Eleftheria Roma-Giannikou

Prospective multicentre study on antibiotic resistance of Helicobacter pylori strains obtained from children living in Europe

Aim: To prospectively assess the antibacterial resistance rate in Helicobacter pylori strains obtained from symptomatic children in Europe. Methods: During a 4-year period, 17 paediatric centres from 14 European countries reported prospectively on patients infected with H pylori, for whom antibiotic susceptibility was tested. Results: A total of 1233 patients were reported from Northern (3%), Western (70%), Eastern (9%) and Southern Europe (18%); 41% originated from outside Europe as indicated by mother’s birth-country; 13% were <6 years of age, 43% 6–11 years of age and 44% >11 years of age. Testing was carried out before the first treatment (group A, n = 1037), and after treatment failure (group B, n = 196). Overall resistance to clarithromycin was detected in 24% (mean, A: 20%, B: 42%). The primary clarithromycin resistance rate was higher in boys (odds ratio (OR) 1.58; 1.12 to 2.24, p = 0.01), in children <6 years compared with >12 years (OR 1.82, 1.10 to 3.03, p = 0.020) and in patients living in Southern Europe compared with those living in Northern Europe (OR 2.25; 1.52 to 3.30, p<0.001). Overall resistance rate to metronidazole was 25% (A: 23%, B: 35%) and higher in children born outside Europe (A: adjusted. OR 2.42, 95% CI: 1.61 to 3.66, p<0.001). Resistance to both antibiotics occurred in 6.9% (A: 5.3%, B: 15.3%). Resistance to amoxicillin was exceptional (0.6%). Children with peptic ulcer disease (80/1180, 6.8%) were older than patients without ulcer (p = 0.001). Conclusion: The primary resistance rate of H pylori strains obtained from unselected children in Europe is high. The use of antibiotics for other indications seems to be the major risk factor for development of primary resistance.

Neck circumference: a useful screening tool of cardiovascular risk in children

Early identification of cardiovascular risk factors consists an essential target for public health. The current study aims to examine the association between neck circumference and several cardiovascular risk factors and to compare it with well‐established anthropometric indices.

Frequency and risk factors of gastric and duodenal ulcers or erosions in children: a prospective 1-month European multicenter study

There are no solid figures of the frequency of ulcer disease during childhood in Europe. We assessed its frequency and analyzed known risk factors. Patients and methods Ulcers, erosions, indications, and risk factors were recorded in all children undergoing an upper gastrointestinal endoscopy in a prospective study carried out during 1-month simultaneously in 19 centers among 14 European countries. Results Ulcers and/or erosions were observed in 56 out of 694 children. Children with ulcers/erosions were significantly older than those without lesions (10.3±5.5 vs. 8.1±5.7 years, P=0.002). Helicobacter pylori infection was present in 15 of 56 children (27%) where NSAIDs were used in eight, steroids in five, immune-suppressive drugs in five, antibiotics in six, antacids in one, H2-blockers in six and proton pump inhibitors in eight children (more than one risk factor was detected in 32 of 56 children). No risk factors were observed in 24 of 56 children (43%). The main indications for endoscopy were epigastric or abdominal pain (24%) and suspicion of gastroesophageal reflux disease (15%). Similarly, epigastric tenderness, hematemesis, melena, and weight stagnation were significantly associated with ulcers/erosions, whereas sex, H. pylori infection, socioeconomic and lifestyle factors were equally distributed. Conclusion Although limited by the short-time duration and the heterogeneity of the patients included throughout the 19 centers, our study shows a frequency of 8.1% of ulcers and/or erosions in children, occurring mainly in the second decade of life. H. pylori infection and gastrotoxic medications were less frequently implicated than expected.

