Are single nucleotide polymorphisms in the IL-2 gene biomarkers for Hashimoto's thyroiditis?

Background and aims: Hashimoto's thyroiditis (HT) is an autoimmune disorder that can lead to hypothyroidism. The pathophysiology of HT involves the production of antithyroid antibodies that attack the thyroid tissue, causing inflammation and progressive fibrosis. Recent studies demonstrated a strong correlation between Interleukin-2 (IL-2) levels and the development of autoimmune diseases, suggesting that this cytokine may play a crucial role in the pathogenesis of HT. Methods: In this study, we determined the presence of the point mutation +114T/G in the IL-2 gene in patients with HT compared with a control group, and also the serum level of anti-thyroid peroxidase (TPOAbs) and anti-thyroglobulin (TgAbs) antibodies in HT patients with vs. without the mutation. The sequences of the IL-2 gene obtained from subjects were determined by the Sanger sequencing method. Results: Our study did not reveal that the +114T/G polymorphism of the IL-2 gene is a susceptibility or protective factor for HT. No significant correlations were observed between the reference genotype, hetero- and homozygous +114T/G polymorphism and TPOAbs, respectively TgAbs serum levels in HT patients. Conclusions: Further studies of more cases are needed to identify more polymorphisms in the IL-2 gene and study their correlations with HT.

The C55A Single Nucleotide Polymorphism in CTLA-4 Gene, a New Possible Biomarker in Thyroid Autoimmune Pathology Such as Hashimoto's Thyroiditis.

Hashimoto's thyroiditis (HT) is a chronic autoimmune disorder characterized by the production of autoantibodies against the thyroid gland. Different studies have shown that several genes may be associated with HT, which explains why patients often have family members with thyroiditis or other autoimmune diseases. The aim of this case-control study was to evaluate the correlation between polymorphisms at the level of exon 1 from the CTLA-4 gene and the susceptibility to developing HT. In this study, we found that there is no statistically significant association between the polymorphism rs231775 (A22G in exon 1) of the CTLA-4 gene and a genetic predisposition to HT. In contrast, a strong association was discovered for the first time between C55A in exon 1 of the CTLA-4 gene and HT. Our findings suggest that there is a genetic relationship between the CTLA-4 (+55A/C) genotype and the seropositivity against thyroid autoantigens, such as anti-thyroid peroxidase (ATPO) and anti-thyroglobulin antibodies (ATG).

Practical Aspects of Upper Gastrointestinal Bleeding in Children.

Upper gastrointestinal bleeding (UGB) in children is a potentially life-threatening condition that represents a challenge for pediatricians and pediatric surgeons. It is defined as bleeding from any location within the upper esophagus to the ligament of Treitz. UGB can have many causes that vary with age. The impact on the child is often proportional to the amount of blood lost. This can range from mild bleeding that is unlikely to cause hemodynamic instability, to massive bleeding that requires admission to the intensive care unit. Proper and prompt management are very important factors in reducing morbidity and mortality. This article aims to summarize current research regarding the diagnosis and treatment of UGB. Most of the data used in the literature published on this subject is extrapolated from adulthood.

Endoscopic Grading as a Predictor to Develop Strictures in Corrosive Esophagitis in Children.

INTRODUCTION: The incidence of corrosive esophagitis, also known as caustic esophagitis in children, is still increasing in developing countries, according to different clinical reports. Acids and alkalis are, in the same manner, involved in the pathogenesis of corrosive esophagitis in children. The aim of our study was to determine the incidence and endoscopic grading of corrosive esophagitis in a cohort of children from a developing country. MATERIALS AND METHODS: We performed a retrospective analysis of all pediatric patients who were admitted for corrosive ingestion at Pediatric Clinic II, Emergency Hospital for Children, Cluj-Napoca, over 10 years. RESULTS: A total of 22 patients consisting of 13 (59.09%) girls and 9 boys (40.91%) were found in the present research. The majority of children lived in rural areas (69.2%). The results of laboratory tests were not well correlated with the degree of the injury. White blood cell counts over 20,000 cells/mm3, an increase in the C-reactive protein level and hypoalbuminemia were noticed only in three patients with strictures. The lesions were associated with increased levels of the pro-inflammatory cytokines, including interleukin (IL)-2, IL-5 and Interferon-gamma. Severe late complications such as strictures have been noticed in children with grade 3A injuries. The endoscopic dilation was done after the six months endoscopy. None of the patients treated with endoscopic dilation required surgical intervention for esophageal or pyloric perforation or dilation failure. The majority of complications (such as malnutrition) were noticed in children with grade 3A injuries. In consequence, prolonged hospitalization has been required. The second endoscopy (done six months after ingestion) revealed stricture as the most common late complication (n = 13, 60.60%: eight patients with grade 2B and five with grade 3A). CONCLUSION: There is a low incidence of corrosive esophagitis in children in our geographic area. Endoscopic grading is a predictor of late complications such as strictures. Grade 2B and 3A corrosive esophagitis are likely to develop strictures. It is crucial to avoid strictures and to prevent malnutrition.

Proof of Concept for the Detection with Custom Printed Electrodes of Enterobactin as a Marker of Escherichia coli.

