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Aim: The purpose of this study was to evaluate irisin, myonectin and high-sensitivity interleukin-6 (hs IL-6) levels in obese children and adolescents and to determine the association of these parameters with metabolic dysfunction-associated steatotic liver disease (MASLD) in children., Methods: Sixty-one overweight/obese children with suspected liver disease and seventeen healthy controls were included in the study. MASLD was diagnosed according to the latest consensus. Circulating irisin, myonectin and hs IL-6 were measured by enzyme-linked immunosorbent assay (ELISA)., Results: The study group included 38 children meeting MASLD criteria and 23 children without diagnosed hepatic steatosis. The concentrations of the analysed myokines were comparable in the MASLD and non-MASLD groups. Patients with MASLD were further divided according to the severity of hepatic steatosis. Significantly higher levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltransferase, uric acid and irisin were observed in patients with severe hepatic steatosis compared to mild hepatic steatosis. There were borderline statistically significant positive correlations of irisin with ALT and AST., Conclusion: We revealed that elevated irisin levels were associated with the degree of hepatic steatosis in MASLD. We also found a borderline significant positive association of irisin with liver enzymes., (© 2024 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aim of the Study: Metabolic-associated fatty liver disease (MAFLD) requires close monitoring due to its increased incidence and progression to fibrosis, cirrhosis and even hepatocellular carcinoma. The search for non-invasive markers to diagnose liver fibrosis is ongoing. The aim of our study was to evaluate the serum levels of growth differentiation factor-15 (GDF-15), thrombospondin-2 (TSP2), pentraxin 3 (PTX3) and angiopoietin-like protein 8 (ANGPTL8) in children with MAFLD., Material and Methods: Fifty-six overweight/obese children with suspected liver disease were included in this prospective study. MAFLD was diagnosed according to the latest consensus. Vibration-controlled transient elastography (TE) was performed to detect clinically significant liver fibrosis. Serum concentrations of GDF-15, TSP2, PTX3 and ANGPTL8 were measured by enzyme-linked immunosorbent assay (ELISA)., Results: Liver steatosis was diagnosed in abdominal ultrasound in 31 (55.36%) overweight/obese patients who were classified as the MAFLD group. Aspartate aminotransferase (AST)/platelet ratio (APRI) and liver stiffness measurement (LSM) values and TSP2 concentrations showed significantly higher values in patients in MAFLD than in the non-MAFLD group. TSP2 was significantly positively correlated with alanine transaminase (ALT), AST, γ-glutamyltransferase (GGT) and APRI in the study group. The receiver operating characteristics (ROC) analysis showed that the area under the curve (AUC) of LSM, APRI and serum TSP2 was significant for predicting MAFLD in obese children. In the multivariable regression model, LSM was the only significant parameter associated with the diagnosis of MAFLD in children., Conclusions: TSP2 may be a potential biomarker of hepatocyte injury in pediatric patients with MAFLD. None of the examined biomarkers were found to be effective non-invasive markers of liver fibrosis in children., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 Clinical and Experimental Hepatology.)

BACKGROUND Respiratory tract infections (RTIs) in children often involve a complex interplay between viruses and bacteria. This study aimed to evaluate clinical presentation in children under 5 years old diagnosed with non-COVID-19 bacterial and viral respiratory tract co-infections between October 2021 and May 2022 in Białystok, Poland. MATERIAL AND METHODS We recruited 100 children under 5 years with RTIs who tested negative for SARS-CoV-2. Nasopharyngeal swabs were screened for 19 viruses and 7 bacterial strains using molecular assays. RESULTS Viral pathogens were detected in 71% of patients and bacterial pathogens were detected in 59%. The most common pathogens were Haemophilus influenzae (n=48), rhinoviruses (n=32), and Streptococcus pneumoniae (n=30). Single pathogens were detected in 36%, dual in 37%, triple in 15%, and quadruple in 2%. Bacterial pathogens were co-detected with viruses in 40 cases, mostly with rhinoviruses (n=15). Two different viruses were found in 14 children and the most common co-detection was adenovirus with rhinovirus (n=5); dyspnea (63% vs 11%) and wheezing (75% vs 22%) were more common in children with human bocavirus. Fever was a common symptom in children with human adenovirus (88% vs 58%). Detection of bacteria and multiple detections were more common in day-care attendees, but were not associated with clinical picture of RTI. CONCLUSIONS Consistent with previous studies, we found a high prevalence of rhinoviruses, despite ongoing implementation of non-pharmaceutical interventions to contain the COVID-19 pandemic. Co-detection of 2 different respiratory pathogens was frequent, but we found no evidence that this was associated with the severity of infections.