CagA and VacA Polymorphisms Do Not Correlate with Severity of Histopathological Lesions in Helicobacter pylori-Infected Greek Children

ABSTRACT The presence of various numbers of EPIYA tyrosine phosphorylation motifs in the CagA protein of Helicobacter pylori has been suggested to contribute to pathogenesis in adults. In this prospective study, we characterized H. pylori isolates from symptomatic children, with reference to the diversity of functional EPIYA motifs in the CagA protein and vacA isotypes, and assessed the potential correlation with the histopathological manifestations of the infection. We analyzed 105 H. pylori isolates from 98 children and determined the diversity of EPIYA motifs in CagA by amplification and sequencing of the 3′ variable region of the cagA gene as well as vacA isotypes for the signal, middle, and intermediate regions. CagA phosphorylation and levels of secreted IL-8 were determined following in vitro infection of AGS gastric epithelial cells. Histopathological evaluation of H. pylori colonization, activity, and severity of the associated gastritis was performed according to the updated Sydney criteria. EPIYA A (GLKN[ST]EPIYAKVNKKK), EPIYA B (Q[V/A]ASPEPIY[A/T]QVAKKVNAKI), and EPIYA C (RS[V/A]SPEPIYATIDDLG) motifs were detected in the ABC (46.6%) and ABCC (17.1%) combinations. No isolates harboring more than two EPIYA C motifs in CagA were found. The presence of isogenic strains with variable numbers of CagA EPIYA C motifs within the same patient was detected in seven cases. Occurrence of increasing numbers of EPIYA C motifs correlated strongly with presence of a high-vacuolation (s1 or s2/i1/m1) phenotype and age. A weak positive correlation was observed between vacuolating vacA genotypes and presence of nodular gastritis. However, CagA- and VacA-dependent pathogenicities were not found to contribute to severity of histopathology manifestations in H. pylori-infected children.

Malignancy and mortality in pediatric patients with inflammatory bowel disease: a multinational study from the porto pediatric IBD group.

Background:The combination of the severity of pediatric-onset inflammatory bowel disease (IBD) phenotypes and the need for intense medical treatment may increase the risk of malignancy and mortality, but evidence regarding the extent of the problem is scarce. Therefore, the Porto Pediatric IBD working group of ESPGHAN conducted a multinational-based survey of cancer and mortality in pediatric IBD. Methods:A survey among pediatric gastroenterologists of 20 European countries and Israel on cancer and/or mortality in the pediatric patient population with IBD was undertaken. One representative from each country repeatedly contacted all pediatric gastroenterologists from each country for reporting retrospectively cancer and/or mortality of pediatric patients with IBD after IBD onset, during 2006–2011. Results:We identified 18 cases of cancers and/or 31 deaths in 44 children (26 males) who were diagnosed with IBD (ulcerative colitis, n = 21) at a median age of 10.0 years (inter quartile range, 3.0–14.0). Causes of mortality were infectious (n = 14), cancer (n = 5), uncontrolled disease activity of IBD (n = 4), procedure-related (n = 3), other non-IBD related diseases (n = 3), and unknown (n = 2). The most common malignancies were hematopoietic tumors (n = 11), of which 3 were hepatosplenic T-cell lymphoma and 3 Ebstein–Barr virus–associated lymphomas. Conclusions:Cancer and mortality in pediatric IBD are rare, but cumulative rates are not insignificant. Mortality is primarily related to infections, particularly in patients with 2 or more immunosuppressive agents, followed by cancer and uncontrolled disease. At least 6 lymphomas were likely treatment-associated by virtue of their phenotype.

