C-Reactive Protein/Albumin Ratio at Diagnosis of Pediatric Inflammatory Bowel Disease: A Retrospective Multi-Center Study.

BACKGROUND This study aimed to evaluate the C-reactive protein-to-albumin (CRP/albumin) ratio at diagnosis of pediatric inflammatory bowel disease (IBD). MATERIAL AND METHODS Serum CRP/albumin ratio was calculated for patients with Crohn's disease (CD; n=186) and ulcerative colitis (UC; n=159) aged 3-18 years. RESULTS Patients with CD differed in CRP/albumin ratio at diagnosis in groups with quiescent, mild, moderate, and severe disease (P=0.011). CRP/albumin ratio at diagnosis was significant in differentiating patients with severe CD from quiescent disease at diagnosis (area under the curve (AUC)=0.94, odds ratio (OR)=63.4, 95% confidence interval (CI) 7.1-569.1, P<0.0001). CRP/albumin ratio at diagnosis could moderately differentiate penetrating from non-penetrating disease behavior in CD at diagnosis (AUC=0.73, OR=6.3, 95% CI 2.0-19.3, P<0.001). Furthermore, CRP/albumin ratio at diagnosis weakly differentiated IBD patients in need of biological treatment in a step-up procedure (AUC=0.58, OR=2.1, 95% CI 1.3-3.4, P=0.022) and in need of surgery (AUC=0.63, OR=3.1, 95% CI 1.4-7.2, P=0.006). For the IBD, CRP/albumin ratio at diagnosis was weakly correlated with age at first immunosuppressive treatment (rho=0.20, P=0.018), time from diagnosis to first biological treatment (rho=-0.37, P<0.001), days spent in hospital (rho=0.26, P=0.007), number of severe relapses (rho=0.31, P=0.001), and Pediatric Crohn's Disease Activity Index (rho=0.38, P=0.002). CONCLUSIONS The present findings add to previous studies carried out in adult patients and show that the CRP/albumin ratio at diagnosis was not significantly associated with the course of either CD or UC in children. However, CRP/albumin ratio could differentiate patients with severe CD from those with quiescent disease.

No association between Helicobacter pylori infection and gastrointestinal complaints in a large cohort of symptomatic children.

AIM: This Polish study estimated the prevalence of the Helicobacter pylori infection in symptomatic children aged 3-18 and investigated its association with gastrointestinal complaints. METHODS: We prospectively enrolled 1984 children (54% female) with a mean age of 9.5 ± 4.1 years, from Silesia, Poland, for the Good Diagnosis Treatment Life screening programme from 2009 to 2016. They underwent a 13 C-isotope-labelled urea breath test (UBT) to assess their Helicobacter pylori status, making this the biggest Polish study to use this approach. Further analysis included parental-reported gastrointestinal symptoms and standard deviation scores (SDS) of anthropometric measurements. RESULTS: The Helicobacter pylori infection was identified in 220 (11%) children (48% female) and was independent of age and sex. The frequency of symptoms did not differ between Helicobacter positive and negative children (all p > 0.05). Children with a positive UBT result had a lower body mass SDS (-0.41 ± 0.98 versus -0.26 ± 1.01, p = 0.04) and height SDS (-0.45 ± 1.34 versus -0.23 ± 1.27, p = 0.02), but similar body mass index SDS. CONCLUSION: We found a low prevalence of Helicobacter pylori in symptomatic children, and positive UBT results were not associated with symptoms that suggested Helicobacter pylori infections. Our findings support the 2017 European and North American guidelines for Helicobacter infections in children.

Breath test using 13C methacetin does not seem to be useful in the assessment of liver function in girls with anorexia nervosa: a case control study.

