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Background Food protein‐induced enterocolitis syndrome (FPIES) is a non‐IgE‐mediated food allergy, with potential dehydration secondary to vomiting. Differences exist regarding culprit foods, and age of tolerance depending on the country of origin. We aimed at describing the characteristics of a French population of children with FPIES, and define risk factors for failure during challenge. Methods Data from 179 children who were referred for FPIES in two pediatric tertiary centers between 2014 and 2020 were retrospectively collected. The diagnosis of FPIES was based on international consensus guidelines. Clinical characteristics, culprit food, and age at resolution were assessed. Tolerance was defined as no adverse reaction after OFC or accidental exposure. Results In the 192 described FPIES, the age at first symptoms was 5.8 months old. The main offending foods were cow's milk (60.3%), hen's egg (16.2%), and fish (11.7%). Single FPIES was observed in 94.4% and multiple FPIES in 5.6% of cases. The age at resolution of FPIES was 2.2 years old, and resolution occurred later for fish than for milk (2.9 years vs. 2.0, p = 0.01). Severe acute FPIES was a risk factor for delayed resolution (RR: 3.3 [1.2–9.2]), but not IgE sensitization. Performing a food challenge within 12 months after the first reaction increased the risk of failure (OR: 2.6 [1.1–6.6]). Conclusion In this French cohort of children with FPIES, the main culprit foods were ubiquitous. Rice, oat, and soy were rarely or not involved. Multiple FPIES was infrequent. Our data confirmed the overall good prognosis of FPIES, the later resolution of FPIES to fish and in the case of severe acute FPIES.

The first objective of infant formulas is to ensure the healthy growth of neonates and infants, as the sole complete food source during the first months of life when a child cannot be breastfed. Beyond this nutritional aspect, infant nutrition companies also try to mimic breast milk in its unique immuno-modulating properties. Numerous studies have demonstrated that the intestinal microbiota under the influence of diet shapes the maturation of the immune system and influences the risk of atopic diseases in infants. A new challenge for dairy industries is, therefore, to develop infant formulas inducing the maturation of immunity and the microbiota that can be observed in breastfed delivered vaginally, representing reference infants. Streptococcus thermophilus, Lactobacillus reuteri DSM 17938, Bifidobacterium breve (BC50), Bifidobacterium lactis Bb12, Lactobacillus fermentum (CECT5716), and Lactobacillus rhamnosus GG (LGG) are some of the probiotics added to infant formula, according to a literature review of the past 10 years. The most frequently used prebiotics in published clinical trials are fructo-oligosaccharides (FOSs), galacto-oligosaccharides (GOSs), and human milk oligosaccharides (HMOs). This review sums up the expected benefits and effects for infants of pre-, pro-, syn-, and postbiotics added to infant formula regarding the microbiota, immunity, and allergies.

Background Neutropenic enterocolitis (NE) is a severe digestive complication of chemotherapy, primarily affecting patients with acute myeloid leukemia (AML). We hypothesized that NE is linked to intestinal barrier dysfunction and gut dysbiosis. Methods Sixty-five AML patients undergoing induction chemotherapy were included in this prospective monocentric cohort. Among them, 26 patients (40%) were diagnosed with NE. Stool samples were subjected to bacterial load quantification (all bacteria quantitative PCR), 16s rRNA metagenomic analysis, and short-chain-fatty-acids quantification. Additionally, fecal calprotectin and human 𝛃-defensin 2 along with plasmatic inflammatory cytokines, and citrulline levels were measured. Human transcriptomic analysis was conducted on samples obtained from anatomical specimens of colectomies of NE patients. Results Gut microbiota underwent significant alterations after chemotherapy, transitioning from a diverse and balanced enterotype to enterotypes exhibiting a reduced α-diversity, an increased abundance of Enterococcus faecalis , and a decreased abundance of butyrate-producing genera, which correlated with a decreased fecal concentration of butyrate. Simultaneously, post-chemotherapy, plasma citrulline concentrations decreased indicating enterocyte damages. Finally, human transcriptomic analysis found a significant upregulation of the JAK-STAT signaling KEGG pathway in the colons of NE patients encompassing cytokines (IL-6, OSM-OSMR) that play a pivotal role in sustaining local inflammation within the digestive tract. Conclusions This work reaffirms the significant influence of chemotherapy on the gut microbiota and the integrity of the enterocyte barrier. Severe NE is marked by the development of a local inflammatory response that may be induced by the reduction in butyrate levels. Trial registration The study was registered on Clinicaltrials.gov (identifier: NCT04438278). Graphical Abstract

