Search

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.

Epidemiological studies have demonstrated a strong association between cigarette smoking (CS) and chronic pancreatitis (CP); however, the exact mechanisms of this phenomenon remains unknown. The authors have previously shown that increased Ras expression activates the NF-κB mediated pathway and promotes development of CP. However, it is unclear whether a similar phenomenon occurs in CS-induced CP. Therefore, the aim of the study was to determine whether CS increases the expression of K-Ras, and promotes the development of CP in mice exposed to repeated episodes of acute pancreatitis (AP).C57BL6/cmdb mice were exposed to CS or a sham treatment for 12 weeks. After one week of exposure, half of the animals from both groups were additionally subjected to repeated cerulein treatment (once a week, for 10 consecutive weeks) to mimic recurrent episodes of AP. Extension of pancreatic damage was determined histologically by HE and Trichrome staining. The expression of K-Ras protein and downstream components (NF-κB, Cox-2, TGF-β) was evaluated by immunohistochemistry.C57BL6/cmdb mice exposed to CS or cerulein alone did not develop any chronic pancreatic damage. However, concomitant treatment with both of these agents caused focal acinar atrophy, with slight intralobular and perivascular areas of fibrosis, and inflammatory cells infiltration resembling mild CP. Moreover, immunohistochemistry examinations revealed increased pancreatic expression of K-Ras and NF-κB only in mice treated both with CS and cerulein.CS promotes development of CP in mice exposed to repeated episodes of AP. This process may be, at least partially, related to increased expression of K-Ras and NF-κB protein.

BACKGROUND The COVID-19 pandemic affected many people worldwide, including those with chronic diseases. Our objective was to analyze its influence on medical care and the course of inflammatory bowel disease (IBD) in Poland. MATERIAL AND METHODS In 2021, 81 patients in Poland with IBD completed an original anonymous questionnaire about the impact of the COVID-19 pandemic on the course of their disease and mental status. The printed questionnaire was distributed to IBD patients treated at the Gastroenterology Outpatient Clinic of the University Clinical Hospital in Białystok, and an online questionnaire was sent to patients via social media. Statistical analysis was performed using the chi-squared test, with a significance level of P0.05. RESULTS The study group consisted of 46 women and 35 men with a mean age of 32.42 years. Fifty-nine patients had ulcerative colitis and 22 had Crohn disease. Patients reported significant deterioration in medication availability (50.62%) and restricted access to gastroenterology outpatient clinics (51.90%) (P0.05). Of patients who contracted COVID-19, 89.47% did not require hospitalization, 32.10% (26/81) were asymptomatic, mild, or moderate, despite immunosuppressive biological treatment (27.16%, 22/81), or steroids (18.52%, 15/81). Over 50% of respondents stated the pandemic negatively affected their mental state and 30% of them associated that with worsening IBD. CONCLUSIONS During the pandemic, respondents were mainly concerned with difficulties in accessing the gastroenterology clinic and limited drug availability. The pandemic negatively affected patients' mental state. In cases of COVID-19 disease, patients with IBD were mostly asymptomatic and did not require hospitalization, despite therapy affecting the immune system.

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.

(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.

To evaluate the usefulness of routinely measured biochemical and complete blood count parameters as potential markers of the severity of paediatric acute pancreatitis (AP).The retrospective study included children with AP hospitalised over a 3 years period. Demographic, clinical and laboratory data were collected.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: 13.5x10Severe 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.

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.We performed a systematic search of the MEDLINE/PubMed databases for studies to examine the use of immunohistochemistry as a diagnostic tool for EoE.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.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.