BACKGROUND In recent years, an increasing prevalence of Helicobacter pylori resistance to antibiotics has been observed. The aim of this study was to assess antibiotic resistance of Helicobacter pylori in previously untreated children from northeast Poland. MATERIAL AND METHODS Inclusion criteria comprised suspicion of Helicobacter pylori infection based on the presence of Helicobacter pylori antigen in the stool and/or characteristic macroscopic lesions seen on esophagogastroduodenoscopy. Samples of the gastric and/or duodenal mucosa were collected from 82 children with a median age of 13 years (range 3-17) during esophagogastroduodenoscopy between February 2019 and May 2022. The material was cultured, and positive Helicobacter pylori strains were tested for drug resistance to amoxicillin, metronidazole, and clarithromycin using the quantitative antibiotic concentration gradient stripe method E-test. RESULTS Based on biopsy culture, Helicobacter pylori infection was confirmed in 50 (61%) children. Helicobacter pylori resistance was most common to clarithromycin (n=19; 38%), followed by metronidazole (n=15; 30%), and the least frequent to amoxicillin (n=13; 26%). The resistance to 1 antibiotic was found in 14 children (28%). Double-drug resistance was noted in 3 children (6%) and triple drug resistance in 9 children (18%). In the whole group, 24 children (48%) were susceptible to all 3 antibiotics. CONCLUSIONS In this study, conducted for the first time in treatment-naïve children in northeast Poland, we found a high proportion of Helicobacter pylori strains resistant to at least 1 antibiotic. Our results may help in the appropriate choice of antibiotics for treatment of Helicobacter pylori in our region.

The coexistence of inflammatory bowel disease (IBD) with pancreatic pathology is rare in children. A retrospective analysis of data from 1538 children diagnosed with IBD in 2014-2021 was conducted to determine the frequency and causes of pancreatitis and asymptomatic hyperlipasemia (HL) or hyperamylasemia (HA) in this group of patients. Among the 176 children (11.4%) with pancreatic involvement (PI), acute pancreatitis (AP) was diagnosed in 77 children (43.8%), and HA or HL was observed in 88 children (50.0%). Only a few patients were diagnosed with autoimmune or chronic pancreatitis (6.2%). PI was observed at the time of the IBD diagnosis in 26.1% of the cases. A total of 54.5% of the patients had moderate to severe IBD, and 96% had colonic involvement at the time of diagnosis of PI. Idiopathic PI was the most common (57%), followed by drug-induced PI (37%) and azathioprine (AZA). In patients with AZA-induced AP, the successful introduction of 6-mercaptopurine (6-MP) to therapy was noted in 62.5% of the children. Our results suggest that routine monitoring of pancreatic enzymes in patients with IBD should be performed, especially after the initiation of the AZA treatment. The presence of transient HA/HL in IBD does not necessarily indicate pancreatic pathology.

The incidence of gallstone disease has increased in recent years. The pathogenesis of cholelithiasis is not fully understood. The occurrence of the disease is influenced by both genetic and environmental factors. This article reviews the literature on cholelithiasis in children, with the exception of articles on hematological causes of cholelithiasis and cholelithiasis surgery. The aim of this review is to present the latest research on the pathogenesis of gallstone disease in children. The paper discusses the influence of all factors known so far, such as genetic predisposition, age, infections, medications used, parenteral nutrition, and comorbidities, on the development of gallstone disease. The course of cholelithiasis in the pediatric population is complex, ranging from asymptomatic to life-threatening. Understanding the course of the disease and predisposing factors can result in a faster diagnosis of the disease and administration of appropriate treatment.

