Publications by authors named "Nicolas Kalach"

70 Publications

Systematic Review and Meta-Analysis of Histological Gastric Biopsies Aspects According to the Updated Sydney System in Children.

J Pediatr Gastroenterol Nutr 2021 Jul 28. Epub 2021 Jul 28.

Pediatric Clinic, Saint Vincent de Paul Hospital, Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Catholic University of Lille, France Department of Pediatrics, Referral Center for Pediatric Gastroenterology and Nutrition, Children's Hospital Zagreb, Zagreb, Croatia Department of Gastroenterology, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, Belgium Kaplan Medical Center, Pediatric Gastroenterology Unit, Rehovot, Israel. University Children's Hospital Ljubljana, Department of Gastroenterology, Hepatology and Nutrition, Faculty of Medicine, Ljubljana, Slovenia. Hospital of Dona Estefania, CHLC, Pediatric Gastroenterology Unit, Lisbon, Portugal. Karolinska University Hospital, Department of Pediatrics, Stockholm, Sweden. Queen Mary's Hospital for children Epsom & St Helier NHS Trust Carshalton, Surrey, United Kingdom. Hospital Universitario Puerta de Hierro-Majadahonda, Pediatric Gastroenterology Unit, Madrid, Spain. Bambino Gesù Children's Hospital, Digestive Endoscopy and Surgery Unit, Rome, Italy. INSERM U1053, University of Bordeaux, & National Reference Centre for Campylobacter and Helicobacter, Hopital Pellegrin, Bordeaux, France. Division of Gastroenterology & Hepatology, First Department of Pediatrics, University of Athens, Agia Sofia Children's Hospital, Athens, Greece. Department of Child Health & Nutrition, Istanbul Kent University, Istanbul, Turkey. Microbiology Department, Cochin Hospital, Assistances Publiques des Hôpitaux de Paris (AP-HP), University René Descartes Paris V, Paris, France. Mitera Children's Hospital Athens, Greece. Unidade de Gastrenterologia Pediátrica do Centro Materno Infantil do Norte, Centro Hospitalar Universitário do Porto, Porto, Portugal. Yeditepe University Medical Faculty Department of Pediatrics, Gastroenterology, Hepatology and Nutrition, Ataşehir, Istanbul, Turkey. Vilnius University Clinic of Children's Diseases, Vilnius, Lithuania. Hospital Universitario Doce de Octubre, Servicio de Pediatria, Madrid, Spain. Pathology Department, Saint Vincent de Paul Hospital, Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Catholic University of Lille, France Department of Medical Research, Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Lille Catholic Hospital, Lille, France.

Objectives: A descriptive and comparative study of gastric histological aspects according to the updated Sydney classification (USC), obtained from Helicobacter pylori (H. pylori) positive vs negative children referred for upper gastrointestinal endoscopy.

Methods: The Prisma method was used to perform a systematic review and meta-analysis. Selection criteria were based on following Keywords USC, H. pylori, children, endoscopy, or biopsy. Publication biases were assessed according to the Newcastle-Ottawa Scale and a meta-regression analysis was done. The study was registered on the PROSPERO platform.

Results: Between 1994 and 2017, 1,238 references were found; 97 studies were retained for the systematic review with a total number of 25,867 children; 75 studies were selected for the meta-analysis concerning 5,990 H. pylori infected and 17,782 uninfected children.H. pylori positive vs negative children, according to the USC, showed significantly higher relative risk for gastric antral and corpus chronic inflammation, presence of neutrophils, and of lymphoid follicles, and gastric mucosa atrophy, whereas, intestinal metaplasia showed a significantly higher RR only in antral biopsies.The meta-regression analysis showed that H. pylori positive vs negative children had significantly higher risk only for corpus activity according to age, recurrent abdominal pain, and geographical area of low H. pylori prevalence.

Conclusions: H. pylori infection in children was associated with higher relative risk for gastric antral and corpus chronic inflammation, presence of neutrophils, lymphoid follicles, and rare gastric mucosa atrophy, whereas, rare intestinal metaplasia was only significantly higher in the antral area.
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July 2021

Diagnosis of Infection in a Routine Testing Workflow: Effect of Bacterial Load and Virulence Factors.

J Clin Med 2021 Jun 23;10(13). Epub 2021 Jun 23.

Service de Bactériologie, AP-HP Centre-Université de Paris, Hôpital Cochin, 75014 Paris, France.

Reliable diagnostic methods are mandatory for effective management of infection. Histology and culture are the most common invasive methods in current practice, even if molecular methods are gaining in importance. The performance of these conventional methods varies significantly. We conducted a retrospective study of 1540 adults and 504 children with gastric biopsies taken during endoscopy to assess the impact of bacterial load and the virulence factor on the performance of infection testing. The association between virulence and histology findings was also investigated. With 23S rRNA qPCR confirmed by amplification as the gold standard, culture and histology had lower sensitivity, 74.4% and 73.3%, respectively. However, their sensitivity was enhanced (>90%) in biopsies with high bacterial load (qPCR Ct < 30). Positive status of the strain was associated with high bacterial load (94.9%), thus resulting in more frequent positive culture (94.3%) and histology detection (91.7%) and more severe lesions on histology ( < 0.001). Conversely, the status of the strains was negative in 110/119 (92.4%) of biopsies with low bacterial load (qPCR Ct < 30), 82/90 (91.1%) with negative histology detection and 119/131 (90%) with negative culture findings ( < 0.001). This study highlights the low sensitivity of conventional culture and histology that may lead to false negative diagnosis if used alone. quantification associated with genotyping in routine workflow are essential for a sensitive and reliable diagnosis, to identify patients at high risk and to manage eradication therapies.
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June 2021

Effectiveness of Two Regimens for Colon Cleansing Using Polyethylene Glycol 4000: A Randomized Open Label Trial.

Indian Pediatr 2021 May 28. Epub 2021 May 28.

Hôpital Saint Vincent de Paul, Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université Catholique de Lille, BD de Belfort, 59020 Lille Cedex, France.

Aim: To compare effectiveness, safety and tolerance of two colon cleansing regimens using polyethylene glycol 4000 (PEG) in children.

Methods: Prospective, randomized, open clinical trial carried out in 129 children, 3 to 18 years old undergoing colonoscopy. Patients were randomized into two groups, 64 children received PEG with electrolyte (50 mL/kg) and oral bisacodyl (PEG+B) group or 65 other children received PEG with electrolyte (70 mL/kg) and glycerol enema (PEG+G) group.

Results: Both regimens showed a good colon cleansing effectiveness with the percentage of successful cleansing being 93.8% for PEG+B regimen and 89.1% for PEG+G regimen (P=0.510). There was no statistically significant difference between the pre-regimen and post-regimen laboratory values. The rates of nausea (65.6% vs 31.3%; P<0.001) and bloating (50% vs 17.2%; P<0.001) of PEG+G group were significantly higher than that of PEG+B group.

Conclusion: Both regimens had good efficacy and safety for clon cleansing in children. The tolerance of PEG+B regimen was better.
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May 2021

Systemic steroids have a role in treating esophageal strictures in pediatric eosinophilic esophagitis.

Dig Liver Dis 2021 Mar 15;53(3):324-328. Epub 2020 Dec 15.