Background: Inflammatory bowel disease (IBD) in children is frequently associated with liver pathology manifested as transient elevation of liver enzymes or specified liver diseases. The aim of the study was to evaluate the prevalence and the type of liver pathology in children with IBD within 2 years’ follow-up after the IBD diagnosis. Methods: We retrospectively reviewed records of children with IBD. Liver pathology was defined as elevated activity of liver enzymes (alanine transaminase (ALT) and/or gamma-glutamyl transpeptidase (GGT)) and bilirubin concentration in serum and/or as pathological changes of the organ on imaging tests (abdominal ultrasound and/or magnetic resonance cholangiopancreatography) or on liver histology performed when indicated. Results: Liver pathology was detected in 21 from 119 children (18%), including 7 (17%) with Crohn’s disease (CD) and 14 (18%) with ulcerative colitis (UC). Specified diagnosis for liver abnormality was found in 14 of 21 children (67%), including primary sclerosing cholangitis (PSC, 19%), non-alcoholic fatty liver disease (NAFLD, 19%), autoimmune sclerosing cholangitis (ASC, 5%), autoimmune hepatitis (AIH, 5%), cholelithiasis (5%), drug-induced liver disease (9%) and viral infection (herpes simplex virus, 5%). Most patients manifested mild IBD or were in clinical remission at the time of liver pathology diagnosis. 14% of patients with liver disease (including only cases with PSC) were diagnosed before IBD, 33% at the same time, and 52% in the later period. Patients with the specified diagnosis of liver pathology were younger, had higher ALT activity and more often demonstrated liver abnormalities on imaging tests. UC patients with idiopathic elevation of liver enzymes had higher pediatric ulcerative colitis activity index scores compared to children with specified liver disease. Conclusions: Liver pathology was observed in a significant percentage of children with IBD in our study. The majority of cases of hepatobiliary abnormalities were detected after diagnosis of IBD; therefore, children with IBD should undergo routine monitoring of liver enzymes.

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.

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: 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 Metabolic profiling might be used to identify disease biomarkers. The aim of our study was to determine the usefulness of untargeted metabolomics analysis to detect differences in serum metabolites between newly diagnosed and untreated pediatric patients with Crohn's disease (CD) or ulcerative colitis (UC) in comparison with a control group (Ctr). Moreover, we investigated the potential of profiling metabolomics and inflammatory markers to improve the noninvasive diagnosis of CD and UC in children. Methods Metabolic fingerprinting of serum samples was estimated with liquid chromatography coupled with mass spectrometry in children with CD (n = 9; median age, 14 years), UC (n = 10; median age, 13.5 years), and controls (n = 10; median age, 12.5 years). Results The majority of chemically annotated metabolites belonged to phospholipids and were downregulated in CD and UC compared with the Ctr. Only 1 metabolite, lactosylceramide 18:1/16:0 (LacCer 18:1/16:0), significantly discriminated CD from UC patients. Interestingly, combining LacCer 18:1/16:0 with other inflammatory markers resulted in a significant increase in the area under the curve with the highest specificity and sensitivity. Conclusions Using serum untargeted metabolomics, we have shown that LacCer 18:1/16:0 is a very unique metabolite for CD patients.

Matrix Metaloproteinase-9 (MMP-9) and Tissue Inhibitor of Metaloproteinase-1 (TIMP-1), enzymes involved in tissue remodelling, have been previously reported to be overexpressed in the colonic mucosa of patients with Ulcerative colitis (UC). The aim of this study was to determine the relation of MMP-9 and TIMP-1 with UC phenotypes, the disease activity index and routinely tested inflammatory markers in newly diagnosed paediatric patients. The study group comprised 35 children diagnosed with UC and 20 control groups. Serum and faecal concentrations of MMP-9 and TIMP-1 were estimated using enzyme-like immunosorbent assay kits and correlated to the disease activity index (Paediatric Ulcerative Colitis Activity Index, PUCAI), UC phenotype (Paris Classification), inflammatory markers and endoscopic score (Mayo score). Children with UC presented with significantly higher serum and faecal concentrations of studied markers compared to the control group. Both serums, MMP-9 and TIMP-1, were higher in children with more extended and severe lesions in the colon. Furthermore, serum MMP-9 correlated with the Mayo score, Paris classification and C-reactive protein (CRP) levels. Serum TIMP-1 showed correlation with PUCAI, Paris Classification, CRP levels and the erythrocyte sedimentation rate. Serum and faecal levels of MMP-9 and TIMP-1 are useful in discriminating UC patients and non-invasive assessments of disease phenotypes. It seemed that simultaneous measurement of these proteins in combination with other common markers of inflammation could be applied in clinical practice.

