Colonic Basidiobolomycosis—An Unusual Presentation of Eosinophilic Intestinal Inflammation

Basidiobolomycosis is a rare fungal disease caused by Basidiobolus ranarum. Involvement of the gastrointestinal tract is unusual and poses both a diagnostic and therapeutic challenge, as clinical signs are non-specific and predisposing risk factors are lacking. It can mimick inflammatory bowel disease, primary immunodeficiency, or a malignancy and should be considered in patients who do not respond to standard therapy. We present the case of a 22 months old boy with confirmed colonic Basidiobolomycosis, who presented with severe eosinophilic inflammation of the gastrointestinal tract. Panfungal PCR performed on DNA extracted directly from a tissue sample confirmed the presence of Basidiobolus. He made a full recovery with a combination of surgery and prolonged targeted antifungal medication

Immunomodulatory effects of amino acid-based formulae (AAF) in gastrointestinal non-IgE mediated food allergy

RATIONALE: Management of non-IgE mediated food allergies in early childhood involves allergen avoidance by using extensively hydrolysed (eHF) or amino acid-based formulas (AAF). Clinical anecdote suggests that AAF relieve symptoms more effectively in some patients than using eHF or simple allergen avoidance. This study aimed to explore whether AAF has additional immunomodulatory properties. METHODS: Forty-eight pediatric patients

Assessment and interpretation of vitamin and trace element status in sick children: a position paper from the European Society for Paediatric Gastroenterology Hepatology Committee in Nutrition

Assessment of vitamin and trace element status (VTE) is important in the clinical management of the sick child. In this position paper, we present the various assessment methods available to the clinical practitioner, and critically discuss pitfalls with interpretation of their results. There are 4 main approaches to assess the VTE body status of an individual patient including clinical examination, dietary assessment, and measurement of direct and indirect biomarkers of VTE in biological samples. Clinical signs of VTE deficiencies usually present only when body stores are substantially depleted and are often difficult to detect or differentiate from other nonnutrient-related causes. In isolation, dietary assessment of micronutrients can be inaccurate and imprecise, in disease and in individual patient assessment but may be useful to complement findings from other VTE assessment methods. Use of biomarkers is the most common approach to assess VTE status in routine practice but in the presence of systemic inflammatory response and in the absence of appropriate paediatric reference intervals, interpretation of biomarker results might be challenging and potentially mislead clinical practice. The use of a multimodal approach, including clinical examination, dietary assessment, and laboratory biomarkers is proposed as the optimal way to ascertain the VTE status of individual patients. In the presence of acute inflammatory conditions, VTE measurements in plasma should be replaced by biomarkers not affected by systemic inflammatory response or delayed until inflammatory state is resolved

An ESPGHAN Position Paper on the Use of Low-FODMAP Diet in Pediatric Gastroenterology

International audienceExcluding oligo-, di-, monosaccharides and polyols (FODMAPs) from the diet is increasingly being used to treat children with gastrointestinal complaints. The aim of this position paper is to review the available evidence on the safety and efficacy of its use in children and provide expert guidance regarding practical aspects in case its use is considered. Members of the Gastroenterology Committee, the Nutrition Committee and the Allied Health Professionals Committee of the European Society for Pediatric Gastroenterology Hepatology and Nutrition contributed to this position paper. Clinical questions regarding initiation, introduction, duration, weaning, monitoring, professional guidance, safety and risks of the diet are addressed. A systematic literature search was performed from 2005 to May 2021 using PubMed, MEDLINE and Cochrane Database of Systematic Reviews. In the absence of evidence, recommendations reflect the expert opinion of the authors. The systematic literature search revealed that the low-FODMAP diet has not been comprehensively studied in children. Indications and contraindications of the use of the diet in different pediatric gastroenterological conditions are discussed and practical recommendations are formulated. There is scarce evidence to support the use of a low-FODMAP diet in children with Irritable Bowel Syndrome and no evidence to recommend its use in other gastrointestinal diseases and complaints in children. Awareness of how and when to use the diet is crucial, as a restrictive diet may impact nutritional adequacy and/or promote distorted eating in vulnerable subjects. The present article provides practical safety tips to be applied when the low-FODMAP diet is considered in children

Convergent somatic evolution commences in utero in a germline ribosomopathy.

