Josef Sýkora

Epidemiology of Helicobacter pylori infection in asymptomatic children: a prospective population-based study from the Czech Republic. Application of a monoclonal-based antigen-in-stool enzyme immunoassay.

Background:  Acquisition of Helicobacter pylori occurs mainly in childhood and is significantly influenced by geographical variations. The aim of this study is to evaluate the prevalence of H. pylori infection in a population‐based sample of asymptomatic children in the Czech Republic. Furthermore, this study aims to identify potential risk factors associated with this infection.

Evaluation of faecal calprotectin as a valuable non-invasive marker in distinguishing gut pathogens in young children with acute gastroenteritis

Aim:  The aim of the study is to evaluate faecal calprotectin (f‐CP) in children ≤3 years of age with acute gastroenteritis (AG) as an early predictor of bacterial inflammation.

Gastric emptying of solids in children with H. pylori-positive and H. pylori-negative non-ulcer dyspepsia.

Objective: There is currently no data available in children on possible relationships among Helicobacter pylori, gastric motility and gastric inflammation. This is a prospective study of gastric emptying (GE) in symptomatic children with and without H. pylori who met symptom-based criteria for non-ulcer dyspepsia (NUD). Methods: 47 consecutive dyspeptic patients (23 males; age range, 7 to 18 years) were enrolled. All patients had extensive negative diagnostic investigations. Scintigraphic solid-phase gastric emptying was assessed. Results: 21 H. pylori-positive and 26 H. pylori-negative patients were identified with non-ulcer dyspepsia. The groups were not different in clinical symptoms except that pain related to feeding was more frequent in infected children (P < 0.03). Nodular antral gastritis was found more frequently in the H. pylori positive group (P < 0.0001). The gastritis score was more severe in H. pylori infected than H. pylori negative patients in both fundic and body mucosa (P < 0.001). Within the H. pylori-positive NUD group, the mean half-time GE of a solid meal was significantly accelerated compared to the non-infected group (P < 0.05). There was no difference in the intragastric food distribution and curves of gastric emptying of both groups. A significant relationship was found between the degree of gastric body inflammation gastric emptying, but not antral inflammation. Gastric emptying rate did not differ by sex or age of the subjects in either group. Conclusions: In dyspeptic children with H. pylori, gastric emptying of a solid was significantly accelerated compared with symptomatic H. pylori uninfected patients. This suggests that H. pylori is able to induce gastric emptying acceleration. Our findings add more information on H. pylori infection and gastroduodenal disease.

Helicobacter pylori in Pediatrics: H. pylori in Children

This article reviewed the important publications on Helicobacter pylori research with children between April 2010 and March 2011. The most interesting studies in the last year lend further weight to the evidence for vertical transmission of H. pylori. The discovery of a potential role for jhp0562, the gene which encodes for the cell envelope protein glycosyltransferase, in the progression to peptic ulcer disease is also very interesting as it may provide a novel way to distinguish children at risk of peptic ulcer disease from those who are not, and so determine those who requires treatment to eradicate H. pylori. The rise in non‐H. pylori‐associated ulcers and erosions continues to be reported with no apparent risk factors for these ulcers identified to date. High levels of treatment failure continue to be reported, and there remains an urgent need for more effective treatment regimes for children.

Paediatric Rome III Criteria-Related Abdominal Pain Is Associated With Helicobacter pylori and Not With Calprotectin.

Objectives: Abdominal pain–related functional gastrointestinal disorders in children include functional dyspepsia, functional abdominal pain, irritable bowel syndrome, and abdominal migraine. We aimed to evaluate a possible association between functional abdominal pain disorders and Helicobacter pylori infection and faecal calprotectin level. Methods: Prospective observational study including consecutive children with functional gastrointestinal disorders fulfilling Rome III criteria (cases) and age/sex-matched healthy controls. H pylori has been detected by biopsy-based tests and stool-antigen detection, faecal calprotectin by enzyme-linked immunosorbent assay. Results: A total of 56 cases (27 with functional dyspepsia) and 56 controls were enrolled. H pylori being detected in 17 of 56 cases (30.4%) and 4 of 56 controls (7.1%, odds ratio: 5.7; 95% confidence interval [CI]: 1.8–18.2, P = 0.003). H pylori was detected significantly more frequently in cases with functional dyspepsia (14/27, 51.9% odds ratio: 14.0; 95% CI: 3.9–49.7, P = 0.00001) than in controls and not in cases with other well-recognized functional gastrointestinal complaints (3/29, 10.3%). The median faecal calprotectin level was similar in cases (7.8 &mgr;g/g, 95% CI: 7.8–8.4) including those with gastritis, and controls (9.1 &mgr;g/g, 95% CI: 7.8–11.3). Gastritis features were more frequent in H pylori–infected and noninfected cases with functional dyspepsia (27/27, 100%) than in cases with other abdominal functional complaints (15/29, 51.7%, P = 0.007). Conclusions: H pylori gastritis and noninfectious gastritis were associated with functional dyspepsia in children referred for abdominal pain–related functional gastrointestinal disorders while faecal calprotectin is not a predictor of gastritis and is similar in children with functional abdominal pain symptoms and in controls.

