Congenital Hyperinsulinism Caused by Mutations in ABCC8 Gene Associated with Early-Onset Neonatal Hypoglycemia: Genetic Heterogeneity Correlated with Phenotypic Variability.

Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (KATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset HH caused by ABCC8 gene mutations. In the first patient, who presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330-1)del] that correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C>T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of the focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine) positron emission tomography/computed tomography (PET/CT) was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH.

Impact of COVID-19 on Pediatric Inflammatory Bowel Diseases-From Expectations to Reality.

Viral infections have always been considered a threat to global health, with numerous outbreaks across time. Despite the relative recent experience with coronavirus-associated diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), severe acute respiratory syndrome-2's (SARS-CoV-2) continuous evolution displays a different behavior. With a tropism for both respiratory and digestive mucosa, coronavirus disease 2019 (COVID-19) and inflammatory bowel disease (IBD) seem to share a particular common background. Current literature offers evidence that viral alteration of the immune system, inflammatory intestinal tissue damage, increased intestinal permeability, incomplete viral clearance with viral antigen persistence, and intestinal dysbiosis, might explain SARS-CoV-2-IBD relationship in terms of etiopathogenesis and evolution. The hyperinflammatory state that both entities have in common explains the lack of success of current IBD therapy, raising the need for new personalized therapeutic options, with better outcomes for IBD and COVID-19 as well. This review aims to summarize the current available data on pediatric IBD evolution, management, and outcomes in the post-COVID period, with an emphasis on the particular aspects of the SARS-CoV-2-IBD relationship in children.

Exploring the Microbial Landscape: Gut Dysbiosis and Therapeutic Strategies in Pancreatitis-A Narrative Review.

The gut microbiota is emerging as an important contributor to the homeostasis of the human body through its involvement in nutrition and metabolism, protection against pathogens, and the development and modulation of the immune system. It has therefore become an important research topic in recent decades. Although the association between intestinal dysbiosis and numerous digestive pathologies has been thoroughly researched, its involvement in pancreatic diseases constitutes a novelty in the specialized literature. In recent years, growing evidence has pointed to the critical involvement of the pancreas in regulating the intestinal microbiota, as well as the impact of the intestinal microbiota on pancreatic physiology, which implies the existence of a bidirectional connection known as the "gut-pancreas axis". It is theorized that any change at either of these levels triggers a response in the other component, hence leading to the evolution of pancreatitis. However, there are not enough data to determine whether gut dysbiosis is an underlying cause or a result of pancreatitis; therefore, more research is needed in this area. The purpose of this narrative review is to highlight the role of gut dysbiosis in the pathogenesis of acute and chronic pancreatitis, its evolution, and the prospect of employing the microbiota as a therapeutic intervention for pancreatitis.

Pattern of Primary Resistance of Helicobacter pylori to Clarithromycin among Pediatric Patients from North-Eastern Romania.

BACKGROUND: Helicobacter pylori antibiotic resistance has increased worldwide and affects the effectiveness of current therapies. The recommended first-line empiric treatment should be tailored to the local clarithromycin resistance rate. This study aimed to determine the pediatric patient profile and rate of clarithromycin resistance for patients diagnosed with Helicobacter pylori by gastric biopsy. METHODS: We studied 84 positive gastric samples for Helicobacter pylori. Positive results were confirmed by a rapid urease test and histopathological examination, with the type of gastritis established according to the Sydney System. Gastric biopsy samples were stored in RNA saver. Clarithromycin resistance was determined by a real-time polymerase chain reaction-based molecular assay after RNA-DNA extraction. RESULTS: Of the 84 biopsy samples analyzed, 35 (41.6%) were resistant to clarithromycin. Clarithromycin resistance was found mainly in girls (80%) with a mean age of 15 years (range 6-17 years). The history of prior exposure to clarithromycin was 91.6%. The concordance between the histopathological examination and the PCR test was 100%. CONCLUSIONS: One in 2.4 children infected with Helicobacter pylori had a strain resistant to clarithromycin. This resistant strain may be a reason for treatment failure in Romanian children, yet this is uninvestigated. The high rate of bacterial resistance to this antibiotic among children indicates the need for susceptibility testing before therapy.

The Effectiveness of Different Eradication Schemes for Pediatric Helicobacter pylori Infection-A Single-Center Comparative Study from Romania.

