The p.E152K-STIM1 mutation deregulates Ca2+ signaling contributing to chronic pancreatitis.

Since deregulation of intracellular Ca2+ can lead to intracellular trypsin activation, and stromal interaction molecule-1 (STIM1) protein is the main regulator of Ca2+ homeostasis in pancreatic acinar cells, we explored the Ca2+ signaling in 37 STIM1 variants found in three pancreatitis patient cohorts. Extensive functional analysis of one particular variant, p.E152K, identified in three patients, provided a plausible link between dysregulated Ca2+ signaling within pancreatic acinar cells and chronic pancreatitis susceptibility. Specifically, p.E152K, located within the STIM1 EF-hand and sterile α-motif domain, increased the release of Ca2+ from the endoplasmic reticulum in patient-derived fibroblasts and transfected HEK293T cells. This event was mediated by altered STIM1-sarco/endoplasmic reticulum calcium transport ATPase (SERCA) conformational change and enhanced SERCA pump activity leading to increased store-operated Ca2+ entry (SOCE). In pancreatic AR42J cells expressing the p.E152K variant, Ca2+ signaling perturbations correlated with defects in trypsin activation and secretion, and increased cytotoxicity after cholecystokinin stimulation.This article has an associated First Person interview with the first author of the paper.

Comparison of Endoscopic Dilatation and Heller's Myotomy for Treating Esophageal Achalasia in Children: A Multicenter Study.

OBJECTIVE: To compare the efficacy of, and complications from, the 2 main treatments for achalasia: endoscopic dilatation and surgical cardiomyotomy (Heller's myotomy). STUDY DESIGN: We retrospectively collected data on children treated for achalasia over an 11-year period from 8 tertiary pediatric centers. A line of treatment was defined as performing either Heller's myotomy or 1-3 sessions of endoscopy dilatation over 3 months. Treatment success was a priori defined as clinical improvement and no need for new treatment. RESULTS: Ninety-seven children (median age, 12 years; 57% boys) were included. The median time to diagnosis was 10.5 months, and the median follow-up period was 27 months. Thirty-seven children were treated by Heller's myotomy and 60 by endoscopy dilatation as the first-line treatment. After adjustment for potentially confounding factors, Heller's myotomy was significantly more successful than endoscopy dilatation (hazard ratio, 3.93 [1.74; 8.88]; P = .001), with a median survival without failure of 49 and 7 months, respectively, and with no significant difference in the occurrence of complications (35.2% for Heller's myotomy, 29.7% for endoscopy dilatation, P = .56). Hydrostatic dilatation was as successful as pneumatic dilatation (hazard ratio, 1.35 [0.56; 3.23]; P = .50). CONCLUSIONS: Heller's myotomy is more successful than endoscopy dilatation, with no significant difference in the occurrence of serious complications. This raises the potential role of peroral endoscopic myotomy as an alternative treatment to Heller's myotomy.

Faecal calprotectin and gut microbiota do not predict enteropathy in very preterm infants.

AIM: Very preterm birth is associated with a high risk of enteropathies. Diagnosis is challenging, especially in mild forms, leading to unnecessary periods of cessation of enteral feeding. This study aimed at establishing a prognosis score of enteropathy combining clinical parameters and faecal calprotectin concentration. METHODS: This prospective multicentric study included preterm neonates born at a gestational age of 33 weeks or less. Stools were collected weekly until hospital discharge, and daily in case of digestive events for calprotectin measurement (ELISA and immunochromatography) and microbiota analyses (16S rRNA gene sequencing). RESULTS: Among the 121 neonates included, 21 experienced at least one episode of enteropathy, mainly mild forms. By ELISA testing, median faecal calprotectin was 88 (8-798) µg/g faeces. No statistically significant association was found between the outset of enteropathy and maternal and neonatal characteristics, and calprotectin levels. The agreement between ELISA and immunochromatography assay was moderate (intra-class correlation coefficient 0.58, 95%CI [0.47-0.66]). Comparison of species diversity and relative bacterial abundance profiles between infants with or without enteropathy revealed no specific alterations associated with enteropathy. CONCLUSION: The study failed to propose a prognostic score of enteropathy, probably due the large inter- and intra-individual variability of faecal calprotectin in very preterm neonates.