First case report of rare congenital adrenal insufficiency caused by mutations in the CYP11A1 gene in the Czech Republic.

Abstract We characterized a case of congenital adrenal insufficiency caused by cholesterol side-chain cleavage enzyme (P450scc) deficiency. The patient presented after birth with cardiopulmonary instability, hyponatremia, hyperkalemia, hypoglycemia and metabolic acidosis. We confirmed primary adrenal insufficiency. There were no signs of the external genitalia virilism. The replacement therapy with glucocorticoids and mineralocorticoids led to normal laboratory results. At the age of 12 years, we confirmed hypergonadotropic hypogonadism, which revealed disorder of steroidogenesis in the adrenal glands and in the gonads. The enzymatic block was found at the beginning of steroidogenesis. The mutation was confirmed in the CYP11A1 gene. The patient is compound heterozygote for the novel CYP11A1 missense mutation c.412G>A (p.Gly138Arg) in exon 2 and frameshift mutation c.508_509delCT (p.Leu170Valfs*30) in exon 3. The CYP11A1: c.412G>A (p.Gly138Arg) was predicted as pathogenic by in silico analysis. So far, only 19 patients with CYP11A1 mutations causing P450scc deficiency have been reported worldwide. There are no related reports in the Czech Republic.

Inflammatory bowel disease incidence in Czech children: A regional prospective study, 2000-2015

AIM To examine the incidence and trends in pediatric inflammatory bowel diseases (IBDs) over 2000-2015 and project the incidence to 2018. METHODS A 16-year prospective study of IBD patients < 19 years of age was conducted in the Czech Republic (the Pilsen region). All incident IBD cases within a well-defined geographical area were retrieved from a prospectively collected computerized clinical database. Historical Czech data were used for comparison (1990-2001). Our catchment population was determined from the census data. We calculated the incidence by relating the number of newly diagnosed cases to the size of the pediatric population-at-risk in each calendar year. Age/sex, disease type, place of residence, and race/ethnicity were identified. RESULTS In total, 170 new IBD cases [105 Crohn’s disease (CD), 48 ulcerative colitis (UC), and 17 IBD-unclassified (IBD-U)] were identified. The median age at IBD diagnosis was 14.2 years, 59.4% were males, and 97.1% were Caucasians. A male preponderance of IBD (P = 0.026) and CD (P = 0.016) was observed. With 109209 person-years in the catchment area, the average incidence of IBD per 100000 person-years was 10.0 (6.2 for CD, 2.8 for UC, and 1.0 for IBD-U) for children aged 0 to 19 years; for those aged 0 to 15 years, the incidence rate was 7.3 (4.6 for CD, 2.0 for UC, and 0.7 for IBD-U). An increase in incidence with age was observed (P = 0.0003). Over the 16-year period, the incidence increased for IBD patients (P = 0.01) and CD in particular (P < 0.0001), whereas the incidence for UC (P = 0.09) and IBD-U (P = 0.339) remained unchanged. IBD-projected data from 2016 to 2018 were 12.1, 12.3 and 12.6 per 100000 person-years, respectively. CONCLUSION Pediatric-onset IBD incidence is around its highest point. The increase, which is particularly pronounced for CD, may be challenging to relate to causes of pediatric disease.

