ANOTHER FACE OF EPSTEIN-BARR VIRUS INFECTION: ACUTE ACALCULOUS CHOLECYSTITIS WITH CHOLESTASIS IN A PREVIOUSLY HEALTHY FIVE-YEAR-OLD GIRL WITH PRIMARY INFECTION.

Acute acalculous cholecystitis (AAC) is a rare disease, particularly in children. The clinical and laboratory presentation of AAC is variable. The diagnosis is based on radiological criteria. AAC is an atypical and rare complication of Epstein-Barr virus (EBV) infection, therefore we present a girl with AAC and cholestasis due to EBV primary infection. Conservative treatment and careful monitoring was followed by clinical, radiological and laboratory improvement, and finally complete recovery. Our aim was to highlight the importance of recognizing AAC as a differential diagnosis in children with abdominal pain and/or acute cholestasis.

TRANSIENT PSEUDOHYPOALDOSTERONISM SECONDARY TO URINARY TRACT INFECTION IN A MALE INFANT WITH UNILATERAL HYDRONEPHROSIS DUE TO PRIMARY OBSTRUCTIVE MEGAURETER: A CASE REPORT.

We present a case of transient form of type 1 pseudohypoaldosteronism (S-PHA) in a 1.5-month-old male infant who presented with lethargy, failure to thrive, severe hyponatremia (Na=118 mmol/L), hypochloremia (Cl=93 mmol/L) and fever due to urinary tract infection. Potassium levels were normal. Markedly elevated serum aldosterone level and elevated serum renin confirmed the diagnosis of pseudohypoaldosteronism. Renal ultrasound showed grade III hydronephrosis on the left kidney while contrast-enhanced voiding urosonography excluded the existence of vesicoureteral reflux, which raised suspicion of obstructive uropathy at the level of vesicoureteral junction. Serum sodium normalized after several days of intravenous fluids and antibiotic therapy, after which oral supplementation of sodium was introduced. The levels of 17-hydroxyprogesterone, adrenocorticotropic hormone, cortisol and thyroid-stimulating hormone were normal. Functional magnetic resonance urography conducted at the age of 3 months confirmed the diagnosis of primary congenital obstructive megaureter and the infant was referred to a pediatric surgeon. Although a rare occurrence, S-PHA can be a potentially life-threatening condition in infants if not recognized and treated appropriately. Therefore, serum concentrations of electrolytes should be obtained in every child diagnosed with obstructive anomaly of the urinary tract and/or acute cystopyelonephritis. On the other hand, every child diagnosed with S-PHA should be evaluated for obstructive anomaly of the urinary tract.

"The role of L. reuteri DSM17938 in nutritional recovery and treatment of constipation in children and adolescents with anorexia nervosa - a randomized, double blind, placebo controlled study".

BACKGROUND: Anorexia nervosa (AN) carries the risk of potentially irreversible medical complications, especially in children and adolescents. Constipation is frequent and difficult to manage. Due to the symptoms it causes, constipation can further compromise nutritional rehabilitation. OBJECTIVE: To investigate the role of probiotics (Lactobacillus reuteri DSM 17938) in children and adolescent with AN. DESIGN, SETTING AND PARTICIPANTS: Randomized, double blind, placebo controlled study in 31 female pediatric AN patients with constipation, referred to nutritional therapy in Pediatric Gastroenterology Department, Sestre milosrdnice University Hospital Centre in Zagreb. METHODS: At hospitalization, patients were randomly assigned into two groups; one taking L. reuteri, and other placebo for 3 months, along with the conventional nutritional rehabilitation. Patients were followed 3 months after stopping the treatment. The primary outcome was relief of constipation, assessed after 3 months, while secondary outcomes were normalization of body weight, stool frequency and consistency, relief of dyspepsia, weight gain and recovery of malnutrition regarding bone density and vitamin D3 levels. RESULTS: The study showed statistically significant difference between the two groups considering the stool frequency (6.4 vs. 4.2 stools/week; p < 0.05) and normalization of body weight (93 vs. 63%; p = 0.04) after 6 months, but no significant effect on the rate of relief of constipation (87 vs. 64%; p = 0.22) at 3 months. In the L. reuteri group, the normalization of BMD was achieved in 8/15, whereas in the placebo group, in 3/16 patients. However, there was no statistically significant difference compared to the placebo group regarding the BMD recovery as well as the normalization of D3 levels (p = 0.056). CONCLUSIONS: Probiotics may serve as simple and safe adjuvant therapy of constipation in childhood AN and contribute to faster nutritional recovery. Although a statistically significant difference between the two group in relief of constipation could not be shown after 3 months, a benefit from probiotics could be in increasing stool frequency and nutritional recovery in childhood AN after six months. Registered under ClinicalTrials.gov Identifier no. NCT02004288.