Genetic characterization of congenital tufting enteropathy: epcam associated phenotype and involvement of SPINT2 in the syndromic form.

Congenital tufting enteropathy (CTE) is a rare and severe enteropathy recently ascribed to mutations in the epcam gene. Here we establish SPINT2, previously ascribed to congenital sodium diarrhea, as a second gene associated with CTE and report molecular and immunohistochemistry data in 57 CTE patients. Inclusion criteria were early onset diarrhea and intestinal insufficiency with the typical histological CTE abnormalities. The clinical phenotype was registered, the entire coding regions of epcam and SPINT2 sequenced, and immunostaining of EpCAM and SPINT2 performed on intestinal biopsies. An epcam mutation was involved in 41 patients (73 %) who mainly displayed isolated digestive symptoms. Mutations severely affected gene expression since the EpCAM signal on intestinal tissues was either undetectable or low and irregular. Twelve other patients (21 %) carried mutations in SPINT2, and were phenotypically characterized by systematic association with keratitis (p < 10(-4)) and, for half of them, with choanal atresia (p < 10(-4)). Dependency on parenteral nutrition (PN) was comparable in patients with epcam or SPINT2 mutations, but the frequent epcam mutation c.556-14A>G (abnormal splicing) was significantly associated with a better outcome (p = 0.032) with milder PN dependency to weaning in some cases. Finally, four patients (7 %) with isolated digestive symptoms had no detectable epcam or SPINT2 mutation. Two candidate genes, Elf3 and Claudin7, were excluded from this population. Our study allows us to separate CTE patients into at least three genetic classes, each with specific phenotypes. The genetics approach raises the question of the distinction between two congenital enteropathies. Our findings should help improve the diagnosis of CTE, guide toward strategies of long-term PN management, and limit indications for intestinal transplantation to life-threatening PN complications.

Clinical decision support system in emergency telephone triage: A scoping review of technical design, implementation and evaluation.

OBJECTIVES: Emergency department overcrowding could be improved by upstream telephone triage. Emergency telephone triage aims at managing and orientating adequately patients as early as possible and distributing limited supply of staff and materials. This complex task could be improved with the use of Clinical decision support systems (CDSS). The aim of this scoping review was to identify literature gaps for the future development and evaluation of CDSS for Emergency telephone triage. MATERIALS AND METHODS: We present here a scoping review of CDSS designed for emergency telephone triage, and compared them in terms of functional characteristics, technical design, health care implementation and methodologies used for evaluation, following the PRISMA-ScR guidelines. RESULTS: Regarding design, 19 CDSS were retrieved: 12 were knowledge based CDSS (decisional algorithms built according to guidelines or clinical expertise) and 7 were data driven (statistical, machine learning, or deep learning models). Most of them aimed at assisting nurses or non-medical staff by providing patient orientation and/or severity/priority assessment. Eleven were implemented in real life, and only three were connected to the Electronic Health Record. Regarding evaluation, CDSS were assessed through various aspects: intrinsic characteristics, impact on clinical practice or user apprehension. Only one pragmatic trial and one randomized controlled trial were conducted. CONCLUSION: This review highlights the potential of a hybrid system, user tailored, flexible, connected to the electronic health record, which could work with oral, video and digital data; and the need to evaluate CDSS on intrinsic characteristics and impact on clinical practice, iteratively at each distinct stage of the IT lifecycle.

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

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, ß-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.

Putting undergraduate medical students in AI-CDSS designers' shoes: An innovative teaching method to develop digital health critical thinking.

