Biochemical and Anthropometric Indices of Insulin Resistance in Obese and Overweight Children with Metabolic Dysfunction-Associated Fatty Liver Disease.

BACKGROUND The prevalence of metabolic (dysfunction)-associated fatty liver disease (MAFLD) increases together with the epidemic of childhood obesity. An important mechanism in the phenomenon appears to be insulin resistance (IR), the assessment of which in children is problematic. The homeostatic model assessment of IR (HOMA-IR), commonly used for this, is not standardized and appears not to correlate with IR in the pediatric population. Therefore, our study aimed to evaluate potential substitute indices of IR, including the triglyceride-glucose index (TyG), triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), modified TyG indices: TyG-waist circumference (TyG-WC) and TyG-body mass index (TyG-BMI) as surrogate markers of MAFLD in obese children suspected to have liver disease. MATERIAL AND METHODS The retrospective study included 264 obese children admitted to the Department to diagnose suspected liver disease. MAFLD was diagnosed according to the International Expert Consensus Statement. Anthropometric measurements and laboratory tests were made and the indices were calculated. Receiver operating characteristics analysis was performed to calculate the power of the indices. RESULTS MAFLD was diagnosed in 184 patients (70%). Obese children with MAFLD showed significantly higher activity of liver enzymes and concentration of total cholesterol, TG, WC, and waist-to-hip ratio compared to non-hepatopathic obese controls (n=80). The most important indices in identifying MAFLD were: TyG (AUC=0.641, p<0.001, cut-off =8.41, sensitivity=57.4%, specificity=68.8%), and TG/HDL-C (AUC=0.638, p<0.001, cut-off=2.5, sensitivity=48.6%, specificity=76.3%). TyG-BMI and HOMA-IR were not useful predictors. CONCLUSIONS TyG and TG/HDL-C can be considered as potential surrogate biomarkers in predicting MAFLD in obese children.

Medical Misinformation in Polish on the World Wide Web During the COVID-19 Pandemic Period: Infodemiology Study.

BACKGROUND: Although researchers extensively study the rapid generation and spread of misinformation about the novel coronavirus during the pandemic, numerous other health-related topics are contaminating the internet with misinformation that have not received as much attention. OBJECTIVE: This study aims to gauge the reach of the most popular medical content on the World Wide Web, extending beyond the confines of the pandemic. We conducted evaluations of subject matter and credibility for the years 2021 and 2022, following the principles of evidence-based medicine with assessments performed by experienced clinicians. METHODS: We used 274 keywords to conduct web page searches through the BuzzSumo Enterprise Application. These keywords were chosen based on medical topics derived from surveys administered to medical practitioners. The search parameters were confined to 2 distinct date ranges: (1) January 1, 2021, to December 31, 2021; (2) January 1, 2022, to December 31, 2022. Our searches were specifically limited to web pages in the Polish language and filtered by the specified date ranges. The analysis encompassed 161 web pages retrieved in 2021 and 105 retrieved in 2022. Each web page underwent scrutiny by a seasoned doctor to assess its credibility, aligning with evidence-based medicine standards. Furthermore, we gathered data on social media engagements associated with the web pages, considering platforms such as Facebook, Pinterest, Reddit, and Twitter. RESULTS: In 2022, the prevalence of unreliable information related to COVID-19 saw a noteworthy decline compared to 2021. Specifically, the percentage of noncredible web pages discussing COVID-19 and general vaccinations decreased from 57% (43/76) to 24% (6/25) and 42% (10/25) to 30% (3/10), respectively. However, during the same period, there was a considerable uptick in the dissemination of untrustworthy content on social media pertaining to other medical topics. The percentage of noncredible web pages covering cholesterol, statins, and cardiology rose from 11% (3/28) to 26% (9/35) and from 18% (5/28) to 26% (6/23), respectively. CONCLUSIONS: Efforts undertaken during the COVID-19 pandemic to curb the dissemination of misinformation seem to have yielded positive results. Nevertheless, our analysis suggests that these interventions need to be consistently implemented across both established and emerging medical subjects. It appears that as interest in the pandemic waned, other topics gained prominence, essentially "filling the vacuum" and necessitating ongoing measures to address misinformation across a broader spectrum of health-related subjects.