Pancreatic ductal adenocarcinoma is one of the deadliest human neoplasms. Despite the development of new surgical and adjuvant therapies, the prognosis remains very poor, with the overall survival rate not exceeding 9%. There is now increasing evidence that the human microbiome, which is involved in many physiological functions, including the regulation of metabolic processes and the modulation of the immune system, is possibly linked to pancreatic oncogenesis. However, the exact mechanisms of action are poorly understood. Our review summarizes the current understanding of how the microbiome affects pancreatic cancer development and progression. We discuss potential pathways of microbe translocation to the pancreas, as well as the mechanism of their action. We describe the role of the microbiome as a potential marker of pancreatic cancer diagnosis, progression, and survival. Finally, we discuss the possibilities of modifying the microbiome to improve treatment effectiveness for this deadly disease.

It is known that certain patients with very early onset IBD (diagnosis before 6 years of age) have a higher possibility of immune deficiency with monogenetic aetiology. The growing prevalence of these types of disorders forces the gastroenterologist to gain some knowledge about the symptoms and further diagnostic management, which includes consultation with the clinical immunologist. The resemblance of the clinical manifestation of early-onset Crohn's disease with ulcerative colitis and high incidence rate of unclassified IBD suggests caution in IBD diagnosis in younger patients.

Background Cigarette smoke (CS) exerts protective effect against ulcerative colitis. The mechanism of this phenomenon remains unknown. One of the possible explanation by which CS exerts its anti-inflammatory action is modulation of immune system. Therefore, the aim of the study was to evaluate the effect of CS on the course of inflammation and subpopulations of lymphocytes in the blood and colon in mice with dextran sulfate sodium (DSS)-induced colitis. Methods C57BL6/cmdb mice were exposed to CS for 4 weeks. Colitis was induced with 3.5% DSS given for 10 days. Severity of colitis was determined by disease activity index (DAI), body weight changes, and macro- and microscopic characteristics of inflammation. Peripheral subpopulations of lymphocytes were assessed by flow cytometry (blood) or immunohistochemistry (colonic tissue). Results Mice treated with 3.5% DSS developed severe colitis with significantly decreased body weight, increased DAI, and macroscopic and histological features of colonic inflammation. These findings were diminished after concomitant exposure to CS. Mice exposed to DSS alone demonstrated significantly decreased percentage of total CD4+ cells (73.1 vs. 52%, p = 0.0007), accompanied by increase of CD8+ cells (18.4 vs. 39.5%, p = 0.0001). Concomitant CS exposure reversed inappropriate CD4+/CD8+ ratio both in the blood and colon and significantly increased B cell presence in the colon. Conclusions Our study has demonstrated that CS exposure decreases severity of DSS-induced colitis. This phenomenon was accompanied by changes in CD4/CD8 ratio and B cell level in the peripheral blood and colon. These mechanisms may be responsible for protective effect of smoking in ulcerative colitis. Electronic supplementary material The online version of this article (doi:10.1007/s00384-017-2882-9) contains supplementary material, which is available to authorized users.

Since Kupffer cells/macrophages (KCs/MPs) may be involved in the pathogenesis of autoimmune hepatitis (AIH), this pioneer study was undertaken to evaluate KCs/MPs in pediatric AIH in transmission-electron microscope. Methods Ultrastructural analyses were performed using liver biopsies from 14 children with clinicopathologically diagnosed AIH. Results In all AIH children, ultrastructural findings revealed changes in the cells lining sinusoidal vessels, especially KCs/MPs and endothelial cells. KCs/MPs showed increased phagocytic activity and damaged mitochondria, frequently with accompanying intense fibrosis. In 10/14 AIH patients, the cytoplasm of sinusoidal KCs/MPs contained characteristic glassy droplet inclusions. They were round, sharply circumscribed, and contained homogeneous material and distinct translucent fields. Their ultrastructure was identical with the Russel bodies of plasma cells, which were also found in liver biopsies in the same patients. Conclusion Ultrastructural identification of characteristic cytoplasmic droplets with glassy appearance in KCs/MPs, never before described in AIH, provides a useful novel morphological feature in the diagnosis of this 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

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.