INTRODUCTION: Digital health programs are urgently needed to accelerate the adoption of Artificial Intelligence and Clinical Decision Support Systems (AI-CDSS) in clinical settings. However, such programs are still lacking for undergraduate medical students, and new approaches are required to prepare them for the arrival of new and unknown technologies. At University Paris Cité medical school, we designed an innovative program to develop the digital health critical thinking of undergraduate medical students that consisted of putting medical students in AI-CDSS designers' shoes. METHODS: We followed the six steps of Kern's approach for curriculum development: identification of needs, definition of objectives, design of an educational strategy, implementation, development of an assessment and design of program evaluation. RESULTS: A stand-alone and elective AI-CDSS program was implemented for fourth-year medical students. Each session was designed from an AI-CDSS designer viewpoint, with theoretical and practical teaching and brainstorming time on a project that consisted of designing an AI-CDSS in small groups. From 2021 to 2022, 15 students were enrolled: they rated the program 4.4/5, and 80% recommended it. Seventy-four percent considered that they had acquired new skills useful for clinical practice, and 66% felt more confident with technologies. The AI-CDSS program aroused great enthusiasm and strong engagement of students: 8 designed an AI-CDSS and wrote two scientific 5-page articles presented at the Medical Informatics Europe conference; 4 students were involved in a CDSS research project; 2 students asked for a hospital internship in digital health; and 1 decided to pursue PhD training. DISCUSSION: Putting students in AI-CDSS designers' shoes seemed to be a fruitful and innovative strategy to develop digital health skills and critical thinking toward AI technologies. We expect that such programs could help future doctors work in rapidly evolving digitalized environments and position themselves as key leaders in digital health.

Assessment of local and systemic signature of eosinophilic esophagitis (EoE) in children through multi-omics approaches.

Background: Eosinophilic oesophagitis (EoE) is a chronic food allergic disorder limited to oesophageal mucosa whose pathogenesis is still only partially understood. Moreover, its diagnosis and follow-up need repeated endoscopies due to absence of non-invasive validated biomarkers. In the present study, we aimed to deeply describe local immunological and molecular components of EoE in well-phenotyped children, and to identify potential circulating EoE-biomarkers. Methods: Blood and oesophageal biopsies were collected simultaneously from French children with EoE (n=17) and from control subjects (n=15). Untargeted transcriptomics analysis was performed on mRNA extracted from biopsies using microarrays. In parallel, we performed a comprehensive analysis of immune components on both cellular and soluble extracts obtained from both biopsies and blood, using flow cytometry. Finally, we performed non-targeted plasma metabolomics using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Uni/multivariate supervised and non-supervised statistical analyses were then conducted to identify significant and discriminant components associated with EoE within local and/or systemic transcriptomics, immunologic and metabolomics datasets. As a proof of concept, we conducted multi-omics data integration to identify a plasmatic signature of EoE. Results: French children with EoE shared the same transcriptomic signature as US patients. Network visualization of differentially expressed (DE) genes highlighted the major dysregulation of innate and adaptive immune processes, but also of pathways involved in epithelial cells and barrier functions, and in perception of chemical stimuli. Immune analysis of biopsies highlighted EoE is associated with dysregulation of both type (T) 1, T2 and T3 innate and adaptive immunity, in a highly inflammatory milieu. Although an immune signature of EoE was found in blood, untargeted metabolomics more efficiently discriminated children with EoE from control subjects, with dysregulation of vitamin B6 and various amino acids metabolisms. Multi-blocks integration suggested that an EoE plasma signature may be identified by combining metabolomics and cytokines datasets. Conclusions: Our study strengthens the evidence that EoE results from alterations of the oesophageal epithelium associated with altered immune responses far beyond a simplistic T2 dysregulation. As a proof of concept, combining metabolomics and cytokines data may provide a set of potential plasma biomarkers for EoE diagnosis, which needs to be confirmed on a larger and independent cohort.

Towards a Clinical Decision Support System for Helping Medical Students in Emergency Call Centers.