Antibiotic-Resistant Strains of Helicobacter pylori in 50 Antibiotic Treatment-Naive Children in Northeast Poland Diagnosed by Gastric or Duodenal Biopsy Between February 2019 and May 2022.

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.

Unraveling the Interplay between Nonalcoholic Fatty Liver Disease and Polycystic Ovary Syndrome in Adolescents: Pathogenesis, Prevalence, and Management Strategies.

BACKGROUND With the expanding understanding of conditions contributing to heightened cardiovascular risk, emerging pathologies like nonalcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are being recognized as hepatic and ovarian manifestations of metabolic syndrome, respectively. This study aims to elucidate the recent advancements in our comprehension of the link between these conditions in the pediatric demographic, focusing on pathogenesis, incidence, diagnostic methods, and effective therapeutic strategies. MATERIAL AND METHODS A systematic review was conducted following the PRISMA 2020 guidelines, with a search of the PubMed database for eligible studies published in the ten years leading up to January 2023. RESULTS Out of 23 reports based on 16 original studies, we found a significantly higher prevalence of NAFLD in adolescents with PCOS compared to healthy controls. Factors such as increased de novo lipogenesis, alterations in gut microbiota, and a deficiency in growth differentiation factor-15 have been implicated in their pathogenesis. Additionally, novel biomarker S100A4, a clinical prediction score for hepatic steatosis in PCOS, and pharmacotherapy involving low-dose spironolactone, pioglitazone, and metformin have been proposed to enhance the management of these conditions. CONCLUSIONS A meticulous approach to the prevention, detection, and treatment of NAFLD in adolescents with PCOS is paramount to mitigate further complications. The study underlines the need for ongoing research to refine our understanding and management of these interconnected metabolic disorders.

Clinical Presentation and Co-Detection of Respiratory Pathogens in Children Under 5 Years with Non-COVID-19 Bacterial and Viral Respiratory Tract Infections: A Prospective Study in Bialystok, Poland (2021-2022).

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 Bialystok, 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.

Common variant p.D19H of the hepatobiliary sterol transporter ABCG8 increases the risk of gallstones in children.

INTRODUCTION: Gallstones are increasingly common in children. Genetic analyses of adult cohorts demonstrated that the sterol transporter ABCG8 p.D19H and Gilbert UGT1A1*28 variants enhance the odds of developing gallstones. The genetic background of common lithiasis in children remains unknown. METHODS: Overall, 214 children with gallstone disease (1 month-17 years, 107 boys) were inclueded. The control cohorts comprised 214 children (age 6-17 years, 115 boys) and 172 adults (age 40-92 years, 70 men) without gallstones. The ABCG8 p.D19H and UGT1A1*28 polymorphisms as well as ABCB4 (c.504C>T rs1202283, c.711A>T rs2109505) and NPC1L1 variants (p.V1296V rs217434, c.-18C>A rs41279633) were genotyped using TaqMan assays. Serum concentrations of plant sterols and cholesterol precursors were measured by gas chromatography/mass spectrometry. RESULTS: The ABCG8 risk allele was associated with an increased risk of stones (OR = 1.82, p = .03). Children carrying the p.19H allele presented with lower serum concentrations of surrogate markers of intestinal cholesterol absorption and decreased ratios of phytosterols to the cholesterol precursor desmosterol. Carriers of the common NPC1L1 rs217434 allele had an increased gallstone risk compared with stone-free adults (OR 1.90, p < .01). This variant also affected the ratio of phytosterols to cholesterol precursors (p = .03). Other tested variants were not associated with gallstone risk. CONCLUSIONS: The p.D19H ABCG8 and, to a lesser extent, NPC1L1 rs217434 variants increase the risk of early-onset gallstone formation. These results point to the presence of a common lithogenic pathway in children and adults.