Human factors research can play an important role in the successful design of infrastructure to support future mobility. Through engaging users and stakeholders early in the design process we can gain insights before the physical environments are built. This paper presents data from a truly novel application of Virtual Reality (VR), where user experience and wayfinding were evaluated within an emerging future transport infrastructure to support urban air mobility (UAM) - the urban airport (aka vertiports). Urban airports are located in city centres where drones or 'flying cars' would land and take off from. Previous quantitative studies have investigated passenger experience in traditional airports using field observation and surveys, but this paper is the first to present qualitative research on user experience in this emerging mobility infrastructure using an immersive VR environment. Twenty participants completed a series of six scenarios aimed at understanding customer 'exciters' and 'pain points' within an urban airport. Results and recommendations from this empirical research will help inform the design of all future mobility infrastructure solutions, through improving user experience before the infrastructure is physically deployed. Finally, this paper highlights the benefits of engaging users at an early stage of the design process to ensure that future transport infrastructure will be accessible, easy to navigate and a pleasure to use., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

(1) Background: Disturbances in the sphingolipid profile are observed in many diseases. There are currently no data available on the evaluation of sphingolipids and ceramides in cholelithiasis in children. The aim of this study was to evaluate the concentrations of sphingolipids in the sera of pediatric patients with gallstones. We determined their relationship with anthropometric and biochemical parameters. (2) Methods: The concentrations of sphingolipids in serum samples were evaluated using a quantitative method, ultra-high-performance liquid chromatography-tandem mass spectrometry. (3) Results: The prospective study included 48 children and adolescents diagnosed with gallstones and 38 controls. Serum concentrations of total cholesterol (TC); sphinganine (SPA); ceramides-C14:0-Cer, C16:0-Cer, C18:1-Cer, C18:0-Cer, C20:0-Cer and C24:1-Cer; and lactosylceramides-C16:0-LacCer, C18:0-LacCer, C18:1-LacCer, C24:0-LacCer and C24:1-LacCer differed significantly between patients with cholelithiasis and without cholelithiasis. After adjusting for age, gender, obesity and TC and TG levels, we found the best differentiating sphingolipids for cholelithiasis in the form of decreased SPA, C14:0-Cer, C16:0-Cer, C24:1-LacCer and C24:0-LacCer concentration and increased C20:0-Cer, C24:1-Cer, C16:0-LacCer and C18:1-LacCer. The highest area under the curve (AUC), specificity and sensitivity were determined for C16:0-Cer with cholelithiasis diagnosis. (4) Conclusions: Our results suggest that serum sphingolipids may be potential biomarkers in pediatric patients with cholelithiasis.

Background: Alcohol consumption by adolescents is responsible for a number of adverse health and social outcomes. Despite the well-established effect of alcohol use on the development of alcoholic liver disease, the relationship between the pattern of alcohol consumption and liver fibrosis is still unclear. This study is a follow-up to work on liver damage from alcohol intoxication. The aim of our study was to explore the early effects of alcohol intoxication on liver fibrosis in adolescents. Methods: The prospective study included 57 adolescents aged 14−17 years admitted to the emergency department (ED) from February 2017 to June 2018 due to acute alcohol intoxication. Serum levels of amino terminal propeptide of type III procollagen (PIIINP), type IV collagen, matrix metallopeptidase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) were determined by enzyme-linked immunosorbent assays. Results: There were significant differences in MMP-9 (p = 0.02) and TIMP-1 (p = 0.007) levels between the study and control groups. Liver parameters and selected markers of fibrosis were similar in groups in terms of blood alcohol concentrations (BAC). MMP-9 was positively correlated with alanine aminotransferase (ALT) (r = 0.38; p = 0.004) and total bilirubin (r = 0.39; p = 0.004). Positive significant correlations were also found between TIMP-1 and ALT (r = 0.47; p < 0.001), AST (r = 0.29; p = 0.03) and total bilirubin (r = 0.32; p = 0.02). In receiver operating characteristic (ROC) analysis, MMP-9 (AUC = 0.67, p = 0.02) and TIMP-1 (AUC = 0.69, p = 0.003) allowed for the differentiation of patients with and without alcohol intoxication. Conclusion: Our results show that even a single episode of alcohol intoxication in adolescents can lead to imbalance in markers of fibrosis.