Ulcerative colitis (UC) and Crohn's disease (CD) represent inflammatory bowel diseases (IBD) with multifactorial pathogenesis, involving genetic, environmental and microbial factors. Interactions between gut microbiota and immune system result in changes in metabolic pathways. Metabolomics is a comprehensive and quantitative (or semi-quantitative) analysis of metabolites synthetized in human's biological system. It has been shown that metabolic profiling might be used to identify disease biomarkers. Recent findings confirmed alterations in the number of metabolites in patients with IBD. However, most of the studies included adult individuals with ongoing treatment which might have affected the metabolite profiling. Therefore, the aim of our study was to collect the knowledge about metabolomics in paediatric patients with CD or UC based on the currently published literature.

BACKGROUND Changing the resources of vitamin D and antioxidant nutrients may affect the course of allergic diseases. The aim of the study was to investigate the association between CoQ10, vitamin D, retinol, and α-tocopherol serum levels and severity of atopic dermatitis (AD) in children. METHODS Twenty-nine children with AD aged from 1 to 15 years were enrolled into the study. The severity of AD was categorized into mild or moderate (≤50 points in SCORAD - Scoring Atopic Dermatitis index) and severe (>50 SCORAD points). The control group was comprised of 22 children with negative history of allergy aged from 2 to 15. The serum measurements included vitamin D, retinol, α-tocopherol, CoQ10, C-reactive protein (CRP), complete blood count (CBC), and total immunoglobulin E (IgE). RESULTS Low vitamin D concentration (

Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome and a risk factor for cardiovascular disease (CVD). Research conducted in adults has proven that GGT can also be an independent risk factor for CVD. The aim of this study was to ascertain if GGT can be regarded as a simple biomarker of cardiovascular risk in obese children with NAFLD. One hundred obese children, aged 7-17 years, with suspected liver pathology were admitted to our Department. Viral hepatitis and autoimmune, toxic and selected metabolic liver diseases were excluded. Anthropometry, laboratory tests, 1HMR spectroscopy and evaluation of the common carotid artery intima-media thickness (IMT) were performed in all subjects. NAFLD was confirmed in 38 obese patients. There was a significantly higher activity of GGT and ALT, the concentration of total and LDL cholesterol, waist circumference, left coronary artery IMT, mean IMT value and total lipids in 1HMRS in children with NAFLD in comparison to non-hepatopathic obese children. Logistic regression analysis indicated that GGT, total cholesterol, LDL-cholesterol, left IMT and waist circumference significantly affected the development of NAFLD in obese children. In ROC analysis only GGT, waist circumference and left IMT allowed to differentiate children with NAFLD from those without steatosis with GGT having the highest result (AUC=0.94). GGT activity in patients revealed weak or at the upper limit of statistical significance correlation with traditional cardiovascular risk factors: glucose level, waist circumference, BMI, total cholesterol, LDL-cholesterol and insulin level. This allows to suggest, that GGT might be a potential reliable, simple and non-invasive biochemical marker for estimation of cardiovascular risk in obese children with NAFLD. However, further studies on larger population are necessary to confirm that observation.

