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关键词： Gastric   Development   Organoids   Regenerative medicine  

摘要： Purpose Knowledge of gastric epithelial homeostasis remains incomplete, lacking human-specific models for study. This study establishes a protocol for deriving gastric epithelial organoids from paediatric gastric biopsies, providing a platform for modelling disease and developing translational therapies. Methods Full-thickness surgical samples and endoscopic mucosal biopsies were obtained from six patients. Gastric glands were isolated by a chemical chelation protocol and then plated in 3D culture in Matrigel(R) droplets in chemically defined medium. After formation, organoids were passaged by single cell dissociation or manual disaggregation. Cell composition and epithelial polarity of organoids were assessed by bright field microscopy and immunofluorescence analysis, comparing them to native paediatric gastric tissue. Results Gastric glands were successfully isolated from all six patients who were aged 4 months to 16 years. Gastric glands from all patients sealed to form spherical gastric organoids. These organoids could be passaged by manual disaggregation or single cell dissociation, remaining proliferative up to 1 year in culture. Organoids retained normal epithelial cell polarity, with the apical surface orientated towards the central lumen. Organoids expressed markers of mature gastric epithelial cell types, except for parietal cells. Conclusion Gastric organoids can be reliably generated from paediatric biopsies and are a representative in vitro model for studying gastric epithelium.

关键词： Post-specialty training curriculum   Paediatric and Adolescent Gynaecology   Subspecialty training   EURAPAG   Competency based   Portfolio  

摘要： Interest in the field of Paediatric and Adolescent Gynaecology (PAG) has increased substantially over the last decade. Currently there is minimal consensus on how to interpret and validate professional experience, medical knowledge and surgical skills for doctors (accredited in Obstetrics and Gynaecology) who have an interest in and wish to achieve sub-specialisation in PAG. The challenge for the future of PAG is to create a framework of guidelines and references which in turn culminates in improvement and harmonisation in PAG healthcare delivery. The development of a post-specialty training curriculum in PAG for accredited practitioners was a logical next step after EBCOG introduced the PACT curriculum for OBGYN trainees. The guiding principle in the development of the PAG curriculum has been to strive for harmonisation in teaching and training in PAG within Europe. The new EURAPAG curriculum is divided in 17 chapters which in turn have been subdivided into medical and surgical sections plus a baseline skills section. The content has been determined through a consensus procedure amongst European gynaecologists and trainees. The medical chapters involve pathology that requires conservative treatment, prevention, education or lifestyle adjustment. The chapters that are both medical and surgical have a surgical (alternative) treatment ranging fro mvaginal procedures to advanced hysteroscopic and laparoscopic procedures and laparotomy. Currently, the framework for any medical education is workplace based competency training. Specific tools have been developed for workplace based assessments, such as direct observation (DO) of clinical task performance, Objective Structured Assessment of Technical Skills (OSATS), mini-clinical evaluation exercise (Mini-CEX) or case-based discussion (CBD). To measure progress in this PAG post-specialty training curriculum, the subspecialty trainee will be required to maintain and update a portfolio of experience and competency. (C) 2020

摘要： Background Although solely topical treatment often suffices, patients with psoriasis may require more intensive treatment (phototherapy and/or systemic treatments) to control their disease. However, in paediatric, adolescent and young adult patients, little is known about persistence of topical treatment and time until switch to systemic treatment. Objectives To determine the median time from psoriasis onset until (i) discontinuation of solely topical agents and (ii) switch to systemic treatment, and to identify patient characteristics associated with switching to systemic treatments. Methods Data were extracted from the Child-CAPTURE registry, a prospective, observational cohort of patients with paediatric-onset psoriasis followed into young adulthood from 2008 to 2018. Data prior to inclusion in the registry were collected retrospectively. Median times were determined through Kaplan-Meier survival analyses. Cox regression analysis was used to identify patient characteristics associated with switch to systemic treatment. Results Of 448 patients, 62 center dot 3% stayed on solely topical treatment until data lock;14 center dot 3% switched from topicals to phototherapy, but not to systemic treatment;and 23 center dot 4% switched to systemic treatment. The median time from psoriasis onset until discontinuation of solely topical treatment was 7 center dot 3 years, and until switch to systemics was 10 center dot 8 years. Higher Psoriasis Area and Severity Index and (Children's) Dermatology Life Quality Index > 5 were independently associated with switching to systemic treatment. Conclusions In a population of paediatric and adolescent patients with mild-to-severe psoriasis, one-third needed more intensive treatment than solely topical therapy to control their disease. We consider the median time until switching to systemics to be long.