The rs12532734 Polymorphism Near the Solute Carrier 26A3 Gene Locus Is Associated With Gallstone Disease in Children.

Gallstones are increasingly frequent in children. In this candidate gene study, we genotyped 5 gene variants ( ANO1 , SPTLC3 , TMEM147 , TNRC6B , rs12532734) from a recent gallstone genome-wide association study (GWAS) in a cohort of 214 children with gallstones and 172 gallstone-free adult controls. In total, 138 genotyped children presented with symptomatic gallstone disease, 47 underwent cholecystectomy, and 126 received ursodeoxycholic acid (UDCA) as therapy for stones. Among 5 tested variants, the rs12532734 polymorphism modulated the gallstone risk in the studied cohort. Its genotype distribution significantly ( P = 0.025) departed from the Hardy-Weinberg equilibrium among cases, and the common allele was associated with increased odds of developing gallstones at young age (OR = 1.69, P = 0.014). SLC26A3 is the nearest gene to rs12532734 and is involved in the transepithelial bicarbonate and chloride transport. The association of rs12532734 with pediatric gallstones is a novel finding warranting further investigations also with regard to biliary bicarbonate flux and bile composition.

The course of acute pancreatitis in children and potential simple laboratory markers of severity - A single Centre retrospective study.

AIM: To evaluate the usefulness of routinely measured biochemical and complete blood count parameters as potential markers of the severity of paediatric acute pancreatitis (AP). METHODS: The retrospective study included children with AP hospitalised over a 3 years period. Demographic, clinical and laboratory data were collected. RESULTS: In total, 55 patients were enrolled in the study. Mild AP was diagnosed in 45 children (82%), moderately severe in 7 (13%), and severe in 3 patients (5%). Together 10 children (18%) were categorised into a single severe group. Children with severe AP had higher white blood cell and platelet counts on admission as well as a C-reactive protein (CRP) concentration after 48 h. The CRP concentration after 48 h (cut-off: 127.2 mg/L) and the white blood cell count on admission (cut-off: 13.5x103 /µl) were found to be statistically significant markers in predicting the severity of the disease. The CRP concentration after 48 h was demonstrated as an independent predictor. CONCLUSION: Severe AP is observed in a quite significant percentage of children. The white blood cell count on admission and the CRP concentration after 48 h (as an independent predictor) may be potential simple laboratory markers of the severity of the disease.

The Etiology of Cholelithiasis in Children and Adolescents-A Literature Review.

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.

Autoimmune sclerosing cholangitis might be triggered by SARS-CoV-2 infection in a child - a case report.

The spectrum of liver involvement during coronavirus disease 2019 (COVID-19) is broad and mainly includes elevated liver enzymes and cholestasis. Severe acute respiratory syndrome corona- virus-2 (SARS-CoV-2) infection most often leads to a transient moderate increase in liver enzymes that is not accompanied by disturbances in the synthetic function of the liver. However, there is increasing evidence that SARS-CoV-2 infection is associated with the development of autoimmune disorders. The pathogenesis of autoimmune hepatobiliary diseases is not fully understood, taking into account genetic and environmental factors such as viral infections. We present a pediatric case of autoimmune sclerosing cholangitis (ASC), which was diagnosed 2 months after SARS-CoV-2 infection. To the best of our knowledge, ASC potentially triggered by COVID-19 has not been reported in pediatric patients. Further studies are needed to describe the clinical impact of the development of autoimmune liver diseases potentially associated with SARS-CoV-2 infection in pediatric patients. Our observations indicate that children with liver injury potentially caused by COVID-19 require long-term monitoring of liver function parameters.