Adipose tissue is the main source of adipokines and therefore serves not only as a storage organ, but also has an endocrine effect. Chemerin, produced mainly in adipocytes and liver, is a natural ligand for chemokine-like receptor 1 (CMKLR1), G-protein-coupled receptor 1 (GPR1) and C-C motif chemokine receptor-like 2 (CCRL2), which have been identified in many tissues and organs. The role of this protein is an active area of research, and recent analyses suggest that chemerin contributes to angiogenesis, adipogenesis, glucose homeostasis and energy metabolism. Many studies confirm that this molecule is associated with obesity in both children and adults. We conducted a systematic review of data from published studies evaluating chemerin in children with various disease entities. We searched PubMed to identify eligible studies published prior to February 2022. A total of 36 studies were selected for analysis after a detailed investigation, which was intended to leave only the research studies. Moreover, chemerin seems to play an important role in the development of cardiovascular and digestive diseases. The purpose of this review was to describe the latest advances in knowledge of the role of chemerin in the pathogenesis of various diseases from studies in pediatric patients. The mechanisms underlying the function of chemerin in various diseases in children are still being investigated, and growing evidence suggests that this adipokine may be a potential prognostic biomarker for a wide range of diseases.

Background: Underage drinking is associated with health risk behaviors. Serum keratin-18 (CK18) levels are increased in liver diseases and may be biomarkers of outcome. The purpose of this study was to determine if the total CK18 (M65) or caspase-cleaved CK18 (M30) levels were different in adolescents admitted to hospital because of alcohol intoxication and controls with excluded liver diseases., Methods: A prospective study included 57 adolescents after alcohol use and 23 control subjects. The concentrations of M30 and M65 in the serum samples were evaluated using an enzyme-linked immunosorbent assay., Results: The median age was 15 (14-17) years and 49% were male. There were significant differences in M65 levels between the study and control groups ( p = 0.03). The concentrations of M30 and M65 were insignificant in adolescents divided into subgroups according to blood alcohol concentrations (BAC). Significant positive correlations were found between BAC and M65 levels ( p = 0.038; r = 0.3). In receiver operating characteristic (ROC) analysis M65 (cut-off = 125.966 IU/l, Se = 70.2%, Sp = 43.5%) allowed to differentiate between patients with and without alcohol intoxication (AUC = 0.66, p = 0.03)., Conclusion: M65 appears to be a promising non-invasive biomarker of hepatocyte injury during alcohol intoxication in adolescents. Moreover, a higher concentration of M65 may indicate early organ injury before the increase in the activity of liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

Background and Objectives: Inflammatory bowel disease (IBD) is a chronic condition and mainly affects the intestines, however, the involvement of the other organs of the gastrointestinal tract (upper part, pancreas, and liver) have been observed. The coexistence of IBD with pancreatic pathology is rare, however, it has been diagnosed more frequently during recent years in the pediatric population. This article reviews the current literature on the most common pancreatic diseases associated with IBD in the pediatric population and their relationship with IBD activity and treatment. Materials and Methods: We performed a systematic review of data from published studies on pancreatic disorders, also reported as extraintestinal manifestations (EIMs), among children with IBD. We searched PubMed and Web of Science to identify eligible studies published prior to 25 April 2020. Results: Forty-four papers were chosen for analysis after a detailed inspection, which aimed to keep only the research studies (case control studies and cohort studies) or case reports on children and only those which were written in English. The manifestations of IBD-associated pancreatic disorders range from asymptomatic increase in pancreatic enzymes activity to severe disease such as acute pancreatitis. Acute pancreatitis (AP) induced by drugs, mainly thiopurine, seems to be the most- often-reported pancreatic disease associated with IBD in children. AP associated with other than drug etiologies, and chronic pancreatitis (CP), are rarely observed in the course of pediatric IBD. The pancreatic involvement can be strictly related to the activity of IBD and can also precede the diagnosis of IBD in some pediatric patients. The course of AP is mild in most cases and may occasionally lead to the development of CP, mainly in cases with a genetic predisposition. Conclusions: The involvement of the pancreas in the course of IBD may be considered as an EIM or a separate co-morbid disease, but it can also be a side effect of IBD therapy, therefore a differential diagnosis should always be performed. As the number of IBD incidences with concomitant pancreatic diseases is constantly increasing in the pediatric population, it is important to include pancreatic enzymes level measurement in the workup of IBD.