BACKGROUND: Anorexia nervosa (AN) concerns approximately up to 1.8% of the pediatric female population. One of the complications that can occur in the course of this disease is acute liver failure. This study's objective was to assess the usefulness of the 13C labeled Methacetin Breath Test (MBT) in the diagnostics of the liver function in girls with eating disorders. METHODS: For the study 81 girls aged 12 to 17 years were recruited, including 41 patients with confirmed diagnosis of AN (mean age 14.7 ± 1.48 years) and 40 age-matched controls. The diagnosis was based on the present Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. Weight and height were measured in all study participants and the Body Mass Index (BMI) was calculated. In the study and control group laboratory tests assessing the liver function and the MBT were performed. RESULTS: In all controls the anthropometric as well as laboratory liver function parameters were normal. In the study group 25 patients (61%) had BMI below the lower limit for age. The total percentage of 13CO2 recovery in the 120th minute of the test did not exceed the lower limit in patients and controls. A result of the 13CO2 cumulative recovery above the upper normal range was found in 18 girls with AN (44% of the study group) and 2 controls (5%). Patients with AN were characterized by significantly higher 13CO2 cumulative dose recovery after ingestion of the substrate in comparison to the control group in all time points of the test. CONCLUSIONS: The obtained results confirm a significant stimulation of the liver metabolism of 13C labeled methacetin in female patients with AN. The increased cumulative dose recovery of the substrate in girls with AN impacts the credibility of this measurement and implies a risk of false negative results.

Helicobacter pylori infection in type 1 diabetes children and adolescents using 13C urea breath test.

There is a 10-30% prevalence of HP infection in the general pediatric population in Poland. This study aimed to determine its prevalence in T1DM children in Upper Silesia, Poland and estimate its influence on metabolic control of patients. We studied 149 (82 female) children with T1DM (duration > 12 months, mean HbA1c) and 298 (164 female) age-matched controls. In all cases height and weight z-scores and Cole's index were assessed. In T1DM patients additionally glycated hemoglobin A1c and T1DM duration were analyzed. Presence of HP infection was determined using 13C-isotope-labeled urea breath test (UBT) (fasting and 30 min after ingestion 75 mg of 13C urea). HP infection was present in 17 (11.4%) T1DM patients and in 49 (16.4%) controls (p > 0.05). T1DM patients presented higher values of anthropometric parameters than healthy controls (weight SDS 0.25[-0.46 divided by 0.84] vs. -0.25 [-1.06 divided by 0.26], height SDS 0.09 [-0.60 divided by 0.69] vs. -0.31[-1.17 divided by 0.48] and Cole's index 103% [93 divided by 111%] vs. 97% [86 divided by 106%]; for all p < 0001). Within both groups--T1DM children and controls--no differences regarding sex, age and any of the anthropometric parameters were determined. T1DM duration and HbA1c showed no relation to prevalence of HP infection. Prevalence of HP infection in pediatric T1DM patients is similar to that of healthy peers and shows no relation to glycemic control.

[Biological treatment of inflammatory bowel diseases in children in the years 2004-2013 in Poland]. / Leczenie biologiczne nieswoistych zapalen jelit u dzieci w latach 2004-2013 w Polsce.

UNLABELLED: In the last years an increase in Crohn's disease morbidity in children is observed together with constant morbidity of ulcerative colitis. The course of these diseases is severe, younger children are affected and the diseases are resistant to conventional treatment. Biological drugs are a chance for a longer remission and healing of the intestinal mucosa. OBJECTIVE OF THE WORK: Assessment of the use of biological drugs in treatment of inflammatory bowel disease in Poland was the objective of the work. MATERIAL AND METHODS: Gastroenterological centers treating inflammatory bowel disease during the years 2004-2013 were invited to a questionnaire retrospective study. RESULTS: The questionnaires of biological treatment of Crohn's disease and ulcerative colitis in children were received from 12 centers. In the years 2004-2013 the number of children aged 4 months to 18 years with Crohn's disease treated with biological drugs was 424. In the years 2004-2008--69 children were treated with infliximab and in the years 2009-2013--299 children, which was a four-fold increase. 56 children were treated with adalimumab in the years 2008-2013. In the years 2005-2013--72 children with ulcerative colitis were treated with infliximab and 11 with adalimumab. The age of the children ranged from 2 years to 18 years. The higher number of children treated was in the years 2009-2013: 59 with infliximab and 10 with adalimumab. CONCLUSIONS: In the last decade a significant increase on the number of children with Crohn's disease and ulcerative colitis treated with biological drugs was observed. It is connected not only to greater morbidity but above all to the introduction of a treatment program by the National Health Insurance Fund for children with Crohn's disease. There is an expectation that the introduction of biological treatment in inflammatory bowel disease will prolong clinical and endoscopic remission and diminish the number of surgeries.

Postprandial Abdominal Pain Caused by Gastroptosis-A Case Report.