INTRODUCTION: In Romania, studies on the pediatric population regarding H. pylori infection or bacterial resistance to antibiotics are limited. Eradication treatment of this infection still raises important problems in medical practice. This study aims to compare the effectiveness of three eradication therapies used against H. pylori infection in the pediatric population. METHODS: The prospective study enrolled children aged 6-17 years who were first diagnosed with H. pylori infection. Patients received a randomized treatment either the therapy with clarithromycin (CLR), the therapy with metronidazole (MTZ) or sequential therapy. The effectiveness of the eradication treatment was evaluated after 4-8 weeks from the end of the therapy by testing fecal antigen. RESULTS: 149 patients were enrolled over 18 months. The eradication rates were 49.5% for the treatment scheme with proton pump inhibitor (PPI) + amoxicillin (AMO) + MTZ, 26.7% for PPI + AMO + CLR and 23.8% for sequential therapy. MTZ therapy was superior to CLR therapy, but sequential therapy was not. Side effects were recorded for PPI + AMO + CLR with 39.6%, followed by sequential therapy 37.7%, and only 22.6% for PPI + AMO + MTZ. CONCLUSIONS: Therapy with MTZ can achieve a higher eradication rate as a first-line treatment in the case of H. pylori infection. Taking into account that Romania is in an area with increased resistance to CLR, MTZ therapy could be a promising alternative.

Self-Medication Patterns during a Pandemic: A Qualitative Study on Romanian Mothers' Beliefs toward Self-Treatment of Their Children.

Self-medication represents a significant healthcare and health policy issue worldwide, both in developed and underdeveloped countries. Currently, the COVID-19 pandemic is considered a relevant context that could subtly trigger self-medication behavior because of limited access to health care services and the threat of infection with the SARS-CoV-2 virus. While the previous research conducted with quantitative methodologies reported a dramatically increased rate of self-medication around the world, qualitative inquiries on the subjective experience with self-medicine remain scarce in medical and related fields of study. For this purpose, a qualitative study with semi-structured interviews was undertaken to better understand how Romanian mothers (n = 18) applied self-treatment with their children by avoiding medical advice during the COVID-19 pandemic. The results showed that the COVID-19 pandemic did not affect the prevalence of self-medicine among the pediatric population as parents achieved a degree of awareness of self-treatment of their children due to the general context of the outbreak of the COVID-19 pandemic.

Helicobacter pylori Infection in a Pediatric Population from Romania: Risk Factors, Clinical and Endoscopic Features and Treatment Compliance.

Background and Objectives: The aim of this study was to investigate the association between H. pylori positivity with specific symptoms, risk factors and endoscopic patterns among the pediatric population in northeastern Romania. Materials and Methods: A prospective study was performed in 18 months on 185 children aged 6−18 years with an indication for upper digestive endoscopy. Demographic, anamnestic, symptomatic, endoscopic and histologic data were recorded. Results: Of 116 H. pylori-positive children, the most affected group was 15−17 years. Most (65.5%) of them were girls, with a significant association (p < 0.001). The majority (66.4%) lived in a rural area and 47.4% of children had an unsafe source of water and lived in overcrowded houses with no basic sanitary comfort. The most frequent symptom was epigastric pain (56.9%), and the main endoscopic appearance was nodularity and hyperemia. Patients diagnosed with H. pylori started triple-therapy treatment for 14 days. Only 13.8% stopped the treatment, mainly because of a misunderstanding of the treatment protocol (9.5%). Conclusions: Romanian teen girls living in rural areas are at high risk for H. pylori infection. Epigastric pain and endoscopic nodularity of the gastric mucosa were associated with the infection. As the resistance of the bacteria is unknown in our country, future research is needed in order to improve the eradication rate.

Magnesium Orotate and the Microbiome-Gut-Brain Axis Modulation: New Approaches in Psychological Comorbidities of Gastrointestinal Functional Disorders.

Magnesium orotate has been cited in the medical literature for the past three years as a possible adjuvant in some pediatric and adult gastroenterological disorders associated with dysbiosis. Studies also focus on the possibility of adding magnesium orotate in psychiatric disorders' treatment, such as major depression and anxiety. The most relevant element in these studies is the efficiency of magnesium orotate therapy in cases with both gastroenterological and psychiatric symptoms. This article proposes a literature review, focused on the studies published in the last three years, targeting magnesium orotate treatment and probiotic supplementation in patients with both digestive and psychiatric symptoms. Moreover, this review will compare the efficiency of magnesium orotate and probiotics within both the pediatric and adult communities, focusing on the possibility of gut-brain axis modulation and its involvement in the clinical evolution of these patients.