The impact of oral glutamine supplementation on the intestinal permeability and incidence of necrotizing enterocolitis/septicemia in premature neonates

Objective. To examine the impact of oral glutamine (Gln) supplementation on gut integrity and on the incidence of necrotizing enterocolitis (NEC)/septicemia of premature neonates. Methods. Preterm neonates (n = 101, gestational age <34 weeks, birth weight <2000 g) were randomly allocated to receive from day 3 to day 30 postpartum, either oral Gln (0.3 g/kg/day, n = 51-Gln group) or placebo (caloreen-isocaloric, n = 50-control group). Intestinal permeability was determined from the urinary lactulose/mannitol recovery (L/M ratio) following their oral administration and assessed at three time points: day 2 (before first administration), day 7 and day 30 of life. The incidence of NEC and septicemia over the study period was also recorded. Results. A decrease of lactulose recovery at days 7 (p = 0.001) and 30 (p < 0.001) and a decrease of L/M ratio at day 7 (p = 0.002) were observed only in the Gln group. Lactulose recovery and L/M ratio at day 7 (p = 0.022 and p = 0.004, respectively), as well as lactulose recovery (p = 0.001), mannitol recovery (p = 0.042), and L/M ratio (p = 0.001) at day 30, were decreased in the Gln group as compared to controls. NEC and septicemia were lower in the Gln group at the end of the first week (p = 0.009 and p = 0.041, respectively) and up to the end of the study (p < 0.001 and p = 0.048, respectively). Conclusion. Oral Gln administration may have beneficial effects on intestinal integrity and the overall incidence of NEC/septicemia in preterm infants.

New effective treatment regimen for children infected with a double-resistant Helicobacter pylori strain.

Background: The increasing number of pediatric patients infected with multiresistant Helicobacter pylori strains calls for evaluation of treatment regimens. Second-line antibiotics such as tetracycline or quinolones are not licensed for children. Because in vivo resistance to metronidazole may be overcome in vivo by a high dose and prolonged intake, we evaluated the eradication rate and side effects of a high-dose triple therapy in pediatric patients with culture-proven double resistance. Patients and Methods: In this open multicentre trial, 62 children (<18 years, body weight >15 kg) infected with an H pylori strain resistant to metronidazole and clarithromycin were treated according to body weight classes with amoxicillin (∼75 mg/kg/day), metronidazole (∼25 mg/kg/day) and esomeprazole (∼1.5 mg/kg/day) for 2 weeks. Adherence and adverse events were assessed by a 2-week diary and telephone interviews at days 7 and 14 of treatment. Primary outcome was a negative 13C-urea breath test after 6 weeks. Results: Of 62 patients, 5 were lost to follow-up, 12 were nonadherent, and 45 treated per protocol. Eradication rates were 66% (41/62) [confidence interval 54–78] (intention to treat) and 73% (33/45) [confidence interval 60–86] (per protocol). Success of treatment was not related to dose per kilogram body weight. Mild to moderate adverse events were reported by 21 patients, including nausea (10.8%), diarrhoea (8.9%), vomiting (7.1%), abdominal pain (5.4%), and headache (3.6%), and led to discontinuation in 1 child. Conclusion: High-dose amoxicillin, metronidazole, and esomeprazole for 2 weeks is a good treatment option in children infected with a double resistant H pylori strain.

Endoscopic tests for the diagnosis of Helicobacter pylori infection in children: Validation of rapid urease test.

Background:  Rapid urease test (CLO‐test) is an inexpensive and quick method for diagnosis of Helicobacter pylori infection with controversial results in children. We evaluated the performance of CLO‐test in relation to endoscopic and histological findings in children with H. pylori infection.

Dental Caries and Periodontal Disease in Children and Adolescents with Inflammatory Bowel Disease: A Case-Control Study.