Institute of Gastroenterology, Nutrition, and Liver Diseases, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address:

Background: The role of systemic steroids in the treatment of esophageal strictures in children with Eosinophilic Esophagitis (EoE) is poorly defined.

Aims: To describe a cohort of children with EoE-associated esophageal strictures responding to systemic steroids.

Methods: Retrospective review of medical records of children with EoE and moderate (<9 mm) to severe (<6 mm) strictures, who responded clinically and endoscopically to systemic steroids.

Results: Twenty children (median age 10.6 ± 4.2 years; 17 males) from nine centers in six countries were included in the analysis; 16 had moderate and four, severe strictures; 18 had dysphagia or bolus impaction; median diagnostic delay was 8 months (IQR 3.5-35). Eighteen patients received oral systemic steroids (mean dose 1.4 mg/kg/day) for a median of 4 weeks, while two initially received IV steroids. All patients showed clinical improvement and 15/20 became asymptomatic. Stricture resolution at endoscopy was found in 19/20, while histological resolution of EoE (<15 eos/hpf) in 13/20. Only minor side effects were reported: hyperphagia (10/20); weight gain (5/20); hyperactivity (2/20) and acne (1/20). Esophageal dilation was required in 3/20 patients during a median follow-up of 48.5 months (IQR 26.7-73.2).

Conclusion: Children with EoE and esophageal strictures, may benefit from the use of a short course of systemic steroids, avoiding mechanical dilation.
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March 2021

Hydrolyzed Rice Protein-Based Formulas, a Vegetal Alternative in Cow's Milk Allergy.

Nutrients 2020 Aug 31;12(9). Epub 2020 Aug 31.

Department of Paediatrics, Saint Antoine Paediatric Hospital, Saint Vincent de Paul Hospital, Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Catholic University of Lille, 59000 Lille, France.

Formulas adapted to infant feeding, although most of the time made from cow's milk proteins, can be made from hydrolyzed rice protein but they must be classified as "formulas for specific medical needs", according to European regulations. The nutritional quality of rice proteins is thus suitable to be used in infant formulas giving that it is supplemented by certain amino acids which can be lacking. Besides, hydrolysis is required to facilitate their water solubility and digestibility. Owing to a low allergenicity of rice and to the absence of the cross-allergy between milk proteins and rice proteins, these formulas are adapted to the diet of children with cow's milk protein allergy (CMPA), which explains their growing use in some countries. However, CMPA, an expanding disorder, has consequences for growth, bone mineralization, and often has an association with allergy to other foods, including cow's milk extensive hydrolysate, so that a surveillance of the adaption of hydrolyzed rice protein formulas (HRPF) to CMPA, the absence of unexpected side effects, and the appropriate response to its various health hazards seems mandatory. This paper analyses the health problem deriving from CMPA, the industrial development of hydrolyzed rice protein formulas, and the limited number of clinical studies, which confirms, at the moment, a good allergic tolerance and safety. The goal is to better advise heath care professionals on their use of HRPFs during CMPA.
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August 2020

[Helicobacter pylori infection in children].

Rev Prat 2020 Mar;70(3):301-304

Département de microbiologie, hôpital Le Kremlin- Bicêtre, AP-HP, France.

Helicobacter pylori infection in children. Clinical manifestations are not specific in the course of H. pylori infection in children and in most cases the infection is asymptomatic. The initial diagnosis is based on upper gastrointestinal endoscopy with biopsy-based methods (culture, PCR, histology and rapid urease test). Treatment should be based on the results of the antibiotic (particularly clarithromycin) susceptibility testing of the isolated strains (antibiogram and/or PCR) with a good therapeutic adherence more than 90%. Finally, according to the last pediatric recommendations the treatment duration is 14 days for the triple therapy (proton pump inhibitor + two antibiotics).
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March 2020

Helicobacter pylori Infection in Pediatric Patients Living in Europe: Results of the EuroPedHP Registry 2013 to 2016.

J Pediatr Gastroenterol Nutr 2020 10;71(4):476-483

Pediatric Gastroenterology, Kaplan Medical Centre, Rehovot, Israel.

Objectives: The aim of the study was to assess clinical presentation, endoscopic findings, antibiotic susceptibility and treatment success of Helicobacter pylori (H. pylori) infected pediatric patients.

Methods: Between 2013 and 2016, 23 pediatric hospitals from 17 countries prospectively submitted data on consecutive H. pylori-infected (culture positive) patients to the EuroPedHP-Registry.

Results: Of 1333 patients recruited (55.1% girls, median age 12.6 years), 1168 (87.6%) were therapy naïve (group A) and 165 (12.4%) had failed treatment (group B). Patients resided in North/Western (29.6%), Southern (34.1%) and Eastern Europe (23.0%), or Israel/Turkey (13.4%). Main indications for endoscopy were abdominal pain or dyspepsia (81.2%, 1078/1328). Antral nodularity was reported in 77.8% (1031/1326) of patients, gastric or duodenal ulcers and erosions in 5.1% and 12.8%, respectively. Primary resistance to clarithromycin (CLA) and metronidazole (MET) occurred in 25% and 21%, respectively, and increased after failed therapy. Bacterial strains were fully susceptible in 60.5% of group A, but in only 27.4% of group B. Primary CLA resistance was higher in Southern and Eastern Europe (adjusted odds ratio [ORadj] = 3.44, 95% confidence interval [CI] 2.22-5.32, P < 0.001 and 2.62, 95% CI: 1.63-4.22, P < 0.001, respectively) compared with Northern/Western Europe. Children born outside Europe showed higher primary MET resistance (ORadj = 3.81, 95% CI: 2.25-6.45, P < 0.001). Treatment success in group A reached only 79.8% (568/712) with 7 to 14 days triple therapy tailored to antibiotic susceptibility.

Conclusions: Peptic ulcers are rare in dyspeptic H. pylori-infected children. Primary resistance to CLA and MET is markedly dependent on geographical regions of birth and residence. The ongoing survey will show whether implementation of the updated ESPGHAN/NASPGHAN guidelines will improve the eradication success.
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October 2020

Differences in Management of Eosinophilic Esophagitis in Europe: An Assessment of Current Practice.

J Pediatr Gastroenterol Nutr 2020 07;71(1):83-90

Ghent University Hospital, Ghent, Belgium.

Objectives: The aim of the study was to assess differences in the diagnosis and management of eosinophilic esophagitis (EoE) by European pediatric (PG) and adult gastroenterologists (AG), and their self-reported adherence to guidelines.

Methods: A multiple-choice questionnaire gauged the diagnostic and management strategies of gastroenterologists treating children or adults in 14 European countries and the United Arab Emirates (UAE).

Results: Questionnaires were completed by 465 PG and 743 AG. PG were significantly more likely to take biopsies in patients with symptoms of esophageal dysfunction (86.2% PG vs 75.4% AG, P < 0.001) and to perform endoscopic follow-up (86.3% PG vs 80.6% AG, P < 0.001). After failure of proton-pump inhibitors (PPIs), topical steroids were the preferred second-line therapy; however, PG opted more frequently for elimination diets (47.5% PG vs 13.7% AG, P < 0.001). More PG than AG indicated having read recent guidelines (89.4% PG vs 58.2% AG, P < 0.001). Geographic differences in practice were reported, with respondents from the United Kingdom, Portugal, and Spain more often adhering to recommended biopsy protocols. Physicians in the UAE, France, Lithuania, and Poland tended to opt for steroid therapy or elimination diets as first-line therapy, in contrast to most other countries.