Assessing the Opinion of Mothers about School-Based Sexual Education in Romania, the Country with the Highest Rate of Teenage Pregnancy in Europe.

Background and Objectives: Without mandatory school-based education, Romania is a leading European country in teen pregnancy. This survey aimed at assessing the level of knowledge and the opinions about sexual education and sexual-related issues among mothers of female teenagers aged 13-18 years old. Material and Methods: The survey was conducted between 2015 and 2017 and had four parts, collecting data about sociodemographic variables, the level of knowledge about sexuality, sexually transmitted diseases, and contraception. The respondents were mothers of female teenagers hospitalized in a tertiary pediatric clinic. Data were analyzed using IBM Statistical Package for Social Sciences (SPSS) Statistics for Windows, version 25 (Inc., Chicago, IL, USA). Results: One hundred and thirty-five mothers (42.46 ± 6.81 years old) were included in the research. Most of them were from rural areas, had graduated secondary school, were Christian-orthodox, married, and with a stable job. More than half of the mothers (61.42%) declared that they personally knew adolescents that were already mothers. In great proportion, mothers proved good knowledge about sexual education, contraception, and STDs. They considered that the minimum age for becoming married, in general, is about M = 18.62 ± 2.09 years old but in the case of their daughters, mothers appreciated that the best age would be 23.56 ± 9.37. Mothers considered that they had good communication with their daughters (M = 4.28 ± 0.99) and two-thirds sustained that they had discussed with them about sexual activity, pregnancy, sexually transmitted diseases, and contraception. In case of unwanted pregnancy of their daughters, one-third of the mothers (38.50%) would advise their girls to continue the pregnancy and 7.40% mentioned the termination of pregnancy. Two-thirds of them (74.10%) agreed to school-based sexual education. In the order of preferred sources for sexual education, mothers mentioned parents (85.90%), teachers (33.30%), and family doctors (24.40%). Comparative results regarding their own sex life and that of their daughters are presented. Conclusions: School-based programs should meet parental beliefs about sexuality and sexual education. School, as a creator of values and models, should find the golden ratio to better shape the personal, familial, and social needs for the healthy sexual behavior of the new generation.

Some Risk Factors of Chronic Functional Constipation Identified in a Pediatric Population Sample from Romania.

We conducted an observational study over a 1-year period, including 234 children aged 4-18 years and their caregivers and a matching control group. 60.73% of the children from the study group were males. Average age for the onset of constipation was 26.39 months. The frequency of defecation was 1/4.59 days (1/1.13 days in the control group). 38.49% of the patients in the sample group had a positive family history of functional constipation. The majority of children with functional constipation come from single-parent families, are raised by relatives, or come from orphanages. Constipated subjects had their last meal of the day at later hours and consumed fast foods more frequently than the children in the control sample. We found a statistically significant difference between groups regarding obesity/overweight and constipation (χ2 = 104.94, df = 2, p < 0.001) and regarding physical activity and constipation (χ2 = 18.419; df = 3; p < 0.001). There was a positive correlation between the number of hours spent watching television/using the computer and the occurrence of the disease (F = 92.162, p < 0.001, and 95% Cl). Children from broken families, with positive family history, defective dietary habits, obesity and sedentary behavior, are at higher risk to develop chronic functional constipation.

Chronic Functional Constipation and Encopresis in Children in Relationship with the Psychosocial Environment.

Functional constipation is an issue for both the patient and his/her family, affecting the patient's psychoemotional balance, social relations, and their harmonious integration in the school environment. We aimed to highlight the connection between chronic constipation and encopresis and the patient's psychosocial and family-related situation. Material and Method. 57 patients with ages spanning from 6 to 15 were assessed within the pediatric gastroenterology ward. Sociodemographic, medical, and psychological data was recorded. The collected data was processed using the SPSS 20 software. Results. The study group consisted of 57 children diagnosed with encopresis (43 boys (75.44%) and 14 girls (24.56%)), M = 10.82 years. It was determined that most of the children came from urban families with a poor socioeducational status. We identified a level of studies of 11.23 ± 5.56 years in mothers, while fathers had an average number of 9.35 ± 4.53 years of study. We also found a complex relationship between encopretic episodes and school performances (F = 7.968, p = 0.001, 95% Cl). Children with encopresis were found to have more anxiety/depression symptoms, greater social problems, more disruptive behavior, and poorer school performance. Conclusions. The study highlights the importance of the family environment and socioeconomic factors in manifestations of chronic constipation and encopresis.

