Accuracy in Diagnosis of Celiac Disease Without Biopsies in Clinical Practice

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Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens

Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection

Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study

BackgroundThe PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice.MethodsFebrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed.FindingsOf 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92-5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07-7.59), Group A streptococcus (OR 2.73, 95% CI 1.13-6.09) and E. coli (OR 2.7, 95% CI 1.02-6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11-0.46), influenza B (OR 0.12, 95% CI 0.02-0.37) and RSV (OR 0.16, 95% CI: 0.06-0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23-0.72) and EBV (OR 0.71, 95% CI 0.56-0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively.InterpretationMost febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics.FundingEU Horizon 2020 grant 668303

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Jejunalsonden bei Kindern und Jugendlichen

<jats:title>Zusammenfassung</jats:title><jats:p>Die Ernährung über eine jejunale Sonde wird immer häufiger bei jenen Kindern notwendig, deren kalorischer Bedarf durch gastrale Ernährung nicht ausreichend gedeckt werden kann. Ursächlich hierfür können die Intoleranz gastral zugeführter Nahrung oder eine ausgeprägte gastroösophageale Refluxkrankheit (GÖRK) sein. Da nach Anlage der Jejunalsonde häufig regelmäßige Sondenwechsel notwendig werden, ist eine jejunale Sonde oft nur eine vorübergehende Lösung bis zur perkutanen Anlage eines Jejunostomas (mit oder ohne Antirefluxoperation) oder als Alternative vor einer etwaigen Antirefluxoperation.</jats:p><jats:p>Bevor eine jejunale Sonde gelegt wird, sollte eine Nahrungsintoleranz aufgrund anatomischer oder nicht gastrointestinal bedingter Probleme ausgeschlossen werden.</jats:p><jats:p>Die Versorgung eines Kindes, bei dem die Anlage einer jejunalen Sonde geplant ist, sollte durch ein multidisziplinäres Team, bestehend aus u. a. einem Kindergastroenterologen/einer Kindergastroenterologin, einer Ernährungsfachkraft, einem Psychologen/einer Psychologin und einem Logopäden/einer Logopädin, erfolgen. Das multidisziplinäre Team sollte bereits vor Indikationsstellung die Nahrung anpassen, das Kind logopädisch evaluiert haben und die Familie psychologisch und medizinisch mitbetreuen.</jats:p><jats:p>Eine adäquate Planung, welche auch ethische Aspekte beinhaltet, garantiert, dass sowohl der Patient/die Patientin, die Eltern und Betreuungspersonen wie auch das behandelnde Team ein klares Verständnis der Indikation und Gründe für die Anlage einer jejunalen Sonde haben. Dabei sollten auch die Fortsetzung einer möglichen oralen Ernährung und eine Sondenentwöhnung diskutiert werden.</jats:p><jats:p>Diese Übersicht beinhaltet Handlungsempfehlungen zur Indikationsstellung für den Einsatz jejunaler Sonden, gepaart mit praktischen Überlegungen, welche die Verwendung und die Sicherheit der jejunalen Sondenernährung im Kindes- und Jugendalter optimieren sollen.</jats:p&gt

Jejunal tube feeding in children and adolescents

Jejunal tube feeding is increasingly becoming the standard of care for children in whom gastric tube feeding is insufficient to fulfil caloric needs. Jejunal tube feeding is defined as postpyloric feeding through a feeding tube with its tip placed distally to the Treitz ligament. The jejunal tube bypasses the stomach when gastric feeding is not tolerated or is associated with unacceptable complications including significant gastroesophageal reflux disease. There is growing evidence suggesting that feeding by jejunal tube is a safe and effective means of enteral feeding in children and adolescents; however, because of the frequent need for tube maintenance and replacement leading to increased morbidity, gastrojejunal tube feeding is more a temporary alternative to, for example, cutaneous jejunostomy and antireflux surgery. A number of factors should be considered before placement of a jejunal or a gastrojejunal tube. The symptoms of feeding failure, such as nausea, vomiting, gagging, retching and volume intolerance may be caused by anatomical or nongastrointestinal problems, which will need to be dealt with before considering placement of a jejunal tube. The decision to place a jejunal tube has to be made by a multidisciplinary team, working in close cooperation and providing active follow-up and care. The management of a child awaiting a jejunal feeding tube should begin well before its insertion. The multidisciplinary team should be familiar with and have access to a range of alternative strategies to the insertion of a jejunal feeding tube. These may include food or regimen changes, specific feeding therapy, speech and swallowing assessments and access to psychological support. The team should include a pediatric gastroenterologist, a dietitian, a psychologist, and a speech and language therapist. Adequate planning, including discussion of ethical issues, guarantees that all parties have a clear understanding of the indications and rationale for placement of a jejunal tube. In addition, ongoing and future strategies to increase possible oral feeding and enable weaning off the jejunal tube should be discussed. The aim of this article is to provide a comprehensive guide for healthcare professionals on the safe, effective, and appropriate use of jejunal feeding tubes in children and adolescents