Conclusions: Significant differences in general practice between PG and AG were demonstrated with notable divergence from consensus guidelines. International practice variations are also apparent. Among other strategies, educational activities to highlight current recommendations may help harmonize and optimize clinical practice.
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July 2020

Adapted first-line treatment of infection in Algerian children.

Ann Gastroenterol 2019 Jan-Feb;32(1):60-66. Epub 2018 Oct 3.

Department of Gastroenterology, Queen Fabiola Children's Hospital, Free University of Brussels, Belgium (Zhor Guechi).

Background: () infection is acquired in early life and continues to have a high prevalence, especially in developing countries. Growing antibiotic-resistant strains necessitate adapted treatments. This study aimed to compare the efficacy, side effects, and influence of resistance of strains between two different treatments.

Methods: This prospective, randomized blind study enrolled 112 symptomatic children infected with (66 girls, mean age 11.1 years). Treatments, allocated randomly irrespective of the susceptibility of the strains, were either the standard omeprazole-amoxicillin-clarithromycin combination for 7 days (OAC7; group A) or omeprazole-amoxicillin with a higher dose of metronidazole (40 instead of 20 mg/kg/d) for 10 days (OAM10; group B).

Results: Before treatment, the resistance rates of strains to metronidazole or clarithromycin were 37% and 13%, respectively, with 7% resistant to both antibiotics and neither to amoxicillin. Eradication rates obtained with OAM10 (80% by intention-to-treat [ITT] and 88% by per protocol [PP] analysis) were higher than with OAC7 (68% in ITT and 71% PP) and the differences (12% in ITT and 17% PP) were statistically significant (P=0.03). Successful treatments with OAM10 were obtained in metronidazole resistant strains and were more effective in children aged >10 years (P=0.02 by ITT and P=0.04 by PP). Only light or moderate side effects, mainly digestive, were observed.

Conclusion: Because of its therapeutic efficacy, good tolerance and lower cost the OAM10 can be considered as an appropriate first-line therapeutic scheme in Algeria.
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October 2018

Molecular diagnosis of Helicobacter pylori infection in gastric biopsies: Evaluation of the Amplidiag H. pylori + ClariR assay.

Helicobacter 2019 Apr 12;24(2):e12560. Epub 2018 Dec 12.

Bacteriology, Cochin Hospital, University of Paris-Descartes, Institut Pasteur, Paris, France.

Background: Adapted treatments for Helicobacter pylori infection, guided by determining antimicrobial resistance, are associated with high eradication rates. We evaluated the performance of the Amplidiag H. pylori + ClariR PCR assay (Amplidiag ) for detecting H. pylori and its clarithromycin resistance from gastric biopsies taken during endoscopy in comparison to culture and our "in-house" PCR.

Materials And Methods: A total of 127 gastric biopsies were analyzed (98 adults; 29 children). Culture, PCR Amplidiag , and in-house PCR were performed in parallel. The in-house PCR combined amplification and sequencing of a 267-bp fragment of the H. pylori 23S rRNA gene. Discrepancies were controlled by amplification of glmM gene.

Results: For detection of H. pylori, Amplidiag and the in-house PCR were concordant in 118 of 127 of cases: 66 negative and 52 positive. Discrepancies were observed in nine cases, all with low bacterial load: Amplidiag did not detect seven biopsies positive on in-house PCR but detected two positive biopsies that were negative on in-house PCR. Among the 19 of 52 (36%) H. pylori cases resistant to clarithromycin, only four biopsies with mixed populations exhibited discordant results between the two PCR methods. The A2142T mutation was not detected by Amplidiag . With the in-house PCR and amplified glmM gene as the reference method, the sensitivity and specificity of Amplidiag was 88.5% (95% confidence interval 83-94.1) and 100%.

Conclusion: This study demonstrated the high sensitivity of the PCR-based Amplidiag H. pylori test, especially with low H. pylori load, and the probability of its clarithromycin resistance analysis. For clinical use, a well-designed trial with a large scale of samples may still be needed.
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April 2019

Pediatric Eosinophilic Esophagitis: Results of the European Retrospective Pediatric Eosinophilic Esophagitis Registry (RetroPEER).

J Pediatr Gastroenterol Nutr 2019 04;68(4):552-558

Institute of Gastroenterology, Nutrition, and Liver Disease, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.

Objectives: Recommendations for diagnosing and treating eosinophilic esophagitis (EoE) are evolving; however, information on real world clinical practice is lacking. To assess the practices of pediatric gastroenterologists diagnosing and treating EoE and to identify the triggering allergens in European children.

Methods: Retrospective anonymized data were collected from 26 European pediatric gastroenterology centers in 13 countries. Inclusion criteria were: Patients diagnosis with EoE, completed investigations prescribed by the treating physician, and were on stable medical or dietary interventions.

Results: In total, 410 patients diagnosed between December 1999 and June 2016 were analyzed, 76.3% boys. The time from symptoms to diagnosis was 12 ± 33.5 months and age at diagnosis was 8.9 ± 4.75 years. The most frequent indications for endoscopy were: dysphagia (38%), gastroesophageal reflux (31.2%), bolus impaction (24.4%), and failure to thrive (10.5%). Approximately 70.3% had failed proton pump inhibitor treatment. The foods found to be causative of EoE by elimination and rechallenge were milk (42%), egg (21.5%), wheat/gluten (10.9%), and peanut (9.9%). Elimination diets were used exclusively in 154 of 410 (37.5%), topical steroids without elimination diets in 52 of 410 (12.6%), both diet and steroids in 183 of 410 (44.6%), systemic steroids in 22 of 410 (5.3%), and esophageal dilation in 7 of 410 (1.7%). Patient refusal, shortage of endoscopy time, and reluctance to perform multiple endoscopies per patient were noted as factors justifying deviation from guidelines.

Conclusions: In this "real world" pediatric European cohort, milk and egg were the most common allergens triggering EoE. Although high-dose proton pump inhibitor trials have increased, attempted PPI treatment is not universal.
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April 2019

Performances of the IDEIA HpStAR Stool Antigen Test in Detection of Helicobacter pylori Infection Before and After Eradication Treatment in Algerian Children.

J Trop Pediatr 2019 Jun;65(3):210-216

Service de Pédiatrie, Hôpital N. Hamoud CHU Hussein Dey, Algiers, Algeria.

We aimed to evaluate in an Algerian pediatric population the diagnostic performances of the IDEIA HpStAR noninvasive stool antigen test (Oxoid, Cambridge, UK) to detect Helicobacter pylori infection before and after eradication therapy. A prospective study including 158 symptomatic Algerian children was conducted. Patients were initially diagnosed with invasive (culture, histology, and rapid urease test) and noninvasive tests (urea breath test and IDEIA HpStAR test). Infected patients were treated, and 101 were controlled after treatment with two invasive (culture and histology) and two noninvasive tests (urea breath test and IDEIA HpStAR test). In Algerian children, the IDEIA HpStAR test showed good performances for initial detection of H. pylori infection and also for subsequent control of eradication treatment. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of IDEIA HpStAR test before treatment were 93.6%, 100%, 100%, 87.3%, and 96%, respectively, and those after treatment were 100, 92.8, 78.6, 100, and 94.2%, respectively.
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June 2019

Helicobacter pylori Infection in Pediatric Patients: Update on Diagnosis and Eradication Strategies.