Upper gastrointestinal bleeding in children from a hospital center of Northeast Romania.

BACKGROUND: The aim of this study was to investigate the common etiologies, clinical and biological patterns of upper gastrointestinal bleeding (UGIB) in children from a hospital center in Northeast Romania. METHODS: This seven-year retrospective study was performed from 2007 to 2013 in St. Mary Children's Emergency Hospital, Jassy, Romania and included all children who referred to our center with UGIB exteriorized by hematemesis or melena. Endoscopy was performed under conscious sedation/general anesthesia after the informed consent was obtained. RESULTS: One hundred and three patients aged 1-18 years were included in this study. There were 57 males and 46 females with male to female ratio 1.2:1; 43.69% presented with hematemesis, 31.07% had melena and 25.24% had both. The most common causes of UGIB were erosive gastritis (33.98%), followed by esophagitis (14.56%), duodenitis (11.65%), duodenal ulcer (10.68%), gastric ulcer (5.83%), esophageal varices (4.85%), Mallory-Weiss syndrome (1.94%); multiple etiologies counted for 16.50% cases. A certain bleeding source was found in 34.95% cases, a possible one in 39.81% of the patients; the source could not be ascertained in 25.24% of cases. Nonsteroidal anti-inflammatory drug (NSAID) consumption was documented in in 17.51% of patients. The incidence of H. pylori infection was 36.89%. CONCLUSIONS: The most common cause of of upper GI bleeding in our series was gastritis, followed by oesophagitis and duodenitis. Most of the patients presented with hematemesis; previous consumption of NSAIDs and H. pylori infection were associated with gastroduodenal ulceration and bleeding. Early endoscopy was associated with a higher detection rate of the bleeding source.

Foreign Bodies Ingestion in Children: Experience of 61 Cases in a Pediatric Gastroenterology Unit from Romania.

The ingestion of foreign bodies is a worldwide pediatric pathology. We assessed the clinical, endoscopic, and therapeutic aspects of this condition in a pediatric gastroenterology unit. We reviewed 61 patients (median age of 3.25 ± 4.7 years). The most frequently ingested objects were coins (26.23%), unidentified metal objects (13.11%), bones (8.19%), batteries, and buttons (6.55%). The clinical features we encountered included abdominal pain (55.73%), vomiting (34.42%), and asymptomatic children (29.5%). Routine X-ray examination enabled finding the foreign body in 42 of the cases. An esophagogastroduodenoscopy was performed within 24-72 hours. 25 cases resulted in a negative endoscopy (40.98%), 19 objects (31.14%) were removed using a polypectomy snare, and extraction failure occurred in 17 patients (27.86%). 28 foreign bodies were passed without incidents; in 14 cases, the swallowed objects were never found. In one case, a battery was stuck in the esophageal folds and led to tracheal-esophageal fistula and bronchopneumonia and later to esophageal stenosis. We report a large proportion of foreign bodies that could not be identified or removed due to lack of early endoscopy and poor technical settings. Batteries and sharp objects lead to severe complications and preschool-age children are at high risk for such events.

Unusual Endoscopic Findings in Children: Esophageal and Gastric Polyps: Three Cases Report.

Isolated polyps of the upper digestive tract are rarely diagnosed in children, being usually an incidental finding during endoscopic exploration.The diagnostic, therapy, and outcome of these lesions are based on endoscopy and pathology.In a 5-year period, clinical features, topography, size, pathology, therapeutics, and progression of esophagogastric polyps founded in children addressed to our pediatric gastroenterology unit were studied.The authors encountered 3 lesions in teenagers aged 13 to 17 years two males (2M), from a total number of 2140 upper digestive endoscopies (0.14%). All patients presented with pirosis, epigastric pain, and vomits; one of the children had end-stage renal disease and Kabuki syndrome. Endoscopic and pathologic findings were 2 esophageal polyps, an inflammatory one, and another containing goblet cells and a double-headed hyperplastic gastric polyp. Two patients received proton pump inhibitors without any improvement in subsequent endoscopic evaluations.The difficulties related to age group, underlying conditions, debatable response to acid suppression, and limited experience in pediatric therapeutic endoscopy selected significantly the effectiveness of treatment.The rarity of these lesions requires an individualized management, the endoscopic diagnostic, and therapeutic gesture depending on the symptoms, type, location, comorbidities, and team experience.