Gastroptosis is a condition in which the stomach is displaced downward and is a condition affects the spontaneous muscle mobility in the stomach. The reason for its current prevalence remains unclear as the medical literature is scarce on the condition in children. In this study, we describe the case of a 17-year-old girl suffering from chronic, position-dependent epigastric pain. The symptoms were observed during post-meal activity, with a significant increase in pain intensity while in an upright position. An inferior stomach displacement was noted in an upper gastrointestinal X-ray study using barium.

Methylation of RUNX3 Promoter 2 in the Whole Blood of Children with Ulcerative Colitis.

Ulcerative colitis (UC) results from a complex interplay between the environment, gut microbiota, host genetics, and immunity. Runt-related transcription factor 3 (RUNX3) regulates Th1/Th2 balance and, thus, the synthesis of cytokines and inflammation. We aimed to analyze the dependence of RUNX3 promoter 2 (P2) methylation level on: age, sex, body mass index (BMI), C-reactive protein (CRP), serum albumin, disease duration, Pediatric Ulcerative Colitis Activity Index (PUCAI), the Paris classification, and exposure to medications. This multicenter, cross-sectional study recruited hospitalized children with UC. Methylation of RUNX3 P2 was measured with methylation-sensitive restriction enzymes in the whole blood DNA. Sixty-four children were enrolled, with a mean age of 14.5 ± 2.8 years. Half of them were female (51.6%), and the average BMI Z-score was -0.44 ± 1.14. The mean methylation of RUNX3 P2 was 54.1 ± 13.3%. The methylation level of RUNX3 P2 did not correlate with age, sex, nutritional status, CRP, albumin, PUCAI, or the extent of colitis (Paris E1-E4). RUNX3 P2 methylation did not differ between patients recruited within two and a half months of diagnosis and children who had UC for at least a year. Current or past exposure to biologics, immunosuppressants, or steroids was not associated with RUNX3 P2 methylation. Methylation of RUNX3 promoter 2 in whole blood DNA does not seem to be associated with the characteristics of UC in children.

Clinical features of asthma in children differ with regard to the intensity of distal gastroesophageal acid reflux.

BACKGROUND: The prevalence of gastroesophageal reflux (GER) in children with asthma is higher than in healthy controls, but the nature and direction of this association is unclear. OBJECTIVE: The aim of our study was to assess the relationship between esophageal acid exposure and the clinical features of asthma in children. METHODS: In total, 66 children (mean age 122.8 months [SD 44.89 months]) with chronic pulmonary symptoms, fulfilling diagnostic criteria of persistent asthma, underwent 24-hour esophageal pH monitoring and answered a detailed questionnaire-based survey. The questionnaire topics included environmental factors, familial history, current and previous clinical symptoms, atopy, asthma severity, and medication. RESULTS: Abnormal results of 24-hour esophageal pH monitoring were found in 28 out of 66 children (42.4%). Age, sex, severity of asthma, environmental factors, spirometry results, and the type of medication did not correlate with esophageal acid exposure. However, children with abnormal pH results developed asthma significantly earlier (asthma onset 3.63 years [SD 2.52 years] vs 5.77 years [SD 3.82 years]; p < .01). Nonatopic individuals had more intensive esophageal acid exposure than atopic ones (Boix-Ochoa score 28.19 [SD 18.26] vs 18.26 [SD 12.84]; p < .048). The intensity of GER was also significantly correlated with frequent or difficult-to-control nighttime asthma attacks. CONCLUSIONS: There are differences in clinical features of asthma in children with regard to the intensity of esophageal acid exposure. Symptoms of asthma in nonatopic individuals with early onset and difficult-to-control nighttime asthma attacks suggest the possibility of concomitant, clinically relevant GER.

Usefulness of Measuring Thiopurine Metabolites in Children with Inflammatory Bowel Disease and Autoimmunological Hepatitis, Treated with Azathioprine.