Paediatr Drugs 2018 Aug;20(4):337-351

Department of Pediatric Gastroenterology, Université Libre de Bruxelles, Hôpital Universitaire des Enfants Reine Fabiola, Brussels, Belgium.

Helicobacter pylori infection is acquired mainly in childhood and remains an essential cause of peptic ulcer disease and gastric cancer. This article provides commentary on the last ESPGHAN/NASPGHAN guidelines and on publications made after the consensus conference of 2015. The majority of infected children are asymptomatic and pediatric studies do not support a role for H. pylori in functional disorders such as recurrent abdominal pain. The role of H. pylori infection in failure to thrive, children's growth, type I diabetes mellitus (T1DM), and celiac disease remains controversial. The diagnosis of infection should be based on upper-digestive endoscopy with biopsy-based methods. Eradication control after treatment should be based on validated non-invasive tests. Nodular gastritis is the main endoscopic finding of childhood H. pylori infection, but gastroduodenal erosions/ulcers are seen in some children, especially after 10 years of age. When indicated, eradication treatment should be given when good compliance is expected and based on the antimicrobial susceptibility profile.
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August 2018

Randomized Trial of a Yogurt-type Amino Acid-based Formula in Infants and Children With Severe Cow's Milk Allergy.

J Pediatr Gastroenterol Nutr 2018 01;66(1):135-140

Hôpital Saint Vincent de Paul, Groupement Hôpitaux de l'Institut Catholique de Lille (GHICL), Lille, France.

Objectives: Evaluation of a spoon-fed amino acid-based formula (AAF) with a yogurt-type texture compared to the reference oral liquid formula (Neocate).

Methods: Phase III/IV, prospective, randomized (1:1), open-label, multicenter study in infants/young children (6-36 months) with severe cow's milk protein allergy (CMA) who had consumed AAF for ≥1 month before the study. Patients received reference+test formula (Neocate with a yogurt-type texture for spoon-feeding: group 1) or reference formula (group 2) for 28 days. The study formulae were integrated into the patients' usual daily diet. Efficacy on Day 0, 14, and 28 was assessed primarily in terms of symptoms associated with CMA. The evolution of symptoms, amount of formula consumed, nutritional and energy intake, anthropometric data, and tolerability were also assessed.

Results: The incidence of CMA symptoms was similar in each group (P > 0.05) on day 0, 14, and 28. For specific symptoms, there was little change from day 0 and no significant difference between groups for incidence on day 0 or evolution at day 14 or 28. There was no difference in formula consumption (day 0-day 28) between groups (P = 0.90), but nutritional value was generally higher for group 1 and calcium intake was statistically higher for group 1 (P < 0.05). Weight-for-height, weight-for age, and body mass index-for-age z scores were higher for group 1 than group 2 (P < 0.05). Both formulae were well tolerated.

Conclusions: There was no difference in efficacy, formula consumption, and tolerability between the new spoon-fed yogurt-type AAF formula and the reference formula, whereas significantly higher calcium intake was achieved with the new formula.
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January 2018

Helicobacter pylori infection in children.

Helicobacter 2017 Sep;22 Suppl 1

Department of Microbiology, Cochin Hospital, Assistance Publique Hôpitaux de Paris (AP-HP), University Paris Descartes, Paris, France.

Helicobacter pylori infection in children differs from that in adults, from the point of view of epidemiology, host response, clinical features, related diseases, and diagnosis, as well as treatment strategies. The prevalence of H. pylori infection, in both children and adults, is decreasing in the Western World as well as in some developing countries, which contrasts with the increase in childhood asthma and allergic diseases. Recurrent abdominal pain is not specific during H. pylori infection in children. The role of H. pylori infection and failure to thrive, children's growth, type I diabetes mellitus (T1DM) and celiac disease remains controversial. The main initial diagnosis is based on upper digestive endoscopy with biopsy-based methods. Nodular gastritis may be a pathognomonic endoscopic finding of childhood H. pylori infection. The infection eradication control is based on validated noninvasive tests. The main cause of treatment failure of H. pylori infection is its clarithromycin resistance. We recommend standard antibiotic susceptibility testing of H. pylori in pediatric patients prior to the initiation of eradication therapy. H. pylori treatment in children should be based on an evaluation of the rate of eradication in the local population, a systematic use of a treatment adapted to the susceptibility profile and a treatment compliance greater than 90%. The last meta-analysis in children did not show an advantage for sequential therapy when compared to a 14-day triple therapy. Finally, the high rate of antibiotic resistance responsible for therapy failure in recent years justifies the necessity of a novel vaccine to prevent H. pylori infection in children.
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September 2017

A one-step immune-chromatographic Helicobacter pylori stool antigen test for children was quick, consistent, reliable and specific.

Acta Paediatr 2017 Dec 25;106(12):2025-2030. Epub 2017 Jul 25.

Service de Bactériologie, Hôpital Cochin, Université Paris Descartes, Paris, France.

Aim: This French study assessed a quick, noninvasive, immuno-chromatographic, Helicobacter pylori (H. pylori) stool antigen test for detecting infections in children.

Methods: We enrolled 158 children, with a median age of 8.5 years (range eight months to 17 years), with digestive symptoms suggesting upper gastrointestinal tract disease. Upper digestive endoscopy was performed with gastric biopsy specimens for histology, a rapid urease test, culture test and quantitative real-time polymerase chain reaction. The H. pylori stool antigen test was performed twice for each child and the results were compared to the reference method.

Results: The reference methods showed that 23 (14.6%) of the 158 children tested were H. pylori positive. The H. pylori stool antigen test showed 91.3% sensitivity, with a 95% confidence interval (95% CI) of 86.9-95.6 and 97% specificity (95% CI 94.3-99.6), 30.84 positive likelihood ratio and 0.09 negative likelihood ratio. The test accuracy was 96.2% (95% CI 93.2-99.1). The two blinded independent observers produced identical H. pylori stool antigen test results and the Kappa coefficient for the H. pylori stool antigen test was one.

Conclusion: The H. pylori stool antigen test was found to be a consistent, reliable, quick and specific test for detecting the H. pylori infection in children.
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December 2017

Joint ESPGHAN/NASPGHAN Guidelines for the Management of Helicobacter pylori in Children and Adolescents (Update 2016).