The role of chemerin in the pathogenesis of cholelithiasis in children and adolescents.

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.

Nanomechanical Hallmarks of Helicobacter pylori Infection in Pediatric Patients.

BACKGROUND: the molecular mechanism of gastric cancer development related to Helicobacter pylori (H. pylori) infection has not been fully understood, and further studies are still needed. Information regarding nanomechanical aspects of pathophysiological events that occur during H. pylori infection can be crucial in the development of new prevention, treatment, and diagnostic measures against clinical consequences associated with H. pylori infection, including gastric ulcer, duodenal ulcer, and gastric cancer. METHODS: in this study, we assessed mechanical properties of children's healthy and H. pylori positive stomach tissues and the mechanical response of human gastric cells exposed to heat-treated H. pylori cells using atomic force microscopy (AFM NanoWizard 4 BioScience JPK Instruments Bruker). Elastic modulus (i.e., the Young's modulus) was derived from the Hertz-Sneddon model applied to force-indentation curves. Human tissue samples were evaluated using rapid urease tests to identify H. pylori positive samples, and the presence of H. pylori cells in those samples was confirmed using immunohistopathological staining. RESULTS AND CONCLUSION: collected data suggest that nanomechanical properties of infected tissue might be considered as markers indicated H. pylori presence since infected tissues are softer than uninfected ones. At the cellular level, this mechanical response is at least partially mediated by cell cytoskeleton remodeling indicating that gastric cells are able to tune their mechanical properties when subjected to the presence of H. pylori products. Persistent fluctuations of tissue mechanical properties in response to H. pylori infection might, in the long-term, promote induction of cancer development.

Pancreatic Disorders in Children with Inflammatory Bowel Disease.

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.

Diagnosis of autoimmune neutropenia in a 10-month-old boy - a case report.

Neutropenia, congenital or acquired, is related to impaired granulocyte production in the bone marrow or increased destruction by antibodies. Autoimmune neutropenia of infancy (AIN) is associated with the occurrence of antineutrophil antibodies. AIN is the most common cause of neutropenia in infants and young children. However, its incidence is low. Detection of anti-neutrophil antibodies is an important step in confirming the diagnosis of AIN, although their detection is difficult due to low titer and poor avidity. In differential diagnosis, another cause of neutropenia should be considered, such as a drug-induced mechanism, viral infection, autoimmune and metabolic disease, hematological conditions or immune deficiency syndromes. Despite the benign course of AIN, serious infectious complications can occur. Spontaneous remission of neutropenia was observed in 95% of patients during 24 months of follow-up. We present a case of a 10-month-old boy with deafness, heart defect and Morgagni-Larrey hernia diagnosed in our department because of formation of a skin abscess due to autoimmune neutropenia.

Pollen-related food allergy in children with seasonal allergic rhinitis.

INTRODUCTION: Seasonal allergic rhinitis (SAR) and bronchial asthma are typical manifestations of pollen-food sensitization in adults. There is limited information regarding the sensitization patterns of pollen-food allergy in children. AIM: To evaluate the prevalence of SAR in children with pollen-food sensitization and assess the impact of food allergens on nasal symptoms. MATERIAL AND METHODS: Forty-three children with pollen-food sensitization aged 2-14 years were evaluated for evidence of SAR. The inclusion criteria was IgE-mediated sensitization to pollen and homologous food allergens. The control group consisted of 19 children with SAR caused by pollen without sensitization to homologous food allergens. RESULTS: Allergic rhinitis was the main symptom in 65.1% of children; in 25.6% an association between ingestion of pollen-related foods and nasal symptoms was observed. The simultaneous sensitization to animal origin food allergens was stated in 63.3% of children with SAR. In 25.6% anaphylactic reactions to foods were registered. 37.2% of children were asymptomatic to pollen origin foods despite pollen-food sensitization. The statistically significant differences between values were noticed in comparison to the control group. CONCLUSIONS: Allergic rhinitis is a common manifestation of pollen-food sensitization in children and this type of immunological hyperreactivity should be taken into account regardless of age. The lack of association of symptoms with plant origin foods in the majority of cases and the asymptomatic course of food sensitization in more than one third of patients indicates the need for follow-up and being careful in routine recommending the avoidance diet.