Purpose Increased fecal calprotectin is a sensitive marker of various types of intestinal inflammation. We investigated correlations between high fecal calprotectin concentration and serum inflammatory markers in children with different intestinal diseases with diarrhea with/without blood and/or abdominal pain, to test whether the combination of these markers can differentiate potential patients with inflammatory bowel disease. Materials/methods The study included 128 children with high fecal calprotectin concentration (>150ug/g) and symptoms suggesting bowel disorders, hospitalized in the years 2013– 2015. Twenty-six (20%) patients were diagnosed with Crohn’s disease, 55 (43%) with ulcerative colitis, 32 (25%) with intestinal infection and 15 (12%) with food protein induced proctocolitis. Results Significantly increased inflammatory markers were detected in children with inflammatory bowel disease, with a correlation between calprotectin and erythrocyte sedimentation rate – ESR (R = 0.53), mean corpuscular volume – MCV (R=-0.64), red blood cell distribution width (R = 0.56), albumin (R = −0.52), hemoglobin (R = −0.53) only in Crohn’s disease patients. To discriminate Crohn’s disease patients from patients with intestinal infection and patients with food protein induced proctocolitis, AUC analysis was performed. It revealed that considering ESR, CRP and albumin as additional markers to fecal calprotectin significantly improved diagnostic performance (AUC 0.917, p = 0.038). Conclusions In children with abdominal pain and/or diarrhea, increased ESR, CRP and decreased albumin combined with a high fecal calprotectin level yields additional diagnostic value in screening potential patients with Crohn’s disease. As far as differentiation of ulcerative colitis is concerned, low additional diagnostic value was found when high fecal calprotectin was combined with albumin.

Background and aim Antibiotics have many beneficial effects but their uncontrolled use may lead to increased risk of serious diseases in the future. Our hypothesis is that an early antibiotic exposition may affect immune system by altering gut microbiota. Therefore, the aim of the study was to determine the effect of penicillin treatment on gut microorganisms and immune system of mice. Methods 21-days old C57BL6/J/cmdb male mice were treated with low-dose of penicillin (study group) or water only (control group) for 4 weeks. Tissue and stool samples for histology or microbiome assessment and peripheral blood for CBC and flow cytometry evaluation were collected. Results We found high variability in microbiota composition at different taxonomic levels between littermate mice kept in the same conditions, independently of treatment regimen. Interestingly, low-dose of penicillin caused significant increase of Parabacteroides goldsteinii in stool and in colon tissue in comparison to control group (9.5% vs. 4.9%, p = 0.008 and 10.7% vs. 6.1%, p = 0.008, respectively). Moreover, mice treated with penicillin demonstrated significantly elevated percentage of B cells (median 10.5% vs 8.0%, p = 0.01) and decrease in the percentage of total CD4+ cell (median 75.4% vs 82.5%, p = 0.0039) with subsequent changes among subsets - increased percentage of regulatory T cells (Treg), T helper 1 (Th1) and T helper 2 (Th2) cells. Conclusion Our study showed significant effect of penicillin on B and T cells in peripheral blood of young mice. This effect may be mediated through changes in gut microbiota represented by the expansion of Parabacteroides goldsteinii.

Defective Fas signaling leads to resistance to various anticancer therapies. Presence of potential inhibitors of Fas which could block Fas signaling can explain cancer cells resistance to apoptosis. We identified promyelocytic leukemia protein (PML) as a Fas-interacting protein using mass spectrometry analysis. The function of PML is blocked by its dominant-negative form PML–retinoic acid receptor α (PMLRARα). We found PMLRARα interaction with Fas in acute promyelocytic leukemia (APL)–derived cells and APL primary cells, and PML-Fas complexes in normal tissues. Binding of PMLRARα to Fas was mapped to the B-box domain of PML moiety and death domain of Fas. PMLRARα blockage of Fas apoptosis was demonstrated in U937/PR9 cells, human APL cells and transgenic mouse APL cells, in which PMLRARα recruited c-FLIPL/S and excluded procaspase 8 from Fas death signaling complex. PMLRARα expression in mice protected the mice against a lethal dose of agonistic anti-Fas antibody (P < .001) and the protected tissues contained Fas-PMLRARα-cFLIP complexes. Taken together, PMLRARα binds to Fas and blocks Fas-mediated apoptosis in APL by forming an apoptotic inhibitory complex with c-FLIP. The presence of PML-Fas complexes across different tissues implicates that PML functions in apoptosis regulation and tumor suppression are mediated by direct interaction with Fas.

Gruźlica jelit jest chorobą rzadko rozpoznawaną w populacji pediatrycznej, jednak wobec narastającej liczby dzieci leczonych biologicznie (przeciwciała anty-TNF-α) z powodu nieswoistej choroby zapalnej jelit, istnieje zwiększone ryzyko reaktywacji zakażenia prątkiem. Podobieństwo obrazu klinicznego gruźlicy jelit i choroby Leśniowskiego-Crohna wymaga znajomości obrazu klinicznego oraz wiedzy o odmiennościach postępowania diagnostyczno-terapeutycznego w obu tych chorobach.