The rapid and decentralized detection of bacteria from biomedical, environmental, and food samples has the capacity to improve the conventional protocols and to change a predictable outcome. Identifying new markers and analysis methods represents an attractive strategy for the indirect but simpler and safer detection of pathogens that could replace existing methods. Enterobactin (Ent), a siderophore produced by Escherichia coli or other Gram-negative bacteria, was studied on different electrode materials to reveal its electrochemical fingerprint-very useful information towards the detection of the bacteria based on this analyte. The molecule was successfully identified in culture media samples and a future goal is the development of a rapid antibiogram. The presence of Ent was also assessed in wastewater and treated water samples collected from the municipal sewage treatment plant, groundwater, and tap water. Moreover, a custom configuration printed on a medical glove was employed to detect the target in the presence of another bacterial marker, namely pyocyanin (PyoC), that being a metabolite specific of another pathogen bacterium, namely Pseudomonas aeruginosa. Such new mobile and wearable platforms offer considerable promise for rapid low-cost on-site screening of bacterial contamination.

Extrahepatic Portal Vein Thrombosis, an Important Cause of Portal Hypertension in Children.

One of the most important causes of portal hypertension among children is extrahepatic portal vein thrombosis (EHPVT). The most common risk factors for EHPVT are neonatal umbilical vein catheterization, transfusions, bacterial infections, dehydration, and thrombophilia. Our study aimed to describe the clinical manifestations, treatment, evolution, and risk factors of children with EHPVT. METHODS: We analyzed retrospectively all children admitted and followed in our hospital with EHPVT between January 2011-December 2020. The diagnosis was made by ultrasound or contrast magnetic resonance imaging. We evaluated the onset symptoms, complications, therapeutic methods, and risk factors. RESULTS: A total of 63 children, mean age 5.14 ± 4.90 (33 boys, 52.38%), were evaluated for EHPVT during the study period. The first symptoms were upper gastrointestinal bleeding (31 children, 49.21%) and splenomegaly (22 children, 34.92%). Thrombocytopenia was present in 44 children (69.84%). The most frequent risk factors were umbilical vein catheterization (46 children, 73.02%) and bacterial infections during the neonatal period (30 children, 47.62%). Protein C, protein S, antithrombin III levels were decreased in 44 of the 48 patients tested. In 42 of these cases, mutations for thrombophilia were tested, and 37 were positive. Upper digestive endoscopy was performed in all cases, revealing esophageal varices in 56 children (88.89%). All children with gastrointestinal bleeding received an octreotide infusion. In 26 children (41.27%), variceal ligation was performed, and in 5 children (7.94%), sclerotherapy. Porto-systemic shunt was performed in 11 children (17.46%), and Meso-Rex shunt was done in 4 children (6.35%). The evolution was favorable in 62 cases (98.41%). Only one child died secondary to severe sepsis. CONCLUSIONS: EHPVT is frequently diagnosed in the last period in our region due to the increased use of umbilical vein catheterization. Furthermore, genetic predisposition, neonatal bacterial infections, and prematurity certainly play an important role in this condition. A proactive ultrasound assessment of children with risk factors for EHPVT should be encouraged for early diagnosis and treatment.

Infectious Esophagitis in Romanian Children: From Etiology and Risk Factors to Clinical Characteristics and Endoscopic Features.

OBJECTIVES: The aim of this study is to provide information about prevalence, etiology, risk factors, clinical characteristics and endoscopic features of various types of infectious esophagitis in children. METHODS: We performed a total of 520 upper gastrointestinal tract endoscopies in Pediatric Clinic II, Emergency Hospital for Children, Cluj-Napoca. Indications for endoscopy in our cohort were gastrointestinal tract symptoms such as dysphagia, heartburn, or appetite loss. RESULTS: The prevalence of infectious esophagitis in the study population was 2.11% (11 patients). Candida albicans (C. albicans) was the most frequent cause. Our data illustrates that herpes simplex virus (HSV)-induced esophagitis is common in immunocompromised patients and should be systematically suspected in cases of severe dysphagia, heartburn, or hematemesis. In the present study, all cytomegalovirus (CMV) esophagitis patients were immunocompromised. Immunodeficiency (81.8%) and prolonged antibiotic therapy with broad-spectrum antibiotics were by far the most important risk factors involved in the pathogenicity of the disease. Dysphagia, appetite loss, heartburn, epigastralgia, and hematemesis were the main clinical manifestations. Infectious esophagitis was associated with significant mortality. In four patients, endoscopy during life showed signs of infectious esophagitis; however, the precise etiology was only established post-mortem, in the pathological anatomy laboratory department. A risk factor involved in pathogenesis of post-mortem diagnosed infectious esophagitis is the DiGeorge syndrome for CMV and HSV patients. CONCLUSIONS: The study illustrates that infectious esophagitis should be considered in immunocompromised infants with prolonged antibiotic therapy with broad-spectrum antibiotics.

Pill -Induced Erosive Esophagitis in Children.

AIMS: Pill-induced esophagitis has been recognized in adults, but rarely in children. The aim of this article is to discuss endoscopic features, drugs implicated, prevention and treatment in pill-induced esophagitis in children. PATIENTS AND METHODS: Over a period of 4 years, 26 patients presented at our clinic with drug-induced esophageal ulcerations. All patients were diagnosed by means of endoscopy and treated with proton-pump inhibitors and prokinetics. The mean age of the children was 10.76 years. RESULTS: The ulcers were frequently located at the mid-esophagus. Odynophagea, retrosternal pain and dysphagia were the most common presenting symptoms. All children took pills (non-steroidal anti-inflammatory drugs, antibiotics - Doxycycline and ferrous sulfate) with little water and at bed time. The mean elapse between the drug intake and endoscopy was 4.96 days. The symptoms resolved within a maximum of one week of antireflux therapy. CONCLUSIONS: In pediatric cases treated by tablets or capsules, the possibility of medication-induced esophagitis should always be considered. The drug-induced esophagitis should be suspected in all patients presenting with chest pain and dysphagia. Physicians must warn the patients to take the pills and capsules with enough water and in the upright position.