Significance of Extra-Esophageal Symptoms in Pediatric Gastroesophageal Reflux Disease.

Introduction Current practice guidelines in gastroesophageal reflux disease (GERD) often require invasive diagnostic testing. Objective The aim of the present study was to evaluate the significance of extra-esophageal symptoms and reliability of a screening risk score that is simple to use. Methods A longitudinal retrospective single-institution cohort study. Setting: A university clinical hospital tertiary referral center. The present study enrolled pediatric patients with symptoms suggestive of GERD: epigastric pain, occasional nausea, regurgitation, tasting acid in the oral cavity, chronic cough, hoarseness of voice, frequent throat clearing. The patients underwent 24-hour esophageal pH monitoring and fiber-optic laryngoscopy. The correlations between the local findings, anamnestic and objective measurement data were analyzed. Results The present study evaluated 89 pediatric patients. Patients with asthma presented significantly more often with adjoining gastrointestinal symptoms ( p = 0.0472). Patients that were obese were linked to a higher rate of reports of gastrointestinal symptoms ( p = 0.0495). After the patients had been assigned to newly developed risk groups, obesity showed to be significantly more frequent in patients placed in higher risk groups ( p < 0.0001) for a positive GERD diagnosis. Conclusion Patients with leading symptoms of asthma presented significantly more often with adjoining gastrointestinal symptoms. Obesity showed to be significantly more frequent in patients placed in higher risk groups for a positive GERD diagnosis.

Incidence and Geographical Variability of Pediatric Inflammatory Bowel Disease in Croatia: Data From the Croatian National Registry for Children With Inflammatory Bowel Disease.

The aim of this study was to determine the annual incidence and geographic distribution of pediatric inflammatory bowel disease (IBD) in Croatia. This is a prospective, cohort, multicenter observational study based on the data obtained from the Croatian national registry for children with IBD. Children and adolescents younger than 18 years diagnosed with IBD, in time period between June 1, 2016, and May 31, 2017, were recruited. In total, 51 new cases were identified; 19 Crohn's disease, 28 ulcerative colitis, and 8 IBD-unclassified. Male preponderance of all 3 types of the disease was noticed. The median age at diagnosis was 14.8 years. The calculated annual incidence of pediatric IBD per 100 000 persons per year was 7.05 (2.63 for Crohn's disease, 3.87 for ulcerative colitis, and 0.55 for IBD-unclassified). A north to south gradient was observed with almost 2 times higher incidence in the northern region of the country.

IBD phenotype at diagnosis, and early disease-course in pediatric patients in Croatia: data from the Croatian national registry.