Background Long-term studies on the evolution of elevated total IgE (tIgE) concentration are in demand. Objective To investigate the prevalence of allergic diseases and influential factors in children with high tIgE levels during a 5-year period. Methods Children with high tIgE levels (>100 IU/mL) were study subjects. After the 5-year follow-up, an interview with the parents, clinical examination, and evaluation of tIgE and specific IgE (sIgE) to selected food and inhalant allergens were performed. Results The mean tIgE decreased significantly after 5 years in girls and boys regardless of the place of residence. Monosymptomatic patients accounted for most cases throughout the study, with the highest tIgE level at the beginning. After follow-up, the percentage of polysymptomatic patients increased. Their mean tIgE level was significantly higher than in the other groups. After follow-up, 11.7% of participants remained asymptomatic, and another 11.7% reported relief from symptoms. Allergy symptoms persisted in most children with normal tIgE levels. The 2-allergen sensitization was the most common through the study. Only patients sensitized to 4 allergens had unchanged levels of mean tIgE after follow-up and those with the highest mean tIgE level had a newly diagnosed sensitization to at least 1 allergen. A significant decrease of sIgE level was observed for food allergens. The values of sIgE to inhalant allergens even increased after the 5-year follow-up, despite decreased tIgE levels. Conclusion In children with allergy and an elevated concentration of tIgE, the increasing or stable value of tIgE could be a useful parameter for the prediction of the development of polysymptomatic allergy.

Uncontrolled proliferation of the cells and their resistance to programmed cell death are main features of malignant cells. The effectiveness in the treatment of cancers is based on the restoration of the sensitivity of transformed cells to apoptotic signals. Although significant progress has been made in this field during last decades, the resistance to chemotherapy becomes a problem in many cases. The association between cancer and modifiable health behaviors is well supported. At least one-half of all cancers are suggested to have a dietary component. Therefore many of the dietary agents and natural health products have attracted the attention of scientists. One of them is probiotics, the nonpathogenic microorganisms living in the intestinal tract which benefit the host. In human clinical trials, probiotics has been used successfully in the treatment of acute diarrhea. Other clinical indications for probiotics, mainly in inflammatory bowel disease, are still evaluated with promising preliminary data.

The development of the new techniques and methods enabled to investigate the role of duodenal reflux in the pathogenesis of gastroesophageal reflux disease (GERD) therefore there is a need to establish the most common symptoms occurring in patients with duodenal reflux.To determinate the type of manifestation and the prevalence of duodeno-gastroesophageal reflux in children and adolescents confirmed in Bilitec 2000 method.59 patients (37 girls, 22 boys) aged 7-17 years (mean 14.7) with the symptoms of GER there were divided into 2 groups: subgroups: A--18 children with confirmed duodeno-gastroesophageal reflux in Bilitec 2000TM method and B--control consisted of 15 children with short stature referred to endoscopy due to celiac disease exclusion. In accordance to the endoscopic finding there were selected 3 subgroups: 20 patients with duodenal reflux, 19 patients with esophagitis and 20 children presenting those both disorders simultaneously. In all patients from group B the endoscopy, Bilitec 2000 and esophagitis pH metric findings haven't showed any abnormality.The most common complain--in 16 (88.89%) patients was recurrent and/or chronic abdominal pain, next- heartburn in 12 (66.67%), vomits and/or regurgitations in 10 (55.56%) children.The clinical manifestation of duodenal reflux was very much alike as in acid gastroeophageal reflux in the examined group. Therefore the functional gastrointestinal tract examinations have to be included in the diagnostic procedure.