J Pediatr Gastroenterol Nutr 2017 06;64(6):991-1003

*Division of Gastroenterology, Hepatology and Nutrition, Cell Biology Program, Sickkids Toronto, Departments of Paediatrics and Physiology, University of Toronto, Toronto, Canada†Division of Gastroenterology and Hepatology, Dr. von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany‡Department of Medicine and School of Public Health, Centre of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta, Edmonton, Alberta, Canada§Paediatric Gastroenterology Department, Hôpital Universitaire des Enfants Reine Fabiola||Department of Paediatric Gastroenterology, Queen Fabiola University Children's Hospital, Université Libre de Bruxelles, Brussels, Belgium¶Pediatric Gastroenterology, Hepatology, and Nutrition, CLINTEC, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden#Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD**Children's Center for Digestive Healthcare, LLC, Gi Care for Kids, LLC, Children's Healthcare of Atlanta††Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA‡‡Department of Pediatrics, Gastroenterology Division, Marshall University School of Medicine, Huntington, WV§§Faculty of Medicine, Department of Gastroenterology, Hepatology and Nutrition, University Children's Hospital Ljubljana, Ljubljana, Slovenia||||Saint Antoine Pediatric Clinic, Saint Vincent de Paul Hospital, Groupement de l'Institut Catholique de Lille (GH-ICL), Catholic University, Lille, France¶¶Kaplan Medical Center, Hadassah Medical School, Hebrew University, Jerusalem, Israel##Pediatric Gastroenterology Division, Hospital de Pediatría, Centro Medico Nacional Siglo XXI, I.M.S.S. Mexico City, Mexico***Laboratoire de Bactériologie, Université de Bordeaux, Bordeaux, France†††Division of Gastroenterology, Hepatology and Nutrition, First Department of Pediatrics, University of Athens, Children's Hospital "Ag. Sofia", Athens, Greece‡‡‡School of Medicine, University College Dublin, Dublin, Ireland.

Background: Because of the changing epidemiology of Helicobacter pylori infection and low efficacy of currently recommended therapies, an update of the European Society for Paediatric Gastroenterology Hepatology and Nutrition/North American Society for Pediatric Gastroenterology, Hepatology and Nutrition recommendations for the diagnosis and management of H pylori infection in children and adolescents is required.

Methods: A systematic review of the literature (time period: 2009-2014) was performed. Representatives of both societies evaluated the quality of evidence using GRADE (Grading of Recommendation Assessment, Development, and Evaluation) to formulate recommendations, which were voted upon and finalized using a Delphi process and face-to-face meeting.

Results: The consensus group recommended that invasive diagnostic testing for H pylori be performed only when treatment will be offered if tests are positive. To reach the aim of a 90% eradication rate with initial therapy, antibiotics should be tailored according to susceptibility testing. Therapy should be administered for 14 days, emphasizing strict adherence. Clarithromycin-containing regimens should be restricted to children infected with susceptible strains. When antibiotic susceptibility profiles are not known, high-dose triple therapy with proton pump inhibitor, amoxicillin, and metronidazole for 14 days or bismuth-based quadruple therapy is recommended. Success of therapy should be monitored after 4 to 8 weeks by reliable noninvasive tests.

Conclusions: The primary goal of clinical investigation is to identify the cause of upper gastrointestinal symptoms rather than H pylori infection. Therefore, we recommend against a test and treat strategy. Decreasing eradication rates with previously recommended treatments call for changes to first-line therapies and broader availability of culture or molecular-based testing to tailor treatment to the individual child.
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June 2017

How do they stick together? Bacterial adhesins implicated in the binding of bacteria to the human gastrointestinal mucins.

Biochem Soc Trans 2017 04;45(2):389-399

CNRS, UMR 8576, Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), Université Lille, F-59000 Lille, France

The gastrointestinal mucosal surface is the primary interface between internal host tissues and the vast microbiota. Mucins, key components of mucus, are high-molecular-weight glycoproteins characterized by the presence of many -linked oligosaccharides to the core polypeptide. They play many biological functions, helping to maintain cellular homeostasis and to establish symbiotic relationships with complex microbiota. Mucin -glycans exhibit a huge variety of peripheral sequences implicated in the binding of bacteria to the mucosal tissues, thereby playing a key role in the selection of specific species and in the tissue tropism displayed by commensal and pathogenic bacteria. Bacteria have evolved numerous strategies to colonize host mucosae, and among these are modulation of expression of cell surface adhesins which allow bacteria to bind to mucins. However, despite well structurally characterized adhesins and lectins, information on the nature and structure of oligosaccharides recognized by bacteria is still disparate. This review summarizes the current knowledge on the structure of epithelial mucin -glycans and the interaction between host and commensal or pathogenic bacteria mediated by mucins.
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April 2017

Sequential Therapy for Helicobacter pylori Infection in Treatment-naïve Children.

Helicobacter 2016 Apr 30;21(2):106-13. Epub 2015 Jun 30.

Dr. v. Haunersches Kinderspital, Ludwig-Maximilians-University, Munich, Germany.

Unlabelled: The goal of first-line Helicobacter pylori therapy is to reach an eradication rate of 90% to avoid further investigations, antibiotic use, and spreading of resistant strains.

Aim: To evaluate the eradication rate of high-dose sequential therapy in treatment-naïve children and to assess factors associated with failure.

Methods: Prospective data assessed in a registry from nine European centers between October 2009 and December 2011. Children with biopsy-proven Helicobacter pylori infection were prescribed 5 days of esomeprazole and amoxicillin, followed by 5 days of esomeprazole, clarithromycin, and metronidazole according to bodyweight. Eradication was assessed after 8-12 weeks. Primary endpoint was the eradication rate in children who received at least one dose and had follow-up data. Multivariate analysis evaluated potential factors for treatment success including sex, age, center, migrant status, antibiotic resistance, and adherence to therapy.

Results: Follow-up was available in 209 of 232 patients (age range 3.1-17.9 years, 118 females). Primary resistance occurred for clarithromycin in 30 of 209 (14.4%), for metronidazole in 32 (15.3%), for both antibiotics in 7 (3.3%), and culture failed in 6 (2.9%). Eradication was achieved in 168 of 209 children (80.4%, 95% CI 75.02-85.78), in 85.8% with no resistance, 72.6% with single resistance, and 28.6% with double resistance. Independent factors affecting eradication rate included resistance to clarithromycin (adjusted ORs 0.27 (0.09-0.84), p = .024), to metronidazole (0.25 (0.009-0.72), p = .010) or to both (0.04 (0.01-0.35), p = .004), and intake of ≤ 90% of prescribed drugs (0.03 (0.01-0.18), p < .001).

Conclusion: A high-dose 10-day sequential therapy cannot be recommended in treatment-naïve children.
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April 2016

Safety of a New Amino Acid Formula in Infants Allergic to Cow's Milk and Intolerant to Hydrolysates.

J Pediatr Gastroenterol Nutr 2015 Oct;61(4):456-63

*Pediatric Gastroenterology, Hepatology and Nutrition Department, Necker Children's Hospital, Paris, France †Saint Antoine Clinics of Pediatrics, Saint Vincent de Paul Hospital, Groupement des Hôpitaux de l'Institut Catholique, Lille, France ‡Department of Pediatrics, Regional Hospital, Namur, Belgium §Gastroenterology, Hepatology and Nutrition Unit, University and Pediatric Hospital of Lyon, Lyon, France ||Pulmonology and Allergology Department, Regional University Hospital, Strasbourg, France ¶private allergy medical practice, Illkirch-Graffenstaden #private allergy medical practice, Forbach, France **Allergology Department, Queen Fabiola Children's University Hospital, Brussels, Belgium ††Intestinal Ecosystem, Probiotics, Antibiotics (EA4065), Sorbonne Paris Cité, DHU Risks in Pregnancy, Paris Descartes University, Paris, France.

Objectives: Amino acid-based formulas (AAFs) are recommended for children with cow's-milk allergy (CMA) failing to respond to extensively hydrolysed formulas (eHFs). We evaluated the effects of a new thickened AAF (TAAF, Novalac), containing a pectin-based thickener, and a reference AAF (RAAF, Neocate) on allergy symptoms and safety, through blood biochemistry analysis and growth.