Fistulizing Anorectal Crohn Disease in a Child With Severe HLA-B27-associated Enthesitis-related Arthritis

Juvenile idiopathic arthritis (JIA) represents a family of childhood arthropathies characterized by chronic synovial inflammation. Enthesitis-related arthritis (ERA), a subgroup of JIA and formerly known as juvenile ankylosing spondylitis, is frequently associated with inflammatory bowel disease (IBD). ERA represents the pediatric form of spondyloarthropathy (SA) in adults. The typical presentations of ERA are seronegative oligoarthritis associated with enthesitis affecting the joints of the lower extremities. Abnormalities of the axial skeleton, including sacroiliitis, are absent in the early stages of the disease (1). The histocompatibility antigen HLA-B27 is strongly linked with adult ankylosing spondylitis (AS) (90%) and with the risk for the development of AS in IBD (2). This antigen is associated with 25% of cases of IBD and is present in 70% of patients with IBD having inflammation of the axial skeleton (3). The prevalence of the HLA-B27 antigen in adult patients with Crohn disease (CD) has been found to be 12%, although it is 78% in patients with CD and AS (4). The prevalence of IBD is increased in adults with other autoimmune diseases, particularly AS, and in those with reactive and psoriatic arthritis (5). Indeed, in 1 study, ileocolonoscopies confirmed gut inflammation in 57% of adults with SA (6). Another study also reported the eventual development of CD in patients with SA (7). Conversely, arthritic manifestations are common extraintestinal symptoms of CD in children (8). In another study, 35% of patients with CD fulfilled criteria consistent with the European Spondyloarthropathy Study Group for SA (1). To our best knowledge, this is the

Current global trends in the incidence of pediatric-onset inflammatory bowel disease

AIM To perform a comprehensive review and provide an up-to-date synopsis of the incidence and trends of inflammatory bowel disease (IBD). METHODS We systematically searched the MEDLINE (source PubMed), EMBASE and Cochrane Library databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (period: 1985-2018) to identify studies reporting population-based data on the incidence of pediatric-onset (< 19 years at diagnosis) IBD in full manuscripts. Two authors carried out screening and data extraction. Choropleth interactive maps and temporal trends were used to illustrate the international differences and incidences of and changes in IBD and subtypes. RESULTS In total, one hundred forty studies reporting data from 38 countries were considered in this review. The highest annual pediatric incidences of IBD were 23/100000 person-years in Europe, 15.2/100000 in North America, and 11.4/100000 in Asia/the Middle East and Oceania. The highest annual incidences of Crohn’s disease (CD) were 13.9/100000 in North America and 12.3/100000 in Europe. The highest annual incidences of ulcerative colitis (UC) were 15.0/100000 in Europe and 10.6/100000 in North America. The highest annual incidences of IBD-unclassified (IBD-U) were 3.6/100000 in Europe and 2.1/100000 in North America. In the time-trend analyses, 67% of CD, 46% of UC and 11% of IBD-U studies reported an increasing incidence (P < 0.05). The risk of IBD is increasing among first-generation of migrant populations. CONCLUSION Globally, the incidence of IBD varies greatly by geographical areas. The steadily increasing incidence of pediatric IBD over time indicates its emergence as a global disease, suggesting that studies should investigate the environmental risk factors among pediatric cohorts.

First 2 cases with thiamine-responsive megaloblastic anemia in the Czech Republic, a rare form of monogenic diabetes mellitus: a novel mutation in the thiamine transporter SLC19A2 gene-intron 1 mutation c.204+2T>G.

Thiamine‐responsive megaloblastic anemia (TRMA) is a rare autosomal recessive disorder caused by mutations in the SLC19A2 gene. To date at least 43 mutations have been reported for the gene encoding a plasma membrane thiamine transporter protein (THTR‐1). TRMA has been reported in less than 80 cases worldwide. Here, we illustrate 2 female patients with TRMA first diagnosed in the Czech Republic and in central Europe being confirmed by sequencing of the THTR‐1 gene SLC19A2. Both subjects are compound heterozygotes with 3 different mutations in the SLC19A2 gene. In case 2, the SLC19A2 intron 1 mutation c.204+2T>G has never been reported before. TRMA subjects are at risk of diabetic ketoacidosis during intercurrent disease and arrythmias. Thiamine supplementation has prevented hematological disorders over a few years in both pediatric subjects, and improved glycaemic control of diabetes mellitus. Patient 1 was suffering from hearing loss and rod‐cone dystrophy at the time of diagnosis, however, she was unresponsive to thiamine substitution. Our patient 2 developed the hearing loss despite the early thiamine substitution, however no visual disorder had developed. The novel mutation described here extends the list of SLC19A2 mutations causing TRMA.