Food allergy is an abnormal response of the immunological system, especially of mucosal immunological system on antigens supplied per os. There are very complicated and still unexplained immunological mechanisms, which lead to hypersensitivity reaction. Most often food hypersensitivity is identified as the effect of atopy, which is connected with humoral response (specific IgE antibody). On the other hand cell immunological response are less investigated, however they can be very important, especially as a significant factor to initiate pathological allergic processes.To investigate, the usefulness of flow cytometry for estimation of specific sensitization of subpopulation of lymphocytes on food allergens in the allergy diagnosis.The investigations were performed on 60 children from 6 months to 5 years old: 20 children with CM A IgE dependent, 20 with CM A IgE independent and 20 healthy children. IgE total, sIgE, IgG, IgA, IgM, basic immunological panel, CD 23, CD25, CD26, CD30, CD69, PCNA were measured.We noticed decrease of expression of CD4+CD30+ between I and II examination (p=0.029), between I and III (p=0.009); decrease of expression of CD8+CD26+ between I and III test (p=0.038); decrease of expression of CD19+CD23+ between I and II examination (p=0.012) in I type of hypersensitivity. We observed a decrease of expression of CD4+CD25+ between I and III examine (p=0.026) and decrease of expression of CD4+ CD26+ between I and III examination (p=0.036) in IV type of hypersensitivity. Expression of CD69 was decreased after diet in IgE dependent allergy. Values of expression of PCNA are similar in I and IV type of hypersensitivity in children with CM A. Decrease of expression of PCNA in II examination was observed in both cases. Reintroduced allergen caused increase of expression of PCNA in both types of allergy (p=0.048 and p=0.041).Our recent research confirms changes of the expression of T lymphocytes activation markers. It is connected with in vivo stimulation to allergen or with allergen elimination. The study of expression of activation markers using flow cytometry in food allergy in children can be helpful in observation of the dynamic progress process, but it cannot be used as a single diagnosis test.

There is increasing evidence that both the prevalence and severity of atopic diseases are progressively increasing in developed countries. Similar trends are also observed in rural societies which are in the process of urbanization. If allergy is really malaise of modern society, what are the environmental and societal factors responsible for it's emergence? Authors discuss this problems underlining causative role of both factors in the development of allergic disease including food allergy.

Gastroesophageal reflux (GER) plays an important role in pathogenesis of recurrent/chronic disorders of the respiratory tract. Atypical symptoms of GER can be suggested to be cause of the otorhinolaryngological problems. For these last manifestations no cause-effect relationship has yet been proven. There are many therapeutic studies, in which treatment of GERD is examined for its impact on coexisting respiratory disorders. The aim of our study was to confirm the presence of acid reflux by using 24-hour intraesophageal pH monitoring. From the group of 29 patients with recurrent episodes of the pharyngitis, laryngitis and tracheitis, we evaluated 18 children aged 3 months to 8 years (mean, 4.23 +/- 2.85) with coexisting reflux symptoms. The protocol included a parenteral interview, physical examination, roentgenograms of the chest and larynx, laryngoscopy, as well as 24-hour simultaneous proximal and distal esophageal pH monitoring. The most significant differences between examined patients and control subjects was noted in terms of the lowest pH value, number of reflux episodes and index reflux while pH dropped below 4. Every significant drop under pH 6 recorded in proximal esophagus was simultaneous with reflux episode in distal esophagus. We found increased both sensitivity and specificity of the simultaneous pH monitoring in the distal and proximal part of the esophagus comparing to monitoring by the single probe. We confirmed the presence of gastroesophagopharyngeal reflux in patients with recurrent disorders of pharynx, larynx and/or trachea.

Bartter syndrome is an uncommon tubular disorder inherited as an autosomal recessive entity. It is associated with hypokalemic metabolic alkalosis with high renin and aldosterone plasma concentration with low or normal blood pressure. Recent studies have demonstrated genetic heterogeneity in Bartter syndrome. Mutations of two genes encoding the Na/K/2Cl cotransporter and potassium channel ROMK are responsible for clinical features of neonatal Bartter syndrome. Mutations of gen encoding the chloride channel ClC-Kb is identified as being causative for the classic Bartter syndrome. And dysfunction of Na/Cl cotransporter in the distal convoluted renal tubule is described as Gitelman syndrome.