Methods: Infants (ages < 18 months) with CMA symptoms failing to respond to eHFs were randomised in a double-blind manner to receive TAAF or RAAF for 3 months. All of the infants were then fed TAAF for 3 additional months. Paediatric visits occurred at 1, 3, and 6 months. Blood samples were collected at inclusion and 3 months.

Results: Results at 1 month were previously described. The 75 infants with proven CMA and eHF intolerance tolerated their allocated formula. At 3 months, the dominant allergic symptom had disappeared in 76.2% of the infants with TAAF and in 51.5% of the infants with RAAF (P = 0.026). The Scoring Atopic Dermatitis Index significantly improved more with TAAF than with RAAF (-27.3 ± 2.3 vs -20.8 ± 2.2, P = 0.048). Of the infants, 92.9% had normal stools (soft or formed consistency) with TAAF vs 75.8% with RAAF (P = 0.051). More infants in TAAF group had better quality of nighttime sleep (P = 0.036) and low frequency of irritability signs (P < 0.001). With both formulas, all of the biochemical parameters were within normal ranges. There were no differences between the 2 groups in any of the anthropometric z scores.

Conclusions: The new TAAF was tolerated by all of the infants with CMA and intolerance to eHFs. Anthropometric and clinical data showed that both formulas were safe.
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October 2015

Usefulness of Gastric Biopsy-Based Real-Time Polymerase Chain Reaction for the Diagnosis of Helicobacter pylori Infection in Children.

J Pediatr Gastroenterol Nutr 2015 Sep;61(3):307-12

*Clinique Pédiatrique St Antoine †Département d'Anatomopathologie, Hôpital St Vincent de Paul ‡Département de Microbiologie, Hôpital St Philibert, Groupement des Hôpitaux de l'Institut Catholique de Lille, Lille §Service de Gastroentérologie Pédiatrique, Hôpital Necker-Enfants-malades, AP-HP ||Service de Microbiologie, Hôpital Cochin, Université Paris V-René Descartes, Paris, France.

Objectives: The aim of the study was to assess the usefulness of gastric biopsy-based quantitative real-time polymerase chain reaction (qPCR) for the detection of Helicobacter pylori infection and the identification of clarithromycin-resistant strains in children.

Methods: A gastric biopsy-based qPCR for the detection of H pylori infection and the identification of clarithromycin-resistant strains in children was evaluated in 62 children with infection and 341 children without infection. H pylori infection was considered by the "reference method" when culture was positive for both histology and rapid urease test (RUT). Results were compared with those obtained using the qPCR.

Results: The reference method versus H pylori qPCR positivity showed 95% confidence interval sensitivity 100% versus 100%, specificity 93.2% (86.9-99.4) versus 100%, positive predictive value 59.7% (47.4-71.9) versus 100%, negative predictive value 100% versus 100%, and, finally, test accuracy of 59.6% (47.3-71.8) versus 100%. Sixty-two children were found to be H pylori positive, based on the qPCR results. Among those, 31 children had both positive qPCR and culture with concordant antimicrobial susceptibility testing results, whereas 31 children had negative culture and positive qPCR. The qPCR showed a bacterial load ≥10 copies per milliliter when culture, histology, and RUT were all positive (29/31 children) versus <10 copies per milliliter when culture, histology, and RUT were all negative (25/31 children). Grades 2 and 3 histological gastritis were associated with a bacterial load ≥10 copies per milliliter for 28/35 of children versus 27/27 of grade 0 to 1 <10 copies per milliliter.

Conclusions: H pylori qPCR positivity is a more precise test than the routine culture, histology, RUT alone and allows detecting low bacterial loads.
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September 2015

Presentation and endoscopic management of sigmoid volvulus in children.

Eur J Pediatr 2015 Jul 28;174(7):965-9. Epub 2015 Jan 28.

Department of Pediatrics, CHC Liège Clinique de L'Espérance, Rue Saint-Nicolas 447-449, 4420, Liège, Belgium,

Unlabelled: The aim of the present study was to evaluate clinical presentation and management of sigmoid volvulus in children, focusing on endoscopic reduction. In this retrospective multicenter study, we reviewed the charts of 13 patients with sigmoid volvulus. We recorded clinical symptoms, diagnostic methods, endoscopic or surgical therapy, and outcome. The children (seven girls, six boys) had a median age of 12.8 years (range, 15 months to 17 years) at initial presentation. Eight patients had associated diseases (e.g., chronic constipation, mental retardation, or myopathy). The initial symptoms were abdominal pain (13/13), abdominal distension (11/13), and vomiting (7/13), which were associated with abdominal tenderness in all patients. Abdominal X-ray showed dilated sigmoid loops and air-fluid levels in all patients. Endoscopic reduction by exsufflation was successful without any complications in 12 patients, whereas the youngest patient underwent a first-line sigmoidectomy. Recurrence occurred in 7/12 patients after endoscopic exsufflation. Finally, 11 patients underwent a sigmoidectomy.

Conclusion: Although rare in children, sigmoid volvulus should be advocated when abdominal pain is associated with dilated sigmoid loops. Sigmoidoscopic exsufflation can be considered as the first-line management in the absence of perforation. However, sigmoidectomy is often required for prevention of recurrence.

What Is Known: • Sigmoid volvulus is uncommon in childhood. • Diagnosis is often missed or delayed. What is New: • This is the first pediatric series showing that endoscopic exsufflation is an efficient and safe treatment option. • Elective sigmoid resection with primary anastomosis is often required to prevent recurrence.
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July 2015

Advances in the treatment of infection in children.

Ann Gastroenterol 2015 Jan-Mar;28(1):10-18

Department of Pediatric Gastroenterology, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, Brussels, Belgium (Patrick Bontems, Samy Cadranel).

In this review we elaborate on two main questions concerning the management of infection in children. First, we focus on who should be treated. In the presence of ()-associated peptic ulcer disease, eradication of the micro-organism is recommended. When infection is detected by biopsy-based methods in the absence of peptic ulcer disease in a child with dyspeptic symptoms, treatment of infection may be considered. In infected children whose first degree relatives have gastric cancer, treatment can be offered. A 'test-and-treat' strategy is not and has never been recommended in children. The second issue to address is what the recommended treatments are. ESPGHAN/NASPGHAN recommends that treatment tailored to susceptibility testing should be the first choice in pediatric patients. The duration of therapy should be 10-14 days. Costs, compliance and adverse effects should be taken into account. Checking the result of eradication with a reliable non-invasive test such as the C urea breath test, is recommended at least 4-8 weeks following completion of therapy.
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May 2014

A thickened amino-acid formula in infants with cow's milk allergy failing to respond to protein hydrolysate formulas: a randomized double-blind trial.

Paediatr Drugs 2014 Dec;16(6):513-22

Pediatric Gastroenterology, Hepatology and Nutrition Department, Necker Children's Hospital, 149, rue de Sèvres, 75015, Paris, France,

Introduction: Amino-acid-based formulas (AAFs) are recommended for children with cow's milk protein allergy (CMPA) failing to respond to extensively hydrolyzed formulas (eHFs).

Objective: This study aimed to assess the tolerance/hypoallergenicity and efficacy of a thickened AAF (TAAF) in these infants.