INTRODUCTION: Thiopurines, such as azathioprine (AZA) and 6-mercaptopurine (6-MP), are immunomodulatory agents, used for the maintenance of remission in children with inflammatory bowel disease (IBD)-Crohn's disease (CD) and ulcerative colitis (UC), as well as with autoimmunological hepatitis (AIH). Measurements of thiopurine metabolites may allow identifying patients at risk for toxicity and nonadherence. It can also provide an explanation for the ineffectiveness of the treatment, observed in some patients. Patients and Methods. A retrospective analysis was carried out of sixty-eight patients (thirty-six patients with CD, eighteen with UC, and fourteen with AIH), treated with AZA. Thiopurine metabolites, 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP), were assayed by high-performance liquid chromatography (HPLC), and the AZA dose was adjusted when 6-TGN concentration was known. RESULT: Only twenty-five (41%) children had therapeutic 6-TGN concentrations, ten (16%) subjects had suboptimal 6-TGN concentrations, and twenty-six subjects (43%) had 6-TGN concentrations above the recommended therapeutic range. 6-MMP was not above the therapeutic range in any case. Seven subjects revealed undetectable 6-TGN and 6-MMP levels, indicating nonadherence. The mean AZA dose after the 6-TGN concentration-related adjustment did not differ, in comparison to the initial dose, either in IBD or AIH groups. The mean AZA dose was lower in AIH than in IBD. The subjects with an optimal 6-TGN level presented with a higher ratio of remission (88%) than the under- or overdosed patients (60% and 69%), respectively (Chi - square test = 3.87, p < 0.05). CONCLUSION: Timely measurements of thiopurine metabolites can be a useful tool to identify nonadherent patients before a decision is taken to switch to another drug. We may also spot the patients who receive either too low or too high doses, compensating dose deviations in an appropriate way. The patients with optimal 6-TGN levels presented a higher percentage of remission than the under- or overdosed patients. In most patients, both initial and adjusted AZA doses, lower than suggested in guidelines, appeared to be sufficient to maintain remission.

Exocrine Pancreatic Function in Girls with Anorexia Nervosa.

OBJECTIVES: To assess pancreatic exocrine function in patients with anorexia nervosa using a breath test with 13C-labeled mixed triglycerides (MTG-BT) and to determine the relationship between the test results and selected biochemical and hormonal parameters. MATERIAL AND METHODS: Anthropometric measurements, biochemical and hormonal parameters (serum leptin, soluble leptin receptor (sLR), acylated and desacylated ghrelin, free leptin index (FLI)), and MTG-BT were performed in a group of 31 girls with the restrictive type of AN, as well as 38 healthy girls (C). RESULTS: The average cumulative dose of 13C-triglycerides recovered with exhaled air (%CD) was similar in both study groups, while the average time from 13C-triglycerides administration to peak 13CO2 excretion in expired air (time to peak (TTP)) was significantly longer in patients with AN compared to C. In both groups, %CD correlated negatively with FLI. TTP correlated negatively with sLR and FLI in the AN and with serum insulin and HOMA-IR values in the C. CONCLUSIONS: In girls with AN, the pancreatic efficiency of lipase secretion was found to be normal, while the kinetics of this enzyme secretion were disturbed. These changes may result from disorders in the functioning of the adipose-insular and islet-acinar axes.

No Correlation between Positive Fructose Hydrogen Breath Test and Clinical Symptoms in Children with Functional Gastrointestinal Disorders: A Retrospective Single-Centre Study.

Fructose malabsorption is regarded as one of the most common types of sugar intolerance. However, the correlation between gastrointestinal symptoms and positive results in fructose hydrogen breath tests (HBTs) remains unclear. The aim of this study was to assess the clinical importance of positive fructose HBT by correlating the HBT results with clinical features in children with various gastrointestinal symptoms. Clinical features and fructose HBT results were obtained from 323 consecutive children (2-18 years old, mean 10.7 ± 4.3 years) that were referred to the Tertiary Paediatric Gastroenterology Centre and diagnosed as having functional gastrointestinal disorders. A total of 114 out of 323 children (35.3%) had positive HBT results, of which 61 patients were females (53.5%) and 53 were males (46.5%). Children with positive HBT were significantly younger than children with negative HBT (9.0 vs. 11.6 years old; p < 0.001). The most frequent symptom among children with fructose malabsorption was recurrent abdominal pain (89.5%). Other important symptoms were diarrhoea, nausea, vomiting, and flatulence. However, no correlation between positive fructose HBT results and any of the reported symptoms or general clinical features was found. In conclusion, positive fructose HBT in children with functional gastrointestinal disorders can be attributed to their younger age but not to some peculiar clinical feature of the disease.

Subjective Psychophysical Experiences in the Course of Inflammatory Bowel Disease-A Comparative Analysis Based on the Polish Pediatric Crohn's and Colitis Cohort (POCOCO).