The authors present the case of 4-month-old girl, who was admitted to our hospital with hypokalemia, metabolic alkalosis, hyperaldosteronism, hyperreninism with normal blood pressure and high urine concentration of PGE2. All the clinical and biochemical features have led to the diagnosis of Bartter syndrome. Treatment consisted of 15% KCI, spironolacton and indometacin.

The aim of the current study was to analyse selected parameters of pH monitoring in the proximal and distal parts of esophagus. One hundred and twelve infants aged 1.25 to 18 months (mean = 5.6) with symptoms and signs suggesting gastroesophageal reflux (GER) were evaluated. The results are presented of the measurement of reflux index (RI), the number of reflux episodes and the duration of the longest reflux episode in patients classified into the following groups: group I--39 children with vomiting/excessive regurgitation, group II--29 infants with persistent distress/inconsolable crying, group III--16 children with Apparent Life Threatening Events (ALTE), group IV--28 infants with chronic/recurrent respiratory system diseases. No statistically significant difference was noted between the groups in pH parameters at the distal esophageal level, whereas at the proximal level the differences included only the number of reflux episodes. However, we found, that by using the ANOVA test, the incidence was higher in group IV than in group II. As determined by applying Mann-Whitney rank sum test, reflux episodes occurred most frequently in group IV, than in other groups of patients (including controls). None of the reflux parameters recorded at the proximal level among children presenting with ALTE was statistically significantly different than in other groups.

Alkaptonuria is a rare metabolic condition caused by congenital homogentisate oxidase deficiency of recessive inheritance. Homogentisate polymers are accumulated and cause urine darkening, brown pigmentation of connective tissue, articular cartilage pathology. The authors present clinical picture, pathogenesis, diagnostic and therapeutic possibilities in patients with alkaptonuria. Two siblings with alkaptonuria are described.

Fas plays a critical role in cell proliferation and in the selective killing of autoreactive lymphocytes and abnormal cells, including infected cells. To explain the common expression of Fas and the resistance to the Fas-induced apoptosis observed in some normal and cancer cells, we have screened cells for potential regulators of the Fas death receptor. By using mass spectroscopy analysis of Fas-associated proteins, we identified peptides derived from promyelocytic leukemia (PML). PML enhances pro-apoptotic signaling, while the promyelocytic leukemia-retinoic acid receptor α (PMLRARα) activates pro-survival pathways. Given these opposing functions, we tested whether PMLRARα, which typically operates in a dominant-negative manner, blocks Fas-mediated apoptosis. Co-immunoprecipitation analysis demonstrated that PMLRARα interacts with Fas in acute promyelocytic leukemia (APL)-derived NB4 cells, U937-PR9 cells and in APL primary cells. The binding of PMLRARα to Fas was mapped to the B-box domain of PMLRARα. Flow cytometry analysis of propidium iodide-stained and Annexin-V-stained cells challenged with Fas ligand (FasL) or agonistic anti-Fas antibody (CH-11) indicated that the presence of PMLRARα was associated with blocked Fas-mediated apoptosis at early and late stages. The knockdown of PMLRARα with shRNA sensitized the NB4 cells to Fas-mediated apoptosis. Expression of PMLRARα in U937-PR9 cells prevented Fas-mediated cleavage of procaspase-8 and also prevented procaspase-8 from binding to the Fas complex upon stimulation with the agonistic anti-Fas antibody (CH-11). Further analysis indicated that PMLRARα bound to FLIPL/S and forms a complex with Fas associated with suppression of Fas signaling. These data suggest that cancer-specific inhibitors of Fas such as PMLRARα block Fas-mediated apoptosis and thus can contribute to cancer development and resistance to therapy. Our results may provide an explanation for the long-known role of PMLRARα and PML in the regulation of Fas signaling, which we have shown to occur by direct regulation. We have identified an attractive potential target to the regulation of apoptosis at the PMLRARα-Fas and PML-Fas interfaces. By neutralizing the effect of death receptor inhibitors such as PMLRARα and other potential inhibitors, we can improve on the success of the many chemotherapeutic treatments that depend on activation of death receptors for effective elimination of cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2908.