Background and Aim: Adipokines and hepatokines are proteins secreted by adipose tissue and the liver. To date, the levels of adipokines and hepatokines in cholelithiasis have only been evaluated in studies in adult patients. The purpose of our research was to assess the levels of circulating adipokines: chemerin, vaspin, progranulin, retinol-binding protein 4 (RBP-4) and hepatokine: fibroblast growth factor 21 (FGF-21) and to compare their concentrations in paediatric patients with and without cholelithiasis., Methods: The prospective study included 54 children and adolescents diagnosed with gallstones and 26 controls. Fasting serum levels of adipokines and hepatokine were determined by enzyme-linked immunosorbent assays., Results: The serum levels of chemerin, FGF-21 and RBP-4 were significantly higher in children and adolescents with gallstones compared to the control group. Elevated levels of triglycerides, RBP-4, and a homeostatic model for assessing insulin resistance (HOMA-IR) were observed in overweight or obese patients compared to patients with normal weight and cholelithiasis. Chemerin concentrations were increased in the normal-weight children and adolescents with cholelithiasis compared to the control group. Children and adolescents with gallstones and abnormal weight had significantly higher levels of chemerin, FGF-21 and RBP-4 than healthy controls., Conclusion: Elevated serum chemerin levels were significantly higher in non-obese patients with cholelithiasis than in non-obese controls, suggesting a potential role of chemerin in the development of cholelithiasis in children and adolescents., (© 2020 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background: An increase in the incidence of eosinophilic esophagitis worldwide is being observed in children. The aim of the study was to analyze the incidence, clinical manifestations, biochemical markers and endoscopic features of children with eosinophilic esophagitis in comparison to patients with non-eosinophilic esophagitis., Methods: This single-center retrospective study included newly diagnosed children with eosinophilic (EoE) and non-eosinophilic (non-EoE) esophagitis based on endoscopic and histopathological results between January 2013 and December 2018., Result: Among 433 of enrolled children with esophagitis, 36 (8.31%) were diagnosed with EoE (median age of 10 years). Male predominance and an increased percentage of allergy cases in the EoE group were noticed. Dysphagia was the only symptom that significantly differentiated both groups ( p = 0.006). Endoscopic findings with relevant relationships with EoE included linear fissuring, decreased vascular pattern, trachealization and whitish exudates. No significant difference in the prevalence of other reported diseases between groups was observed., Conclusion: The results of EoE analysis in children from North-Eastern Poland did not differ from reports from other countries. The reported symptoms were not specific for EoE, and only dysphagia and some endoscopic lesions were helpful to differentiate children with EoE from non-EoE.

Background and Aims: Eosinophilic esophagitis (EoE) is a chronic, local immune-mediated esophageal disease with eosinophil-dominated inflammation. The incidence of the disease is rapidly increasing in both children and adults. The pathogenesis of the disease is still not well understood. We present a review of the literature devoted to the EoE immunopathology, in particular the markers of inflammation and epithelial integrity, and their usefulness in disease monitoring and therapy., Methods: We performed a systematic search of the MEDLINE/PubMed databases for studies to examine the use of immunohistochemistry as a diagnostic tool for EoE., Results: The gold standard of EoE diagnosis requires multiple endoscopies with biopsies for histological assessment. The minimum number of eosinophils evaluated in hematoxylin-eosin staining to diagnose EoE is 15 per high-power field in at least one esophageal mucosa biopsy. However, in some cases, the count of eosinophils is not specific and insufficient as the only indicator. Recent works confirm the usefulness of assessment of some biomarkers in establishing the diagnosis and monitoring the treatment effects., Conclusions: Immunohistochemistry seems to be a promising option not only in clinical recognition, but also in the selection and monitoring of treatment effects. However, these methods have not yet recommended for routine clinical use.

Competing Interests: All authors have disclosed no conflicts of interest.

Inflammatory bowel disease (IBD) diagnosis and therapy is challenging for every pediatrician, especially when complicated with extraintestinal manifestations. The article reviews current literature on the hepatobiliary manifestations associated with inflammatory bowel disease in the pediatric population., Competing Interests: The authors report no conflict of interest., (Copyright: © 2019 Clinical and Experimental Hepatology.)