No gold standard is available to evaluate subjective psychophysical experiences in pediatric inflammatory bowel disease (IBD). We aimed to assess pain, anxiety, and limitations in social activities at diagnosis and the worst flare of the disease in relation to clinical expression, treatment and IBD severity. A total of 376 children completed the survey (Crohn's disease (CD) n = 196; ulcerative colitis (UC) n = 180). The questionnaire included 12 questions regarding pain, anxiety, and social activity, all assessed at recruitment and retrospectively at diagnosis and worst flare using a numeric rating scale. Patients that had ever been treated with systemic glucocorticosteroids scored higher in pain (p < 0.001), anxiety (p = 0.015), and social activity domains (p < 0.016) at worst flare, and the answers correlated with the number of steroid courses (p < 0.0392). The perception of social activity limitations also correlated independently with the number of immunosuppressants (p < 0.0433) and biological agents (p < 0.0494). There was no difference in retrospective perception of pain, anxiety and social activity limitations between CD and UC patients at diagnosis and the worst flare. The level of limitations in social activity correlated with hospitalisations due to relapse, days spent in the hospital, number of relapses, and severe relapses with the strongest association of rho = 0.39 (p = 0.0004). Subjective and retrospective perception of pain, anxiety, and limitations in social activity differs depending on therapy, correlates with treatment modalities, and severity measures such as hospitalisations.

HLA-DQA1*05 Associates with Extensive Ulcerative Colitis at Diagnosis: An Observational Study in Children.

The human leukocyte antigen (HLA) allele group HLA-DQA1*05 predisposes to ulcerative colitis (UC) and is associated with the development of antibodies against infliximab in patients with inflammatory bowel disease (IBD). Therefore, we hypothesized that the presence of HLA-DQA1*05 correlates with characteristics of pediatric IBD. Within a multi-center cohort in Poland, the phenotype at diagnosis and worst flare was established and HLA-DQA1*05 status was assessed enabling genotype-phenotype analyses. HLA-DQA1*05 was present in 221 (55.1%) out of 401 children with IBD (UC n = 188, Crohn's disease n = 213). In UC, the presence of HLA-DQA1*05 was moderately associated with a large extent of colonic inflammation at diagnosis (E4 55% more frequent in HLA-DQA1*05-positive patients, p = 0.012). PUCAI at diagnosis (p = 0.078) and the time from UC diagnosis to the first administration of biologic treatment (p = 0.054) did not differ depending on HLA-DQA1*05 status. The number of days of hospitalization for exacerbation was analyzed in 98 patients for whom sufficient follow-up was available and did not differ depending on HLA-DQA1*05 carriership (p = 0.066). HLA-DQA1*05 carriers with CD were less likely to present with both stenosing and penetrating disease (B2B3, p = 0.048) and to have active disease proximal to the ligament of Treitz (L4a) at the worst flare (p = 0.046). Future research focusing on explaining and preventing anti-TNF immunogenicity should take into account that ADA may develop not only as an isolated reaction to anti-TNF exposure but also as a consequence of intrinsic differences in the early course of UC.

Genetic Variants of DMBT1 and SFTPD and Disease Severity in Paediatric Inflammatory Bowel Disease-A Polish Population-Based Study.

Deleted in malignant brain tumours 1 protein (DMBT1) and surfactant protein D (SFTPD) are antimicrobial peptides previously linked to inflammatory bowel disease (IBD) susceptibility. This study attempts to link the most potential IBD-associated polymorphisms in DMBT1 and SFTPD with the disease severity in children. A total of 406 IBD patients (Crohn's disease (CD) n = 214 and ulcerative colitis (UC) n = 192) were genotyped using hydrolysis probe assay. Clinical expression was described by disease activity scales, albumin and C-reactive protein levels, localisation and behaviour (Paris classification), systemic steroid, immunosuppressive, biological, and surgical treatment, number of exacerbation-caused hospitalisations, relapses and nutritional status. IBD patients with the risk genotype (AA) in DMBT1 rs2981804 had more frequent biological treatment (AA: vs. AG/GG; p = 0.012), concomitant diseases (AA vs. AG vs. GG; p = 0.015) and cutaneous manifestations (AA vs. AG/GG, p = 0.008). In UC, rs2981804 genotypes might be linked with albumin concentrations at diagnosis (AA vs. AG vs. GG; p = 0.009). In CD, DMBT1 rs2981745 was significantly associated with the number of severe relapses per year of disease (p = 0.020) and time-to-immunosuppression (p = 0.045). SFTPD was seemingly found to be associated with age at first immunosuppression in IBD (CC vs. CT vs. TT; p = 0.048). In conclusion, selected polymorphisms of DMBT1 and SFTPD might be associated with some disease severity measures in children with IBD. However, the magnitude of associations and their clinical relevance might be minor.