Methods: This multicenter, double-blind, randomized controlled trial (NCT01940068) compared 3-month feeding with a pectin-based TAAF (Novalac(®), United Pharmaceuticals, Paris, France) and a commercially available "reference" AAF (RAAF; Neocate(®), Nutricia, Germany) in infants aged <18 months with CMPA and persistent allergy symptoms with eHF feeding. Reported here are the results of an interim analysis after 1 month of feeding.

Results: Of the 86 infants randomized, CMPA with eHF intolerance was confirmed in 75 infants; all of them tolerated the allocated AAFs. The major allergic symptom disappeared within 1 month in 61.9 and 51.5 % and regurgitations disappeared in 66.7 and 42.3 % of infants who received TAAF and RAAF, respectively. Infants had significantly more normal stools (soft or formed consistency) with the TAAF (90.5 vs. 66.7 %; p = 0.011). From baseline, daily family life significantly improved with both AAFs: crying time decreased by 97.3 (p < 0.001) and 28.6 min (p = 0.014) and sleeping time increased by 64.6 (p = 0.009) and 29.0 min with TAAF and RAAF, respectively. At day 30, weight and body mass index z-score gains were 0.1 and 0.2 with TAAF and 0.2 and 0.0 with RAAF.

Conclusion: Both AAFs were well tolerated by infants with CMPA and eHF intolerance and ensured appropriate growth, with the TAAF providing additional comfort.
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December 2014

The impact of dietary therapy on clinical and biologic parameters of pediatric patients with eosinophilic esophagitis.

J Allergy Clin Immunol Pract 2014 Sep-Oct;2(5):587-93

Hôpital Necker - Enfants Malades, Université Paris Descartes, Paris, France; Clinique Pédiatrique Saint Antoine, Hôpital Saint Vincent de Paul, Groupement des Hôpitaux de l'Institut Catholique de Lille, France. Electronic address:

Background: Eosinophilic esophagitis (EoE) is a clinicopathologic disease that presents with a massive infiltration of the esophagus by eosinophils triggered by food antigen(s).

Objective: To determine the impact of dietary therapy on nutritional parameters in patients who present with EoE.

Methods: A convenience retrospective study analyzed patients with EoE after a 2-month dietary therapy (6-food elimination diet, avoidance of the 6 most common allergenic foods, plus avoidance of those eliciting positive skin testing, plus amino-acid formula as replacement for dairy products). Pre- and postdiet allergic and nutritional status were evaluated.

Results: Of 111 eligible patients, 59 patients, with a median age of 77.7 months (range, 9-189 months) were enrolled. Dietary therapy significantly increased the return to normal endoscopic appearance (47.4%, P < .0009) and led to complete remission (<5 eosinophils/esophageal HPF and disappearance of symptoms) in 59.3%. All symptoms improved, digestive (98.3%), cutaneous (80%), and respiratory (92.8%). The prediet median weight-for-height (WFH) z score was -0.75 (-3.00 to 5.69), and the postdiet WFH did not significantly differ, -0.51 (-3.09 to 5.00). The prediet WFH z score was less than -2 (moderate malnutrition) in 10.1%. Postdiet blood eosinophils counts decreased in absolute numbers and in counts ≥ 500 × 10(6)/L (P < .0001). Evaluation after 1 year of progressive reintroduction of eliminated foods was available in 33 children: the median WFH z score did not significantly improve, from -0.89 (range, -3.00 to 0.67) at enrollment to -0.59 (range, -3.66 to 2.24).

Conclusion: The nutritional status of children with EoE was mildly affected and not worsened by the 2-month dietary therapy.
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May 2015

Helicobacter pylori Infection in European children with gastro-duodenal ulcers and erosions.

Pediatr Infect Dis J 2013 Dec;32(12):1324-9

From the *Paediatric Gastroenterology-Hepatology, Queen Fabiola Children's University Hospital, Université Libre de Bruxelles, Brussels, Belgium; †Saint Vincent de Paul Hospital, Clinic of Paediatrics St Antoine, Groupement des Hôpitaux de l'Institut Catholique de Lille (GH-ICL), Lille, France; ‡Medical Microbiology Laboratory, Communicable and Infectious Diseases, Scientific Institute of Public Health, Brussels, Belgium; §Department of Paediatrics, Medical University of Wroclaw, Wroclaw, Poland; ¶Department of Paediatrics, Karolinska University Hospital, Stockholm, Sweden; ‖Dr v. Hauner Children's Hospital, University Medical Center, Munich, Germany; **Department of Paediatrics, University of Piemonte Orientale, Novara, Italy; ††Department of Paediatrics, Hospital Universitario Niño Jesús; ‡‡Department of Paediatrics, Hospital 12 de Octobre, Madrid, Spain; §§Academic Medical Center, Amsterdam, The Netherlands; ¶¶Charles University in Prague, Faculty of Medicine in Pilsen, Department of Paediatrics, Prague, Czech Republic; ‖‖First Department of Paediatrics, Semmelweis University, Budapest, Hungary; ***First Department of Paediatrics of Athens University, Athens, Greece; †††Department of Paediatrics, Marmara University Hospital, Istanbul, Turkey; and ‡‡‡Inserm U853, Victor Segalen Bordeaux 2 University, Bordeaux, France.

Background: To analyze risk factors associated with gastro-duodenal ulcers and erosions in children.

Methods: Open, prospective, multicenter, case-control study carried out in 11 European countries in patients with gastric or duodenal ulcers/erosions and 2 age-matched controls each. Possible risk factors were recorded. Logistic regression models were performed with adjustment for centers and age groups.

Results: Seven-hundred thirty-two patients (244 cases, 153 with erosions only and 91 with ulcers, and 488 controls) were recruited. Children receiving antimicrobials or acid suppressive drugs before endoscopy were excluded (202 cases/390 controls remained for risk factor analysis). Helicobacter pylori was detected more frequently in cases than controls but only in 32.0% versus 20.1% in controls (P = 0.001). Independent exposure factors for gastric ulcers were male gender (P = 0.001), chronic neurologic disease (P = 0.015), chronic renal disease (P < 0.001) and nonsteroidal anti-inflammatory drug consumption (P = 0.035). Exposure factors for duodenal ulcers were H. pylori infection (P < 0.001) and steroid consumption (P = 0.031). Chronic renal disease was the only independent factor associated with gastric erosions (P = 0.026), those associated with duodenal erosions being H. pylori infection (P = 0.023), active smoking (P = 0.006) and chronic arthritis (P = 0.008). No risk factor was identified in 97/202 (48.0%) cases.

Conclusions: H. pylori remains a risk factor for duodenal, but not for gastric lesions in children in countries with low prevalence of infection. No risk factor could be identified in half of the children with gastro-duodenal ulcers/erosions.
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December 2013

Intestinal permeability and fecal eosinophil-derived neurotoxin are the best diagnosis tools for digestive non-IgE-mediated cow's milk allergy in toddlers.

Clin Chem Lab Med 2013 Feb;51(2):351-61

Clinique Pediatrique Saint Antoine, Hopital Saint Vincent de Paul, Groupe Hospitalier de L'institut Catholique de Lille, Universite Catholique, Lille, France.