Training in pediatric neurogastroenterology and motility across Europe: a survey of the ESPGHAN National Societies Network 2016-2019

Background: Pediatric gastrointestinal motility disorders present significant challenges for diagnosis and management, emphasizing the need for appropriate training in Pediatric Neurogastroenterology and Motility (PNGM). The aim of this survey, part of a comprehensive survey on training in pediatric gastroenterology, hepatology and nutrition, was to evaluate training related to PNGM across European training centers. Method: Standardized questionnaires were collected from training centers through the National Societies Network of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), from June 2016 to December 2019. Results: In total, 100 training centers from 19 countries participated in the survey. Dedicated PNGM clinics were available in 22 centers; pH-monitoring in 60; pH/impedance in 66; standard manometry in 37; and high-resolution manometry in 33. If all motility studies were performed partially or fully by the trainees, the median (range) annual numbers/per trainee were as follows: pH-monitoring 30 (1-500); pH/impedance 17 (1-131); standard manometries 10 (1-150); and high-resolution manometries 8 (1-75). The motility assessment was performed by pediatric gastroenterologists (43 centers); adult gastroenterologists (10 centers); pediatric surgeons (5 centers); and both pediatric gastroenterologists and pediatric surgeons (9 centers). Annual numbers ≤10 for pH-monitoring, pH/impedance, standard manometries and high-resolution manometries were reported by 7 (12%), 15 (23%), 11 (30%) and 14 (42%) centers, respectively. Conclusions: Significant differences exist in PNGM-related infrastructure, staff and procedural volumes at training centers across Europe. ESPGHAN and the National Societies should take initiatives to ensure the acquisition of competence in PNGM-related knowledge and skills, and develop strategies for assessment and accreditation.An infographic is available for this article at: http://www.annalsgastro.gr/files/journals/1/earlyview/2022/Infographic-AG6486.pdf

Pediatric endoscopy training across Europe: a survey of the ESPGHAN National Societies Network 2016–2019

Background and study aims The ability to perform endoscopy procedures safely and effectively is a key aspect of quality clinical care in Pediatric Gastroenterology, Hepatology and Nutrition (PGHN). The aim of this survey, which was part of a global survey on PGHN training in Europe, was to assess endoscopy training opportunities provided across Europe. Methods Responses to standardized questions related to endoscopy training were collected from training centers across Europe through the presidents/representatives of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition National Societies from June 2016 to December 2019. Results A total of 100 training centers from 19 countries participated in the survey. In 57 centers, the endoscopy suit was attached to the PGHN center, while in 23, pediatric endoscopies were performed in adult endoscopy facilities. Ninety percent of centers reported the availability of specialized endoscopy nurses and 96 % of pediatric anesthetists. Pediatric endoscopies were performed by PGHN specialists in 55 centers, while 31 centers reported the involvement of an adult endoscopist and 14 of a pediatric surgeon. Dividing the number of procedures performed at the training center by the number of trainees, ≤ 20 upper, lower, or therapeutic endoscopies per trainee per year were reported by 0 %, 23 %, and 56 % of centers, respectively, whereas ≤ 5 wireless capsule endoscopies per trainee per year by 75 %. Only one country (United Kingdom) required separate certification of competency in endoscopy. Conclusions Differences and deficiencies in infrastructure, staffing, and procedural volume, as well as in endoscopy competency assessment and certification, were identified among European PGHN training centers limiting training opportunities in pediatric endoscopy

Training in Paediatric Clinical Nutrition Across Europe:A Survey of the National Societies Network (2016-2019) of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition

Objectives/background: Disease-related malnutrition is common in patients with chronic diseases and has detrimental effects, therefore, skills in nutrition care are essential core competencies for paediatric digestive medicine. The aim of this survey, conducted as part of a global survey of paediatric gastroenterology, hepatology and nutrition (PGHN) training in Europe, was to assess nutrition care-related infrastructure, staff, and patient volumes in European PGHN training centres. Methods: Standardized questionnaires related to clinical nutrition (CN) care were completed by representatives of European PGHN training centres between June 2016 and December 2019. Results: One hundred training centres from 17 European countries, Turkey, and Israel participated in the survey. Dedicated CN clinics exist in 66% of the centres, with fulltime and part-time CN specialists in 66% and 42%, respectively. Home tube feeding (HTF) andhome parenteral nutrition (HPN) programmes are in place in 95% and 77% of centres, respectively. Twenty-four percent of centres do not have a dedicated dietitian and 55% do not have a dedicated pharmacist attached to the training centre. Even the largest centres with >5000 outpatients reported that 25% and 50%, respectively do not have a dedicated dietitian or pharmacist. Low patient numbers on HTF and HPN of <5 annually are reported by 13% and 43% of centres, respectively. Conclusions: The survey shows clear differences and deficits in Clinical Nutrition training infrastructure, including staff and patient volumes, in European PGHN training centres, leading to large differences and limitations in training opportunities in Clinical Nutrition