BackgroundThe use of molecular allergens have greatly improved the clinical relevance of specific IgE serologies during allergy work-up. Very little is known regarding the added value of molecular allergens in the results of the basophil activation test (BAT).ObjectiveTo study the BAT concordance when using similar amounts of molecular allergens against source extracts, and to assess factors associated with BAT discrepancies between extract and related component.MethodsSystematic retrospective monocentric study of all BAT performed at the Trousseau Hospital, Paris, France, with both molecular components and corresponding extract.ResultsData from 213 interpretable extract/component BAT pairs (89 cow milk, 70 wheat, 28 house dust mites (HDM), 12 peanut, 9 hen egg, 3 peach, 1 apple, 1 chicken meat), corresponding to 150 blood samples from 109 patients were analyzed. Among BAT pairs showing allergen sensitizations, the two reagents only showed moderate agreement (κ = 0.62), with 18% (36/201) discordant BAT results. Among 36 cases of discrepant BAT results between extract and molecular component, 69% (25/36) were extract+/component– (p=0.03), in line with genuine allergic status, in contrast with the opposite case. Even in extract+/component+ concordant cases, component-stimulated basophils showed 6% less activation rates than their extract-stimulated counterpart. After stratification by allergen, better performances were confirmed with cow milk extract, but not with other allergens, which display large disparity regarding the propensity of different molecular component to activate basophils. Independently of the considered allergen, other variables such as total IgE, BAT positive control values, and treatment with monoclonal antibody or allergen-specific immunotherapy, appear to further modulate the risk of presenting a discordant BAT result.ConclusionIn our study population, molecular components had lower capacity than the corresponding extract to activate IgE-sensitized basophils, which partly explain higher rates of true positive extract+/component– BAT. Component-based BAT can potentially lead to false-negative results, and extract-based should generally be preferred, especially for cow milk.

Background: Hydrolysed rice formula (HRF) is tolerated by >90% of children with cow’s milk protein allergy (CMPA). However, concerns have been raised about potential suboptimal growth in infants fed HRF compared to those fed an extensively hydrolysed milk protein formula (eHF). Aims: To compare growth, safety and tolerance acquisition in infants with CMPA when fed HRF versus eHF. Methods: A multicentre prospective, randomised, double-blind, placebo-controlled food challenge trial was conducted with infants with CMPA. The infants received either HRF or eHF over a 12-month follow-up period. The primary outcome measure was the change from baseline over the study period in weight-for-length expressed as a Z-score. The secondary outcomes were other anthropometric measurements, tolerability and adverse events (AEs). Results: In total, 105 children were enrolled. The weight-for-length measurements were −0.01 (HRF) and −0.29 (eHF) at baseline and 0.29 and 0.05, respectively, at the last visit, with no significant between-group difference (p = 0.28; mixed-effects model). The Z-scores for other anthropometric variables indicated normal growth, with no significant between-group differences. In total, 29 potentially product-related AEs were reported (12 in the HRF group and 17 in the eHF group). A trend was observed toward a faster acquisition of tolerance in the HRF group (median age: 20.4 months) compared to the eHF group (16.3 months), but this was not statistically significant (p = 0.18). Conclusions: HRF demonstrated appropriate growth, acquisition of tolerance and a good safety profile in infants with CMPA, with no significant differences versus eHF. HRF could be considered as an appropriate option in the management of CMPA.

In children, CMV-associated protein-losing enteropathy (PLE) is characterised by a benign course and spontaneous healing but can lead to generalised oedema. Poorly defined, it is diagnosed after unnecessary invasive tests. Children with CMV-associated PLE between 2009 and 2019 in two French hospitals are retrospectively described. Clinical and biological signs, CMV identification, endoscopy and histological findings, disease management and course are analysed. CMV-associated PLE is proven in 21 immunocompetent and 22 immunosuppressed patients, with ages consistent with primo-infection and reactivation, respectively. The digestive symptoms prevail in immunocompetent children, mainly with vomiting (85.7% versus 50%, CI [1.2; 39.2], p = 0.02). Immunocompetent patients show more oedema (61.9% versus 4.5%, CI [3.6; 1502.4], p < 0.001), linked to more severe hypoalbuminemia (21.2 g/L [17.6–25.7] versus 29.6 g/L [24.9–33.9], p = 0.01). A severe course is observed in 23.8% of the immunocompetent patients and 54.5% of the immunosuppressed ones (p = 0.06). Evidence of CMV infection based on non-invasive methods is found on 88.9% of immunocompetent and 95.5% of immunosuppressed patients (p = 0.58), while endoscopy was performed on 95.2% and 100% of them, respectively (p = 0.48), without any therapeutic change. Thus, CMV-associated PLE should be suspected in children with generalised oedema. Not as benign as previously described, it can be confirmed using non-invasive tests.