BACKGROUND: Pediatric inflammatory bowel disease (IBD) presents with extensive phenotype. The aim of this study was to determine the phenotype of pediatric IBD patients in Croatia at diagnosis and follow-up. METHODS: Children were prospectively recruited into Croatian IBD national registry. Data on diagnostic evaluation, therapy and 1-year follow-up were collected. RESULTS: A total of 51 newly diagnosed patients were recruited (19 Crohn's disease (CD), 28 ulcerative colitis (UC) and 4 IBD-unclassified (IBD-U)). Most common location in CD was ileocolonic disease (52.6%), and pancolitis in UC (53.6%). The recommended complete diagnostic algorithm was performed only in 29.4% of patients. First-line therapy used in CD was exclusive enteral nutrition for remission induction (84.2%) and azathioprine for maintenance (73.7%). In patients with UC, aminosalicylates were the most common drug used (89.3%). By the end of the first year 41.2% of CD and 53.9% of UC patients had one or more relapses and required treatment escalation. CONCLUSION: Our data confirm extensive intestinal involvement in pediatric IBD and relatively high relapse rate during the first year of follow-up. More effort should be invested on the national level to implement more stringent adherence to the current European guidelines. IMPACT: The key message of our article is that pediatric IBD in Croatia shows extensive intestinal involvement with high relapse rates in first year of follow-up. It is the first cohort study reporting on the phenotype of pediatric IBD in Croatia, but also investigates adherence to diagnostic and therapeutic European guidelines which is not commonly reported. The study is national based, thus having the greatest impact on Croatian health care,stressing out that more effort should be invested on the national level to implement more stringent adherence to the current European guidelines.

PREDICTORS OF EATING DISORDER RISK IN ANOREXIA NERVOSA ADOLESCENTS.

- The purpose of the present study was to examine the association among the risk of eating disorder (ED), psychological adjustment, empathy, attachment style and thin-ideal internalization among adolescents with anorexia nervosa (AN), as compared to a healthy control (HC) group. The Questionnaire of General Data, the Eating Disorders Inventory-3 (EDI-3), the Questionnaire of Sociocultural Attitudes Towards Appearance-3 (SATAQ-3), the Experiences in Close Relationships-Revised (ECR-R) and the Basic Empathy Scale (BES) were administered to 35 female adolescents with AN and 35 HC adolescents. Eating disorder risk was found to be highest in AN females with higher levels of general psychological maladjustment (GPMC), followed by HC females with higher thin-ideal internalization. In the AN group, attachment style and thin-ideal internalization in combination with GPMC were not indicated as significant predictors of eating disorder risk. Study data provide support to conceptualizations of EDs that emphasize the role of general psychological maladjustment in the development of EDs.

Co-occurrence of celiac disease and ulcerative colitis in a 12-year-old girl.

Celiac disease (CD) and inflammatory bowel diseases (IBD) are separately well-described entities, but the co-occurrence in children has been very rarely reported until today. According to the literature, this case about 12-year-old girl would be the fifth case ever published about co-occurrence in children. We presume that there should be a higher comorbidity prevalence than that described. Distinguishing both diseases in one patient could be difficult due to the overlapping symptoms, but it is very important considering completely different therapeutic approaches.

Unusually difficult clinical presentation of an infant suffering from congenital Cytomegalovirus (CMV) infection combined with alpha 1-antitrypsin (A1AT) deficiency.

Congenital Cytomegalovirus (CMV) infection and alpha 1-antitrypsin (A1AT) deficiency are separately well described entities, but their simultaneous occurrence can pose a special challenge to a clinician, especially dealing with optimal diagnostic as well as therapeutic approach. Congenital CMV infection is the most common vertically transmitted infection in developed countries. In 85-95% of newborns it runs asymptomatic, while in others it is presented with jaundice, petechias, hepatosplenomegaly and central nervous system damage. A1AT deficiency is on the other hand, the most common genetic liver disease in children, and the clinical spectrum varies from the accidentally detected increased levels of transaminases through to the severe infant cholestasis that can progress to cirrhosis. The following case report describes a two-month old male with severe clinical presentation of congenital CMV infection probably exacerbated due to A1AT deficiency comorbidity. The clinical manifestations and unusually difficult clinical signs this infant presented lead to assumption that the additional liver damage exists. Extensive laboratory analyses were performed, including PCR for CMV DNA, A1AT serum concentration, A1AT genotyping, followed and confirmed with phenotyping. Patient was treated parenteral with ganciclovir, what continued with oral valganciclovir and supportive therapy. Intensive and thorough supportive treatment of the infant resulted in satisfactory progress and excellent outcome. Patient was followed-up till the age of 18 months. The presented case provides excellent example about successful overcoming obstacles in differential diagnosis of A1AT in neonates and infants. Medical charts analysis was the methodology used in making this report.