Background:Previous reports have demonstrated a higher prevalence of dental caries and periodontal disease in adults with inflammatory bowel disease (IBD), but similar data in children and adolescents do not exist. The aim of the study was to evaluate the status of dental caries, oral hygiene, gingival status and periodontal treatment needs of children with IBD. Methods:In this case–control study, 55 children on remission from a single outpatient IBD clinic, aged 4 to 18 years (12.27 ± 3.67 yr) and 55 matched systemically healthy controls of a dental practice were assessed prospectively. The evaluation included medical history, dental questionnaire in both groups, and previous and current medical therapy of children with IBD. Additionally, the decayed, missing, and filled tooth (dmf-t or DMF-T), simplified gingival, plaque control record and community periodontal treatment needs indices were evaluated. Results:Children with IBD compared with controls had a statistically significant (P < 0.001) higher dmf-t (2.95 versus 0.91) or DMF-T (5.81 versus 2.04) index and a higher gingival inflammation (simplified gingival, 40% versus 24%) although the respectively dental plaque index showed no significant difference (plaque control record, 42% versus 41%). Also, the community periodontal treatment needs was significantly higher compared with controls (P < 0.001); most of the patients with IBD needed treatment of gingivitis (47% versus 4%), and none of them had healthy periodontium (0% versus 69%). Conclusions:The results of this case–control study demonstrate a higher frequency of dental caries, more clinical signs of gingival inflammation, and increased periodontal treatment needs in children and adolescents with IBD despite similar oral hygiene status.

Histological deterioration of obesity-related glomerulopathy despite the loss of proteinuria with weight reduction.

Sirs, We describe a 13-year-old girl with obesity-related glomerulopathy (ORG) who presented to our department with a 2-year history of proteinuria (>500 mg/24 h) and microalbuminuria at a rate of 544 mg/dl (normal <20 mg/dl). Her obesity dated from the age of 7 years. Physical examination revealed an obese girl with a body weight (BW) of 130 kg, height of 183 cm, body mass index (BMI) 38.9 kg/m, and blood pressure (BP) of 150/60 mmHg. The results of laboratory investigations, including chemistry, hematology, and immunology tests, were normal. The estimated glomerular filtration rate (eGFR) was 144 ml/min/1.73 m, and her urine contained 70 mg/dl of protein without hematuria. The glucose tolerance test revealed insulin resistance with a fasting glucose insulin ratio (FGIR) of 3.86 (normal values >7). Renal ultrasonography revealed her kidneys to be unequal in size, with the right kidney shorter than the left one (11.84 vs. 13.68 cm, respectively; normal 10.3 cm). Based on these ultrasonographic findings, both kidneys were larger than normal for age–weight controlled children [1]. Taken together, our findings raised the possibility of a metabolic syndrome-related kidney disease. A renal biopsy was therefore performed. Of the 30 glomeruli tested in the biopsied tissue, the majority were hypertrophied, one was hyalinized, and one was sclerosed. Evidence of segmental mesangial expansion was also detected. Focal fibrotic lesions were present in <5% of the cortical interstitium. These findings were compatible with the diagnosis of ORG (Fig. 1a). The recommended treatment consisted of weight reduction, changes in lifestyle conditions, and single-drug therapy consisting of an angiotensin-converting enzyme (ACE) inhibitor (enalapril 20 mg as a single daily dose). On re-evaluation 1 year later, her BW was 91 kg (loss of 39 kg, 30% reduction). She was normotensive with no proteinuria, and her eGFR was 127 ml/min/1.73 m. At her 2-year follow-up, mild proteinuria had reappeared (0.7 g in a 24h urine collection) and her eGFR was 112 ml/min/ 1.73 m—even though she had continued to lose weight (50 kg less than her weight at initial presentation, equaling a total BW reduction of 38.5%). Her BP was normal (110/ 70 mmHg). We performed a repeat renal biopsy at this time. Three of 14 glomeruli per section were found to be totally sclerosed, and one showed focal segmental sclerosis. Expansion of the mesangial matrix affected most of the glomeruli. Tubulointerstitial fibrosis affecting about 5% of the cortical area was again detected, as in the first biopsy (Fig. 1b). The diagnosis of focal segmental glomeruloscerosis (FSGS) secondary to obesity-related glomerulopathy was made, and she was advised to continue both the pharmaceutical treatment and her efforts to stabilize her weight. H. Georgaki-Angelaki (*) :N. Stergiou Department of Paediatric Nephrology, “Aghia Sophia” Children’s Hospital, Thivon and Levadias Street, Athens 11527, Greece e-mail: pednephr@paidon-agiasofia.gr