Comparison of Subjective and Objective Methods to Measure the Physical Activity of Non-Depressed Middle-Aged Healthy Subjects with Normal Cognitive Function and Mild Cognitive Impairment-A Cross-Sectional Study.

This study compared subjective and objective methods of measuring different categories of physical activity in non-depressed middle-aged subjects with normal cognitive function (NCF) and mild cognitive impairment (MCI). In total, 75 participants (NCF: n = 48, MCI: n = 27) were recruited and physical activity was assessed for seven days using the ActiGraph and the International Physical Activity Questionnaire (IPAQ). Anthropometric parameters, body compositions, resting metabolic rate, and energy expenditure were also assessed. ActiGraph data indicated that subjects with NCF were more active than MCI subjects. A comparison of the IPAQ and the ActiGraph data revealed a significant correlation between these methods for total (r = 0.3315, p < 0.01) and moderate (r = 0.3896, p < 0.01) physical activity in the total population and moderate activity (r = 0.2893, p < 0.05) within the NCF group. No associations between these methods were found within the MCI group. Independent predictors of subjectively evaluated total physical activity were alcohol consumption (p = 0.0358) and socio-professional status (p = 0.0288), while weight (p = 0.0285) and the Montreal Cognitive Assessment results (p = 0.0309) were independent predictors of objectively measured physical activity. In conclusion, the long version of IPAQ is a more reliable tool to assess PA in subjects with NCF than those with MCI. More studies are needed to confirm this finding.

Apolipoprotein E variants correlate with the clinical presentation of paediatric inflammatory bowel disease: A cross-sectional study.

BACKGROUND: It has been suggested that apolipoprotein E (APOE) polymorphisms are associated with the risk of developing inflammatory bowel disease (IBD) and the early age of disease onset. However, there are no reports regarding the relationship with clinical characteristics and disease severity. AIM: To summarise that APOE polymorphisms are associated with the risk of developing IBD and the early age of disease onset. METHODS: In total, 406 patients aged 3-18 with IBD (192 had ulcerative colitis and 214 had Crohn's disease) were genotyped using the TaqMan hydrolysis probe assay. Clinical expression was described at diagnosis and the worst flare by disease activity scales, albumin and C-reactive protein levels, localisation and behaviour (Paris classification). Systemic steroid intake with the total number of courses, immunosuppressive, biological, and surgical treatment with the time and age of the first intervention were determined. The total number of exacerbation-caused hospitalisations, the number of days spent in hospital due to exacerbation, the number of relapses, and severe relapses were also estimated. RESULTS: Ulcerative colitis patients with the APOEε4 allele had lower C-reactive protein values at diagnosis (P = 0.0435) and the worst flare (P = 0.0013) compared to patients with the APOEε2 allele and genotype APOEε3/ε3. Crohn's disease patients with the APOEε2 allele scored lower on the Pediatric Crohn's Disease Activity Index at diagnosis (P = 0.0204). IBD patients with APOEε2 allele spent fewer days in the hospital due to relapse (P = 0.0440). CONCLUSION: APOE polymorphisms are associated with the risk of developing IBD and the clinical expression of IBD. However, the clinical relevance of the differences identified is rather modest.

Insolation and Disease Severity in Paediatric Inflammatory Bowel Disease-A Multi-Centre Cross-Sectional Study.

