the most accurate diagnostic method for detecting GERD in children, which tends to become the gold standard. In infants and probably in children with extraesophageal symptoms, MII gives the greatest contribution to the validity of pH-MII monitoring. High prevalence of functional heartburn, in children older than 8 years, suggests the importance of pH-MII monitoring in this age group as well. The majority of studies showed age differences in the chemical composition of refluxate. Weakly acid reflux is more common in infants and is often associated with symptoms, whereas acid reflux is more common in older children and adolescent. Sensitivity of endoscopy is very low compared to pH-MII monitoring as a reference test. Although endoscopy is the method of choice for the confirmation of reflux esophagitis, pH-MII parameters are promising indicators of mucosal integrity, but further studies are needed.The major problem with pH-MII monitoring is a lack of normative data for children. Therefore, the standardization is mandatory. For the present pH-MII monitoring has limited impact on treatment due to the absence of effective therapy for weakly acid reflux, suggesting that further studies should be directed in this direction.