Clinical features and diagnostic reliability in paediatric laryngopharyngeal reflux.

OBJECTIVE: The aim of this study was to assess the validity of current diagnostic approaches in pediatric laryngopharyngeal reflux (PLPR). Clinical status findings and 24h double probe oesophageal pH monitoring results in children with suspected PLPR and/or GERD were analyzed and a clinically useful probability score was developed. METHODS: This is a retrospective longitudinal cohort study including 89 pediatric patients who underwent preliminary oropharyngoscopy, and then nasal fibre optic laryngoscopy and ambulatory 24h oesophageal pH monitoring in a tertiary pediatric and otorhinolaryngology hospital center. The patients' parents gave written informed consent for diagnostic testing. Statistical analysis was performed using standard descriptive statistics. Associations between variables were assessed using Fisher's exact test, Mann-Whitney test and Kruskal-Wallis test for non-parametric paired samples. RESULTS: Patients' age spanned 1-18 years with a median of 11.2. Out of the 89 patients, 56 were girls, and 33 were boys. All of the patients underwent nasal fibre optic laryngoscopy and 24h double probe pH monitoring. Out of 89 examined children, 50 had PLPR. Out of the 50 positive for PLPR, 46 had a positive clinical finding, with a sensitivity of 92% (95% CI: 80.75-97.73%) and specificity of 10.26% (95% CI: 2.93-24.24%). Boys have GERD significantly more often than girls (p<0.0001), and have a worse result of pH monitoring (p<0.0001). The most common finding was an injected and granulated oropharynx accompanied by posterior laryngitis (54/89). Patients with leading symptoms of asthma had significantly worse GERD scores (p=0.0493). The patients were then reassigned to newly developed risk categories and a significant correlation with a positive PLPR diagnosis was found (p=0.0262). CONCLUSIONS: The significance of a thorough otorhinolaryngologic and paediatric examination and patient history taking is still paramount, with additional benefit in diagnosing the disease arising from 24h oesophageal pH monitoring in select patients. This study brings to light new relationships between clinical symptoms and objective findings and presents a novel attempt to classify the likelihood of diagnosis. Patient stratification could help clinicians in defining groups at high risk and support a timely, cost-effective and precise diagnostic evaluation and proper therapy.

Correlation of UGT1A1 TATA-box polymorphism and jaundice in breastfed newborns-early presentation of Gilbert's syndrome.

OBJECTIVE: The etiology of jaundice in otherwise healthy breastfed newborns that can present as early-onset exaggerated physiologic jaundice, or late breast milk jaundice (BMJ), is not yet entirely understood. This study tested the hypothesis that molecular marker for Gilbert's syndrome (GS), UGT1A1 TATA-box polymorphism, is associated with this disorders. METHODS: We have investigated the UGT1A1 polymorphism frequency and its relation to severity of hyperbilirubinemia and jaundice duration among 220 exclusively breastfed term newborns; 57 of them with non-physiologic hyperbilirubinemia (NH), and 163 with BMJ, and in 187 healthy controls. RESULTS: Significant differences in TA7/7 genotype frequency were established. The highest frequency was observed among the newborns with BMJ (42.0%), intermediate in the NH group (24.6%), while the controls had the lowest TA7/7 frequency (12.8%). Linear increase in TA7/7 frequency was observed depending on the duration of jaundice, peaking at 42.4% in newborns with the longest jaundice duration. Positive correlation between the serum bilirubin levels and the TATA-box length was established in all groups. CONCLUSION: This study provides evidence that UGT1A1 TATA-box polymorphism is an important risk factor for developing jaundice in term breastfed newborns, presented as either early non-physiologic hyperbilirubinemia or breast milk jaundice. These results further support the original Odell's idea of neonatal jaundice as an early presentation of GS.