This study was to investigate whether the clinical course of inflammatory bowel disease (IBD) in a Polish paediatric cohort fits a seasonal pattern and depends on insolation. Two hundred and fourteen patients diagnosed with Crohn's disease (CD) and 192 with ulcerative colitis (UC) aged from 3 to 18 years, were recruited in seven centres of similar latitude. The seasons were defined as winter (December-February), spring (March-May), summer (June-August), autumn (September-November). The year was also divided depending on insolation threshold (3.0 kWh/m2/day). Patients diagnosed with IBD when the isolation was >3 kWh/m2/day had poorer nutritional status than those diagnosed while insolation was below threshold (lower standardised BMI at diagnosis (-0.81 ([-1.34]-[-0.03]) vs. -0.52 ([-1.15]-0.15); p = 0.0320) and worst flare (-0.93 ([-1.37]-[-0.05]) vs. -0.66 ([-1.23]-0.17); p = 0.0344), with the need for more frequent biological treatment (45.5% vs. 32.7%, p = 0.0100). Patients diagnosed in winter were significantly younger at diagnosis (11.4 vs. 13.0; padj = 0.0180) and first immunosuppressive treatment (11.3 vs. 13.3; padj = 0.0109) than those diagnosed in other seasons. CD patients diagnosed in months with higher insolation spent more days in hospital than those diagnosed in months with lower insolation [4.6 (1.8-11.8) vs. 2.9 (1.3-6.2); p = 0.0482]. CD patients diagnosed in summer had significantly more concomitant diseases. In patients with CD, the occurrence of the worst flare was more frequent in autumn. Furthermore, the season of birth was associated with Pediatric Crohn's Disease Activity Index at worst flare and earlier surgery. In conclusion, several clinical parameters are associated with insolation, the season of diagnosis and season of birth in the clinical course of Crohn's disease.

The effectiveness of Lactobacillus reuteri DSM 17938 as an adjunct to macrogol in the treatment of functional constipation in children. A randomized, double-blind, placebo-controlled, multicentre trial.

OBJECTIVE: Constipation is one of the most common problems among children, with a prevalence ranging from 7 to 30%. It is treated with defecation training and laxative medications. However, many patients do not respond to the standard therapy. There is, therefore, an increasing interest in probiotics for the treatment of functional constipation. STUDY DESIGN: The aim of this study was to assess the effectiveness of Lactobacillus reuteri DSM 17938 as an adjunct to macrogol in the treatment of functional, intractable constipation in children. A double-blind, placebo-controlled, randomized, multicentre trial involved a group of 129 children with functional constipation who were treated with a poor effect for at least two months prior to the study. Patients were randomly assigned to one of the two groups: 1. L. reuteri DSM 17938 and macrogol or 2. macrogol and matching placebo for 8 weeks. RESULTS: 121 patients completed the study. Almost all patients (119/129) increased their bowel movements in both groups (59 vs 60, ns.) and there was no statistically significant difference in the number of bowel movements per week in week 8 between the study and the placebo group (7.5±3.3 vs 6.9±2.5, respectively). Additionally, there were no significant differences between groups in the numbers of patients complaining of pain during defecation (13/47 vs 8/53), abdominal pain (19/41 vs 25/36), withholding stools (15/45 vs 13/48), passing hard stools (7/53 vs 3/58) or large stools (14/46 vs 12/49), and faecal incontinence (17/43 vs 11/50). CONCLUSION: L. reuteri DSM 17938 supplementation as an additional therapy to macrogol did not have any beneficial effect on the treatment of functional constipation in children aged 3-7 years.

13C Methacetin Breath Test for Assessment of Microsomal Liver Function: Methodology and Clinical Application.

Assessment of the liver function, and the need of constant monitoring of the organ's capacity, concerns not only patients with primary liver diseases, but also those at risk of hepatopathies secondary to other chronic diseases. Most commonly, the diagnostics is based on measurements of static biochemical parameters, which allow us to draw conclusions only indirectly about the function and the degree of damage of the organ. On the other hand, liver biopsy is an invasive procedure and therefore it is associated with a considerable risk of complications. Dynamic tests enable us to assess quantitatively the organ's functional reserve by analyzing the kinetics of the metabolization of the substrate by the liver. In practice applied are breath tests using substances such as aminopyrine, caffeine, methacetin, erythromycin (for assessment of the microsomal function); phenylalanine, galactose (for assessment of the cytosolic function); methionine, octanoate, ketoisocaproic acid (for assessment of the mitochondrial function). The test with 13C methacetin belongs to the best described and most widely applied methods in noninvasive liver function assessment. Due to the rising availability of this method, knowledge concerning its limitations and controversies regarding the methodology, as well as its usefulness in chosen groups of patients, seems to be vital.