Clonal tracking of cells using somatic mutations permits exploration of clonal dynamics in human disease. Here, we perform whole genome sequencing of 323 haematopoietic colonies from 10 individuals with the inherited ribosomopathy Shwachman-Diamond syndrome to reconstruct haematopoietic phylogenies. In ~30% of colonies, we identify mutually exclusive mutations in TP53, EIF6, RPL5, RPL22, PRPF8, plus chromosome 7 and 15 aberrations that increase SBDS and EFL1 gene dosage, respectively. Target gene mutations commence in utero, resulting in a profusion of clonal expansions, with only a few haematopoietic stem cell lineages (mean 8, range 1-24) contributing ~50% of haematopoietic colonies across 8 individuals (range 4-100% clonality) by young adulthood. Rapid clonal expansion during disease transformation is associated with biallelic TP53 mutations and increased mutation burden. Our study highlights how convergent somatic mutation of the p53-dependent nucleolar surveillance pathway offsets the deleterious effects of germline ribosomopathy but increases opportunity for TP53-mutated cancer evolution

Convergent somatic evolution commences in utero in a germline ribosomopathy

Acknowledgements: J.N. is supported by a Cancer Research UK Fellowship and work in the J.N. lab is supported by the Wellcome Trust, Cancer Research UK, Alborada Trust, Rosetrees Trust and the MPN Research Foundation. Work in the D.G.K. laboratory is supported by a European Research Council Starting Grant (ERC-2016-STG-715371), the Bill and Melinda Gates Foundation (INV-002189 and INV-038816) and a Cancer Research UK Programme Foundation Award (DCRPGF\100008). A.J.W. was supported by a Blood Cancer UK Programme Continuity Grant (21002 to A.J.W.), the UK Medical Research Council (MR/T012412/1), the Kay Kendall Leukaemia Fund, Rosetrees Trust, the SDS Foundation, the Shwachman-Diamond Project, the Butterfly Guild, SDS UK, the Connor Wright Project, the Cambridge National Institute for Health Research Biomedical Research Centre and the European Cooperation in Science and Technology (COST) Action CA18233 “European Network for Innovative Diagnosis and treatment of Chronic Neutropenias, EuNet INNOCHRON” and CA21154, “Translational control in Cancer European Network, TRANSLACORE”. Samples were provided by the Cambridge Blood and Stem Cell Biobank, which is supported by the Cambridge NIHR Biomedical Research Centre, Wellcome Trust-MRC Stem Cell Institute and the Cambridge Experimental Cancer Medicine Centre, UK. The authors would also like to thank the individuals for donating the samples that have been used in this study.Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011199; Grant(s): ERC-2016-STG-715371AbstractClonal tracking of cells using somatic mutations permits exploration of clonal dynamics in human disease. Here, we perform whole genome sequencing of 323 haematopoietic colonies from 10 individuals with the inherited ribosomopathy Shwachman-Diamond syndrome to reconstruct haematopoietic phylogenies. In ~30% of colonies, we identify mutually exclusive mutations in TP53, EIF6, RPL5, RPL22, PRPF8, plus chromosome 7 and 15 aberrations that increase SBDS and EFL1 gene dosage, respectively. Target gene mutations commence in utero, resulting in a profusion of clonal expansions, with only a few haematopoietic stem cell lineages (mean 8, range 1-24) contributing ~50% of haematopoietic colonies across 8 individuals (range 4-100% clonality) by young adulthood. Rapid clonal expansion during disease transformation is associated with biallelic TP53 mutations and increased mutation burden. Our study highlights how convergent somatic mutation of the p53-dependent nucleolar surveillance pathway offsets the deleterious effects of germline ribosomopathy but increases opportunity for TP53-mutated cancer evolution.</jats:p