In critical situations such as pandemic, medical students are often called to help in emergency call centers. However, they may encounter difficulties in phone triage because of a lack of medical skills. Here, we aim at developing a Clinical Decision Support System for helping medical students in phone call triage of pediatric patients. The system is based on the PAT (Pediatric Assessment Triangle) and local guidelines. It is composed of two interfaces. The first allows a quick assessment of severity signs, and the second provides recommendations and additional elements such as "elements to keep in mind" or "medical advice to give to patient". The system was evaluated by 20 medical students, with two fictive clinical cases. 75% of them found the content useful and clear, and the navigation easy. 65% would feel more reassured to have this system in emergency call centers. Further works are planned to improve the system before implementation in real-life.

An Interactive Interface for Displaying Recommendations on Emergency Phone Triage in Pediatrics.

Emergency phone triage aims at identifying quickly patients with critical emergencies. Patient triage is not an easy task, especially in situations involving children, mostly due to the lack of training and the lack of clinical guidelines for children. To overcome these issues, we aim at designing and assessing an interactive interface for displaying recommendations on emergency phone triage in pediatrics. Four medical students formalized local guidelines written by the SAMU of Paris, into a decision tree and designed an interface according to usability principles. The navigation within the interface was designed to allow the identification of critical emergencies at the beginning of the decision process, and thus ensuring a quick response in case of critical emergencies. The interface was assessed by 10 medical doctors: they appreciated the ergonomics (e.g., intuitive colors), and found easy to navigate through the interface. Nine of them would like to use this interface during phone call triage. In the future, this interface will be improved and implemented in emergency call centers.

Isolation and Characterization of Commensal Bifidobacteria Strains in Gut Microbiota of Neonates Born Preterm: A Prospective Longitudinal Study.

Bifidobacterial population dynamics were investigated using a longitudinal analysis of dominant species isolated from feces of neonates born preterm (singletons (n = 10), pairs of twins (n = 11)) from birth up to 16 months of age. We performed quantification, isolation, and identification of the dominant bifidobacteria strains. The genetic relationship of the isolates was investigated via pulsed field gel electrophoresis (PFGE) genotyping, and PCR was used to screen the specific genetic marker tet genes. Additionally, all of the isolated strains were phenotypically characterized by their response to gastro-intestinal stresses and the MIC determination of tetracycline. In the same individual, our results showed a turnover of the bifidobacteria dominant population not only at species but also at strain levels. In addition, we found clonally related strains between twins. A minority of strains were tolerant to gastric (6%) and intestinal (16%) stresses. Thirteen percent of the strains were resistant to tetracycline. This work is original as it provides insights at the strain level of the early life in vivo dynamics of gut microbiota bifidobacteria in preterm neonates. It highlights the need to take into consideration the fluctuation of bifidobacteria populations that may occur for one individual.

A fermented formula in pre-term infants: clinical tolerance, gut microbiota, down-regulation of faecal calprotectin and up-regulation of faecal secretory IgA.

Intestinal bacterial colonisation in pre-term infants is delayed compared with full-term infants, leading to an increased risk of gastrointestinal disease. Modulation of colonisation through dietary supplementation with probiotics or prebiotics could decrease such a risk. The present study evaluated clinical tolerance, the effects on gut microbiota, and inflammatory and immunological mucosal responses to an infant formula adapted for pre-term infants that included in its manufacturing process a fermentation step with two probiotic strains, Bifidobacterium breve C50 and Streptococcus thermophilus 065, inactivated by heat at the end of the process. A total of fifty-eight infants (gestational age: 30-35 weeks), fed either the fermented pre-term formula or a standard pre-term formula, were followed up during their hospital stay. Clinical tolerance, faecal microbiota using a culture and a culture-independent method (temporal temperature gel electrophoresis), faecal calprotectin and secretory IgA were analysed weekly. No difference was observed regarding anthropometric data and digestive tolerance, except for abdominal distension, the incidence of which was lower in infants fed the fermented formula for 2 weeks. Bacterial colonisation was not modified by the type of feeding, particularly for bifidobacteria. Faecal calprotectin was significantly lower in infants fed the fermented formula for 2 weeks, and secretory IgA increased with both mother's milk and the fermented formula. The fermented formula was well tolerated and did not significantly modulate the bacterial colonisation but had benefits on inflammatory and immune markers, which might be related to some features of gastrointestinal tolerance.