Immunohistochemical markers for eosinophilic esophagitis.

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.

Usefulness of metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in clinical characterisation of children with newly diagnosed Crohn's disease.

AIM: The aim of this study was to determine the relation of non-invasive markers representing gut mucosal damage (metalloproteinase-9 (MMP-9)) and remodelling (tissue inhibitor of metalloproteinase-1 (TIMP-1)) with Crohn's disease (CD) phenotype, disease activity scores (clinical and endoscopic) and radiological evaluation of the ileum in newly diagnosed children. METHODS: Serum and faecal MMP-9 and TIMP-1 concentrations were determined with the sandwich enzyme-linked immunoassay technique. The performance of each marker with reference to the Paris classification, disease activity scores and magnetic resonance enterography results was assessed using non-parametric tests. RESULTS: A total of 32 children with CD demonstrated higher levels of serum and faecal MMP-9 and TIMP-1 compared with a control group including children without gastrointestinal inflammatory disease (all P < 0.05). Only the serum MMP-9 concentration was significantly higher in children with L3 (ileocolonic) compared with children with L1 (distal ileum). The serum TIMP-1 level was significantly higher in patients with an magnetic resonance enterography-detected ileum involvement longer than 51 mm and in children with severe disease activity compared with other patients. The serum MMP-9 level was lower in patients with stenosis combined with prestenotic dilation compared with children without stenosis. CONCLUSION: Increased serum and faecal MMP-9 and TIMP-1 concentrations are some reliable markers of inflammation in newly diagnosed children with CD, but without facilitating clear phenotyping of the disease.

Production and Use of Recombinant Profilins Amb a 8, Art v 4, Bet v 2, and Phl p 12 for Allergenic Sensitization Studies.

Four recombinant (r) allergens (rAmb a 8.0101, rArt v 4.0101, rBet v 2.0101, and rPhl p 12.0101) were successfully produced and used for sensitization studies. The allergens belong to the profilin family which is one of the most numerous allergen families. These four proteins represent allergens originating from pollen of weeds (rAmb a 8.0101 and rArt v 4.0101), tree (rBet v 2.0101) and grass (rPhl p 12.0101). The recombinant allergens were characterized using various biochemical and biophysical methods and tested for their ability to bind patient-derived antibodies. One hundred patients aged 2 to 50 years sensitized to pollen and plant-derived food allergens (IgE > 0.35 kU/L) were included. Sensitization to individual allergen sources and components of birch and timothy pollens was evaluated using multiparameter immunoblots. The presence of IgE to pollen-derived recombinant profilins rAmb a 8.0101, rArt v 4.0101, rBet v 2.0101, and rPhl p 12.0101 in serum was evaluated using ELISA method. The presence of IgE against pollen profilins was detected in 20 out of 100 studied patients. High correlation was seen between IgE ELISA results with individual pollen profilins. In summary, it was shown that the recombinant versions of the four allergenic profilins can be used for sensitization studies and for component-resolved allergy diagnostics.

PEG 3350 Versus Lactulose for Treatment of Functional Constipation in Children: Randomized Study.