Background Provided they are accessible and of high quality, childcare centres may help in addressing social inequalities in health. The \"Accompagne-moi…!” (AM) approach was developed to improve the quality of these centres in France. It aimed at improving professional practices to help children develop their social and emotional skills, and was evaluated in a pilot study which analysed its viability conditions in France. Methods A qualitative study was conducted in 14 childcare centres of four deprived areas in France over the 2019–2022 period. Eight interviews were conducted with stakeholders who initiated the approach, followed by 33 semi-structured interviews with childcare professionals. Results The childcare centres interviewed were characterised by involved professionals working in challenging conditions, which were exacerbated during the health crisis. AM had the potential to meet certain needs (e.g. professional training) and to produce positive effects (e.g. a less stressful environment). However, the challenges of deploying such an intervention in highly stressed environments resulted in some professionals reporting a negative experience, such as a feeling of failure or loneliness. The viability conditions of AM were therefore highlighted, such as the need for sufficient human resources, integration of the approach into childcare centre projects, collective ownership of the approach, and supportive management and organisation. Conclusion While it is essential to consider the emotions of the children in childcare centres, the results emphasise how the well-being of children must be considered alongside to the well-being of professionals. Although it needs to be adapted before being scaled up, the AM approach has the potential to contribute to high-quality early childhood education. Some structural determinants are essential to implement interventions such as AM without creating difficulties for professionals.

Managing everyday wellness using sensors requires user buy-in and acceptance. The Unified Theory of Acceptance and Use of Technology (UTAUT) was used to measure at D-0 the acceptability (a priori), and at D-21 the acceptance of an ambulatory monitoring system under development, the SHERPAM system. Interviews with the participants revealed that they no longer viewed the system in the same way at the different stages of the study. The results of the qualitative analysis suggest that the time of the research led the participants to stop seeing themselves as potential future users and to take on the role of critical testers of the technology (which corresponds more to a user test). This role change led participants to question the usefulness of the technology, which affected their intention to use the technology in the future (5.30 vs. 4.24; t = 2.58 *). This research identified the reasons why it was crucial to have a fully functional device in the second phase (acceptance study). The results of this study suggest that it is inappropriate to undertake an acceptability study when the technology is under development. While the SHERPAM platform has been the subject of several user tests, none have been carried out in a situation of use. Thus, this study seems to suggest that the dysfunctions observed are more related to the absence of a development phase in the daily activity of the users. Thus, to ensure a good appropriation of the technology and to predict its use, the technology must not only be in perfect working order, but must also have been developed according to the daily activities of the individuals.

Mucopolysaccharidosis type I-H (MPS I-H) is a rare lysosomal storage disorder caused by α-L-Iduronidase deficiency. Early haematopoietic stem cell transplantation (HSCT) is the sole available therapeutic option to preserve neurocognitive functions. We report long-term follow-up (median 9 years, interquartile range 8–16.5) for 51 MPS I-H patients who underwent HSCT between 1986 and 2018 in France. 4 patients died from complications of HSCT and one from disease progression. Complete chimerism and normal α-L-Iduronidase activity were obtained in 84% and 71% of patients respectively. No difference of outcomes was observed between bone marrow and cord blood stem cell sources. All patients acquired independent walking and 91% and 78% acquired intelligible language or reading and writing. Intelligence Quotient evaluation (n = 23) showed that 69% had IQ ≥ 70 at last follow-up. 58% of patients had normal or remedial schooling and 62% of the 13 adults had good socio-professional insertion. Skeletal dysplasia as well as vision and hearing impairments progressed despite HSCT, with significant disability. These results provide a long-term assessment of HSCT efficacy in MPS I-H and could be useful in the evaluation of novel promising treatments such as gene therapy.

PurposeThe purpose of this study is to assess the efficacy of 153Sm-EDTMP (Quadramet®) in a clinical setting.MethodsWe have conducted a retrospective study of all consecutive patients (pts) treated with 153Sm-EDTMP for painful bone metastases. At each visit (before and after treatment), four parameters were collected: (i) pain assessment according to the 10-step visual analogue scale (VAS), (ii) sleep disturbance related to pain, (iii) dose of analgesic medication, and (iv) answer to the following closed question “Do you think you obtained a benefit from treatment?” Success of treatment was defined by the combination of these four parameters.ResultsThree hundred seventy consecutive 153Sm-EDTMP treatments for painful bone metastases were given. Patients had the following primary tumors: breast carcinoma (153), prostate carcinoma (155), lung carcinoma (27), or other cancers (35). Fifty-eight percent of the patients had received previous external osseous radiotherapy. Ninety-seven percent of the patients were treated with concomitant analgesics and 61% were treated with diphosphonates. A clinical benefit was described in 55.0% of cases at D30. Treatment was more effective in cases of breast and prostate cancers compared with other types of primary cancers. Patients described a benefit at D30 in 62, 58, 6, and 38% of cases of breast, prostate, lung, and other cancers. The subjective efficacy was accompanied by a decrease in analgesic intake in 35.0% of cases.Conclusion153Sm-EDTMP therapy is an effective supportive treatment in patients who suffer from bone metastases, especially in patients with breast or prostate cancer.