Convergent somatic evolution commences in utero in a germline ribosomopathy

Abstract Clonal tracking of cells using somatic mutations permits exploration of clonal dynamics in human disease. Here, we perform whole genome sequencing of 323 haematopoietic colonies from 10 individuals with the inherited ribosomopathy Shwachman-Diamond syndrome to reconstruct haematopoietic phylogenies. In ~30% of colonies, we identify mutually exclusive mutations in TP53, EIF6, RPL5, RPL22, PRPF8, plus chromosome 7 and 15 aberrations that increase SBDS and EFL1 gene dosage, respectively. Target gene mutations commence in utero, resulting in a profusion of clonal expansions, with only a few haematopoietic stem cell lineages (mean 8, range 1-24) contributing ~50% of haematopoietic colonies across 8 individuals (range 4-100% clonality) by young adulthood. Rapid clonal expansion during disease transformation is associated with biallelic TP53 mutations and increased mutation burden. Our study highlights how convergent somatic mutation of the p53-dependent nucleolar surveillance pathway offsets the deleterious effects of germline ribosomopathy but increases opportunity for TP53-mutated cancer evolution

Convergent somatic evolution commences in utero in a germline ribosomopathy.

Acknowledgements: J.N. is supported by a Cancer Research UK Fellowship and work in the J.N. lab is supported by the Wellcome Trust, Cancer Research UK, Alborada Trust, Rosetrees Trust and the MPN Research Foundation. Work in the D.G.K. laboratory is supported by a European Research Council Starting Grant (ERC-2016-STG-715371), the Bill and Melinda Gates Foundation (INV-002189 and INV-038816) and a Cancer Research UK Programme Foundation Award (DCRPGF\100008). A.J.W. was supported by a Blood Cancer UK Programme Continuity Grant (21002 to A.J.W.), the UK Medical Research Council (MR/T012412/1), the Kay Kendall Leukaemia Fund, Rosetrees Trust, the SDS Foundation, the Shwachman-Diamond Project, the Butterfly Guild, SDS UK, the Connor Wright Project, the Cambridge National Institute for Health Research Biomedical Research Centre and the European Cooperation in Science and Technology (COST) Action CA18233 “European Network for Innovative Diagnosis and treatment of Chronic Neutropenias, EuNet INNOCHRON” and CA21154, “Translational control in Cancer European Network, TRANSLACORE”. Samples were provided by the Cambridge Blood and Stem Cell Biobank, which is supported by the Cambridge NIHR Biomedical Research Centre, Wellcome Trust-MRC Stem Cell Institute and the Cambridge Experimental Cancer Medicine Centre, UK. The authors would also like to thank the individuals for donating the samples that have been used in this study.Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011199; Grant(s): ERC-2016-STG-715371Clonal tracking of cells using somatic mutations permits exploration of clonal dynamics in human disease. Here, we perform whole genome sequencing of 323 haematopoietic colonies from 10 individuals with the inherited ribosomopathy Shwachman-Diamond syndrome to reconstruct haematopoietic phylogenies. In ~30% of colonies, we identify mutually exclusive mutations in TP53, EIF6, RPL5, RPL22, PRPF8, plus chromosome 7 and 15 aberrations that increase SBDS and EFL1 gene dosage, respectively. Target gene mutations commence in utero, resulting in a profusion of clonal expansions, with only a few haematopoietic stem cell lineages (mean 8, range 1-24) contributing ~50% of haematopoietic colonies across 8 individuals (range 4-100% clonality) by young adulthood. Rapid clonal expansion during disease transformation is associated with biallelic TP53 mutations and increased mutation burden. Our study highlights how convergent somatic mutation of the p53-dependent nucleolar surveillance pathway offsets the deleterious effects of germline ribosomopathy but increases opportunity for TP53-mutated cancer evolution