OBJECTIVES: The aim of this study was to compare the clinical efficacy and tolerance of polyethylene glycol 3350 (PEG) and lactulose for the treatment of functional constipation in infants and children. METHODS: This randomized, multicenter study covered 12 weeks of treatment and 4 weeks of follow-up of patients with functional constipation. Patients were randomized (central randomization) to receive either PEG or lactulose. The primary end points were the number of defecations per week after 12 weeks of treatment and improvement in stool consistency of at least 2 points in the Bristol scale. The secondary end point was the presence of adverse events. Bowel movements ≥3 per week and stool consistency ≥2 (Bristol scale) were considered as successful treatment. RESULTS: We enrolled 102 patients (M 57, F 45) aged 3.62 ±â€Š1.42 years and 88 completed the study. At week 12, good clinical outcome was achieved in 98% (PEG) and 90% (lactulose). The PEG group had more defecations per week compared with the lactulose group (7.9 ±â€Š0.6 vs 5.7 ±â€Š0.5, P = 0.008) and both groups had similar frequency of defecation with pain (5% vs 5%, P = 0.9), stool retention (7% vs 10%, P = 057), large volume of stools (30% vs 31%, P = 0.9) and hard stools (7% vs 13%, P = 0.58). There were more patients with side effects in the lactulose group (15 vs 23, P = 0.02), mostly bloating and abdominal pain. CONCLUSIONS: PEG 3350 is more effective and causes fewer side effects than lactulose in the treatment of constipation in infants and children.

Increased serum concentration of ceramides in obese children with nonalcoholic fatty liver disease.

BACKGROUND: Hepatic lipid accumulation is closely related to the development of insulin resistance, which is regarded as one of the most significant risk factors of nonalcoholic fatty liver disease (NAFLD). Although the exact molecular pathway leading to impaired insulin signaling has not been definitively established, ceramides are suspected mediators of lipid induced hepatic insulin resistance. Therefore, the aim of the study was to evaluate the serum ceramides concentration in obese children with NAFLD. METHODS: The prospective study included 80 obese children (aged 7-17 years, median 12 years) admitted to our Department to diagnose initially suspected liver disease. Patients with viral hepatitis (HCV, HBV, CMV), autoimmune (AIH), toxic and metabolic (Wilson's disease, alfa-1-antitrypsin deficiency) liver diseases and celiac disease were excluded. NAFLD was diagnosed based on pediatric diagnostic criteria in obese children with liver steatosis in ultrasound (US) as well as elevated alanine transaminase (ALT) serum activity after exclusion of other major liver diseases listed before. Ultrasonography was used as a screening method and for qualitative assessment of the steatosis degree (graded according to Saverymuttu scale). Advanced steatosis was defined as a score > 1. The total intrahepatic lipid content (TILC) was assessed by magnetic resonance proton spectroscopy (1HMRS) which is the most accurate technique for assessment of ectopic fat accumulation. Fasting serum concentration of ceramides was measured in 62 children. RESULTS: NAFLD was diagnosed in 31 children. Significant, positive correlation was found between total serum concentration of ceramides and insulin (r = 0.3, p = 0.02) and HOMA-IR (r = 0.28, p = 0.03). Total ceramide concentration as well as specific fatty acid-ceramides (FA-ceramides) concentrations, namely: myristic, palmitic, palmitoleic, stearic, oleic, behenic and lignoceric were significantly higher (p = 0.004, p = 0.003, p = 0.007, p < 0.001, p = 0.035, p = 0.008, p = 0.003, p = 0.006, respectively) in children with NAFLD compared to controls (n = 14). Moreover, children with NAFLD had significantly higher activity of ALT (p < 0.001) and GGT (p < 0.001), HOMA-IR (p = 0.04), BMI (p = 0.046), waist circumference (p = 0.01) steatosis grade in ultrasound (p < 0.001) and TILC in 1HMRS (p < 0.001) compared to children without NAFLD. We did not find significant differences in total and FA-ceramide species concentrations between children with mild (grade 1) and advanced liver steatosis in ultrasonography (grade 2-3). CONCLUSION: Elevated ceramide concentrations in obese patients together with their significant correlation with insulin resistance parameters suggest their association with molecular pathways involved in insulin signaling impairment known to be strongly linked to pathogenesis of non-alcoholic fatty liver disease.