The use of biofeedback for children with fecal incontinence secondary to retentive constipation: Experience of a French Pediatric Center.

BACKGROUND: Fecal incontinence (FI) secondary to chronic retentive constipation is a frequent demand in pediatric gastroenterology clinics. The management of constipation in children includes laxatives (polyethylene glycol, PEG), enhanced toilet training, and dietary advice. Biofeedback is a possible treatment for children above the age of 7 years with resistant FI. AIM: To analyze any changes in volume to trigger defecation (VTD) and envy score over the course of biofeedback sessions according to clinical response. METHODS: In this retrospective study, we reviewed the medical records of 23 children diagnosed with FI according to the Rome IV criteria and treated with biofeedback. For each biofeedback session, a mean VTD by subject was measured. At the end, therapy was considered a success if soiling disappeared and a failure if any persisted. The need to defecate expressed by the child was described as an envy score. A 0-10 visual analog scale was used to express the intensity of this sensation. Follow-up involved calling the parents 12 months after the biofeedback sessions had ended to assess symptoms remotely. RESULTS: The study included 19 boys and 4 girls with a median age of 10 years. Patients' ages ranged between 7 and 17 years. None of them had any associated neurological disorders. All children had FI for >1 year. The median number of soiling episodes per week was 7. The average number of biofeedback sessions was 3 (range 1-5). At the end of the rehabilitation sessions, 12 children (52%) were in the "success" group. In the latter, median VTD decreased from 97 ml to 70 ml between the first and last session. In the "failure" group, VTD decreased from 120 ml to 100 ml. The between-group difference in the median VTD at the first session was not statistically significant. The last observation carried forward (LOCF) VTD was significantly lower in the "success" group compared to the "failure" group (70 ml versus 100 ml, p = 0.03). Median envy scores decreased during the biofeedback sessions with no statistical difference between the groups at the last session. Follow-up of children in the "success" group one year after the last biofeedback session revealed that 10 patients had no relapse (83%) and 2 were lost to follow-up. CONCLUSIONS: Biofeedback might be an effective tool for the management of FI resistant to medical treatment in children.

Enteral tube feeding in patients receiving dietary treatment for metabolic diseases: A retrospective analysis in a large French cohort.

CONTEXT: A strictly controlled diet (often involving enteral tube feeding (ETF)) is part of the treatment of many inherited metabolic diseases (IMDs). OBJECTIVE: To describe the use of ETF in a large cohort of patients with IMDs. DESIGN: A retrospective analysis of ETF in patients with urea cycle disorders (UCDs), organic aciduria (OA), maple syrup disease (MSUD), glycogen storage diseases (GSDs) or fatty acid oxidation disorders (FAODs) diagnosed before the age of 12 months. SETTING: The reference center for IMDs at Necker Hospital (Paris, France). RESULTS: 190 patients born between January 1991 and August 2017 were being treated for OA (n = 60), UCDs (n = 55), MSUD (n = 32), GSDs (n = 26) or FAODs (n = 17). Ninety-eight of these patients (52%) received ETF (OA subgroup: n = 40 (67%); UCDs: n = 12 (22%); MSUD: n = 9 (28%); GSDs: n = 23 (88%); FAODs: n = 14 (82%)). Indications for ETF were feeding difficulties in 64 (65%) patients, cessation of fasting in 39 (40%), and recurrent metabolic decompensation in 14 (14%). Complications of ETF were recorded in 48% of cases, more frequently with nasogastric tube (NGT) than with gastrostomy. Among patients in whom ETF was withdrawn, the mean duration of ETF was 5.9 (SD: 4.8) years (range: 0.6-19.8 years). The duration of ETF was found to vary from one disease subgroup to another (p = 0.051). While the longest median duration was found in the GSD subgroup (6.8 years), the shortest one was found in the UCD subgroup (0.9 years). CONCLUSION: ETF is an integral part of the dietary management of IMDs. The long duration of ETF and the specific risks of NGT highlights the potential value of gastrostomy.In this study at a French tertiary hospital, we documented the indications, modalities, duration and complications of enteral tube feeding in a cohort of patients with inherited metabolic diseases.