Background: Food allergy is a common problem in France involving 4%-6% of toddlers. As opposed to IgE-mediated cow's milk allergy (CMA), delayed-onset CMA, mostly, non-IgE-mediated, remains difficult to diagnose in toddlers. Our study assessed the diagnostic performances of intestinal permeability and of fecal markers, in comparison with the standard allergic work-up in children referred for CMA diagnosis.

Methods: Twenty-five consecutive children, mean age (standard deviation) 6.3 months (4.8) with digestive and/or extra-digestive manifestations suggesting CMA, were prospectively studied based on a standardized allergic work-up (specific cow's protein IgE and IgG, skin prick test, atopy patch test and oral open cow's milk challenge) and digestive work-up including fecal microbiota analysis, intestinal permeability determination (urinary lactitol/mannitol ratio) and fecal markers measurement, i.e., α(1)-antitrypsin, tumor necrosis factor-α, calprotectin, β-defensin2, secretory IgA and eosinophil-derived neurotoxin (EDN). Receiver operating characteristic (ROC) curves were calculated for all markers in order to define cut-off levels.

Results: The cow's milk challenge was positive in 11 children and negative in 14. The global test performances, i.e., the number of true positive+negative cases/the total number of cases, were 76% for intestinal permeability; 72% for fecal EDN; contrasting with atopy patch test, 68%; IgE, 60%; skin prick test, 55% and IgG, 52%.

Conclusions: In this routine diagnosis allergy work-up for CMA in toddlers, the best efficacy was seen for intestinal permeability compared to IgE, IgG, skin prick test and atopy patch test. Moreover, fecal EDN in a single spot sample displayed a similar performance.
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February 2013

Sequential therapy versus tailored triple therapies for Helicobacter pylori infection in children.

J Pediatr Gastroenterol Nutr 2011 Dec;53(6):646-50

Pediatric Gastroenterology-Hepatology, Queen Fabiola Children's University Hospital, Brussels, Belgium.

Aims: The aim of the study was to compare sequential versus tailored triple therapy regimens on Helicobacter pylori (H pylori) eradication rates in children and to assess the effect of antimicrobial susceptibility.

Patients And Methods: Prospective, open-label, multicenter study. Children received randomly either a 10-day sequential treatment comprising omeprazole (OME) with amoxicillin for 5 days and OME, clarithromycin (CLA), and metronidazole (MET) for the remaining 5 days, or a 7-day triple therapy comprising OME with amoxicillin and CLA in cases of a CLA-susceptible strain or MET in cases of CLA-resistant strain. H pylori eradication was assessed by C-urea breath test.

Results: One hundred sixty-five children, 95 girls and 70 boys, of median age 10.4 years, were included. The intention-to-treat (ITT) eradication rate was 76.9% (sequential 68/83 = 81.9%, triple therapy 59/82 = 71.9%, ns), and the per-protocol (PP) eradication rate was 84.6% (sequential 68/77 = 88.3%, triple therapy 59/73 = 81.8%, ns). Eradication rates tended to be higher using the sequential treatment, but the difference was only statistically significant for ITT analysis in children harboring both CLA- and MET-susceptible strains (87.8% vs 68.5%, odds ratio [OR] 3.3, P = 0.03). Both ITT and PP eradication rates were significantly lower with sequential treatment in CLA-resistant compared with CLA-susceptible strains (ITT: 56.2% vs 72.7%, OR 5.5, P = 0.008; PP 64.3% vs 80.0%, OR 7.9, P = 0.009). Both treatments were well tolerated.

Conclusions: Sequential treatment is greatly effective for eradicating H pylori in children except in CLA-resistant strains. Sequential treatment can be used as a first-line therapy, but only in areas with a low CLA resistance rate.
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December 2011

HLA-DQ genotyping combined with serological markers for the diagnosis of celiac disease: is intestinal biopsy still mandatory?

J Pediatr Gastroenterol Nutr 2011 Jun;52(6):729-33

Gastroentérologie Pédiatrique, Hôpital des Enfants, Bordeaux, France.

Objectives: The aim of this study was to evaluate the value of HLA-DQ2/DQ8 allelic genotyping combined with serologic testing for the diagnosis of celiac disease (CD).

Patients And Methods: One hundred seventy children, who underwent jejunal biopsy for digestive symptoms or malnutrition, were tested for HLA-DQ2/DQ8 and serologic markers (tTG and/or anti-endomysial antibodies). Children were classified in 2 groups, according to jejunal histology: group 1, when partial or total villous atrophy was associated with an increased intraepithelial lymphocytosis suggesting CD, and group 2, when these histological criteria were absent.

Results: Eight children were excluded from the study because their intestinal histology was not informative; 82 children were classified in group 1 and 80 in group 2. Eighty-one of 82 children in group 1 were positive for HLA and serologic testing. The other child had negative HLA and serologic testing but marked villous atrophy, and further investigation showed an allergic disease. Among the 80 children in group 2, 53 were negative for both HLA and serologic testing, 22 were positive for HLA but negative for serologic testing, 2 were negative for HLA and positive for serologic testing, and 3 patients were positive for both HLA and serologic testing. The last 3 children were shown to have an autoimmune background and had probably a latent form of CD. The association of HLA-DQ2/DQ8 and serologic markers had a sensitivity of 98.8%, a specificity of 96.2%, a positive likelihood ratio of 26.3, and a negative likelihood ratio of 0.013.

Conclusions: The association of positive HLA-DQ2/DQ8 and serologic testing has a high predictive value for CD. We suggest that symptomatic children with high titers of immunoglobulin (Ig)A tTG could be diagnosed as patients with CD without performing jejunal biopsy. In other children, HLA-DQ2/DQ8 could be useful to exclude the diagnosis of CD if negative. In cases of low IgA tTG titers or in patients with IgA deficiency, intestinal biopsy remains mandatory.
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June 2011

Evidence-based guidelines from ESPGHAN and NASPGHAN for Helicobacter pylori infection in children.

J Pediatr Gastroenterol Nutr 2011 Aug;53(2):230-43

Dr von Haunersches Kinderspital, Ludwig-Maximilians-University of Munich, Munich, Germany.

Objective: As the clinical implications of Helicobacter pylori infection in children and adolescents continue to evolve, ESPGHAN and NASPGHAN jointly renewed clinical guidelines using a standardized evidence-based approach to develop updated recommendations for children and adolescents in North America and Europe.

Methods: An international panel of 11 pediatric gastroenterologists, 2 epidemiologists, 1 microbiologist, and 1 pathologist was selected by societies that developed evidence-based guidelines based on the Delphi process with anonymous voting in a final face-to-face meeting. A systematic literature search was performed on 8 databases of relevance including publications from January 2000 to December 2009. After excluding nonrelevant publications, tables of evidence were constructed for different focus areas according to the Oxford classification. Statements and recommendations were formulated in the following areas: whom to test, how to test, whom to treat, and how to treat. Grades of evidence were assigned to each recommendation based on the GRADE system.

Results: A total of 2290 publications were identified, from which 738 were finally reviewed. A total of 21 recommendations were generated, and an algorithm was proposed by the joint committee providing evidence-based guidelines on the diagnostic workup and treatment of children with H pylori infection.

Conclusions: These clinical practice guidelines represent updated, best-available evidence and are meant for children and adolescents living in Europe and North America, but they may not apply to those living on other continents, particularly in developing countries with a high H pylori infection rate and limited health care resources.
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August 2011