Faecal calprotectin in term and preterm neonates.

OBJECTIVES: The aim of this review was to examine the characteristics of the faecal calprotectin assay in neonates and the evidence for its use as a noninvasive marker of intestinal illnesses during the neonatal period. METHODS: Bibliographic searches were performed in the MEDLINE electronic database up to February 2010 looking for the following words (all fields): "infants" or "neonates" and "calprotectin." Twenty studies, in which 1180 neonates were enrolled, were selected. RESULTS: During the neonatal period, calprotectin levels are characterized by significantly higher values in both healthy full-term and preterm infants during their first year of life compared with reference values established for children and adults. No difference was observed according to gestational age or birth weight, whereas a higher faecal calprotectin level was detected during intestinal distress in neonates with either inflammatory or patent digestive alterations. Despite high interindividual variations, cutoff levels are proposed to identify infants with a high risk of intestinal illnesses. CONCLUSIONS: Compared with adults and children, healthy full-term and preterm neonates have high calprotectin levels. The measurement of calprotectin levels in faeces can be a promising noninvasive clinical screening test for intestinal distress in neonates.

Functional Gastrointestinal Disorders in Outpatients Aged up to 12 Months: A French Non-Interventional Study.

BACKGROUND: The aim of this study was to estimate the frequency of functional gastrointestinal disorders (FGIDs) in infants aged up to 12 months according to the new ROME IV criteria defining these disorders, and to describe the management of FGIDs in France. METHODS: This French non-interventional, cross-sectional, and multicenter study was conducted among private-outpatient physicians who each included four consecutive patients aged up to 12 months. The frequency of FGIDs was described using the ROME IV criteria versus clinicians' diagnosis. The characteristics of infants with and without FGID were compared, and the management of the FGIDs was described. RESULTS: In the 1722 infants analyzed, the following frequencies were observed according to the ROME IV criteria versus the physicians' diagnosis: regurgitation 41% versus 45%; colic 18% versus 30%; constipation 9% versus 19%; diarrhea 3% versus 8%. Of note, FGID infants were less frequently exclusively breastfeeding at the maternity hospital (p < 0.001), were introduced to cow's milk earlier after leaving the maternity hospital (p < 0.001), and more frequently had symptoms suggestive of cow's milk protein allergy (p < 0.001). Physicians frequently recommended an adapted infant formula (in 77% to 82% of cases depending on the FGID diagnosed) and prescribed a specific treatment in 51% to 66% of infants (probiotics: 35% to 64%). CONCLUSIONS: This real-world study confirms the high frequency of FGIDs in infants in France, and provides new information regarding the characteristics of FGID infants.

Urgent endoscopy in children: epidemiology in a large region of France.

Background and study aims The real burden of urgent endoscopy in children has not been studied yet. Our aim was to evaluate the need for urgent endoscopy in children. Patients and methods Information was collected about all the calls that were received during the 24 hour on-call shift for pediatric endoscopy in the region of Ile-de-France (12.1 million inhabitants) during a 6 months period (February-July 2017). Results A total of 237 calls (19 calls/y/100,000 children) were collected regarding children of an average age of 3.2 years (range 2 days-18 years). Most of the calls (68 %) were for foreign body ingestions. Gastroscopy was required in 32 % of children: 24 % of those calling for foreign body ingestion, 48 % for gastrointestinal bleeding, 63 % for caustic ingestions ( P  = 0.01). The average time between the call and the urgent endoscopy were below the international recommendations for each situation. Conclusions Calling the endoscopist seems to have become a recurrent practice, although in most cases, urgent endoscopy did not appear necessary, especially for foreign body ingestion. This organization of pediatric endoscopy on call was able to guarantee the performance of urgent endoscopy in adequate timing for a highly populated region.

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

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.