关键词： Menetrier disease   Cytomegalovirus infection   Protein-losing gastropathy   Hypertrophic gastric folds   Inclusion bodies  

摘要： Paediatric Menetrier disease (PMD) is a protein-losing gastropathy, presenting with generalized oedema and abdominal symptoms. PMD commonly has an acute course and may be associated with Cytomegalovirus (CMV) infection. The aim of this retrospective study is to assess the epidemiological and clinical data, diagnostic procedures, treatment and outcome of CMV-associated PMD. The medical charts of the patients with PMD and CMV infection diagnosed at our hospital have been reviewed. Then, a systematic literature's review of all the cases of PMD and a selection of those associated with CMV infection have been performed. Three previously healthy boys were admitted for vomiting and oedema. Endoscopy showed hypertrophic gastric folds and CMV infection was diagnosed. Albumin was administered in all cases, with clinical resolution within few weeks. In literature, PMD has been described in 150 children and the association between CMV and PMD was found in 89 cases. Clinical and laboratory data, radiological and histological exams, therapy and outcome were reviewed. Conclusions: Basing on the present experience and on the current knowledge, PMD has a benign course without long-term sequelae. Although PMD is rare in children, we recommend paediatricians to consider CMV-related PMD when facing children with vomiting and diffuse oedema.

关键词： clonidine   critical care   paediatrics   sedation  

摘要： Aim: Although not approved, the alpha-adrenoceptor agonist clonidine is considered an option for long-term sedation protocols in paediatric intensive care. We reviewed adverse effects of clonidine occurring in this indication. Methods: Relevant literature was systematically identified from PubMed and Embase. We included interventional and observational studies on paediatric patients admitted to intensive care units and systemically long-term sedated with clonidine-containing regimes. In duplicates, we conducted standardised and independent full-text assessment and extraction of safety data. Results: Data from 11 studies with 909 patients were analysed. The studies were heterogeneous regarding patient characteristics (age groups, comorbidity, or comedication) and sedation regimes (dosage, route, duration, or concomitant sedatives). Just four randomised controlled trials (RCTs) and one observational study had comparison groups, using placebo or midazolam. For safety outcomes, our validity evaluation showed low risk of bias only in three studies. All studies focused on haemodynamic problems, particularly bradycardia and hypotension. Observed incidences or subsequent interventions never caused concerns. However, only two RCTs allowed meaningful comparisons with control groups. Odds ratios showed no significant difference between the groups, but small sample sizes (50 and 125 patients) must be considered;pooled analyses were not reasonable. Conclusion: All evaluated studies concluded that the use of clonidine in paediatric intensive care units is safe. However, a valid characterisation of the safety profile remains challenging due to limited, biased and heterogeneous data and missing investigation of long-term effects. This evaluation demonstrates the lack of data, which prevents reliable conclusions on the safety of clonidine for long-term sedation in critically ill children. For an evidence-based use, further studies are needed.

关键词： fine needle aspiration cytology   paediatric salivary gland   sialadenitis  

摘要： Fine needle aspiration cytology (FNAC) is generally characterized by a high diagnostic accuracy in differentiating non-neoplastic/inflammatory lesions from neoplastic lesions of the salivary glands. Lymphoepithelial sialadenitis/myoepithelial sialadenitis is exceedingly rare in paediatric patients and is characterized by a diffuse, often bilateral, salivary gland enlargement and the differential diagnosis may sometimes be difficult. We report the case of a 10-year-old boy who presented with a swelling of the left parotid gland investigated by ultrasound salivary gland FNAC.

关键词： Paediatric oncology   Epigenetic mechanisms   BET inhibitors   Paediatric Strategy Forum   Drug development   Cancer therapeutics   MYC/MYCN   NUT   Bromodomain  

摘要： Based on biology and pre-clinical data, bromodomain and extra-terminal (BET) inhibitors have at least three potential roles in paediatric malignancies: NUT (nuclear protein in testis) carcinomas, MYCIMYCN-driven cancers and fusion-driven malignancies. However, there are now at least 10 BET inhibitors in development, with a limited relevant paediatric population in which to evaluate these medicinal products. Therefore, a meeting was convened with the specific aim to develop a consensus among relevant biopharmaceutical companies, academic researchers, as well as patient and family advocates, about the development of BET inhibitors, including prioritisation and their specific roles in children. Although BET inhibitors have been in clinical trials in adults since 2012, the first-in-child study (BMS-986158) only opened in 2019. In the future, when there is strong mechanistic rationale or pre-clinical activity of a class of medicinal product in paediatrics, early clinical evaluation with embedded correlative studies of a member of the class should be prioritised and rapidly executed in paediatric populations. There is a strong mechanistic and biological rationale to evaluate BET inhibitors in paediatrics, underpinned by substantial, but not universal, pre-clinical data. However, most panBET inhibitors have been challenging to administer in adults, since monotherapy results in only modest anti-tumour activity and provides a narrow therapeutic index due to thrombocytopenia. It was concluded that it is neither scientifically justified nor feasible to undertake simultaneously early clinical trials in paediatrics of all pan-BET inhibitors. However, there is a clinical need for global access to BET inhibitors for patients with NUT carcinoma, a very rare malignancy driven by bromodomain fusions, with proof of concept of clinical benefit in a subset of patients treated with BET inhibitors. Development and regulatory pathway in this indication should include children and adolescen

关键词： narrowband UVB   paediatric   skintypes  

摘要： Background Narrowband ultraviolet B phototherapy (nbUVB) is a well-established, well-tolerated and efficacious treatment for eczema. There is a distinct lack of literature surrounding the therapeutic use of nbUVB in eczema in children and especially in children with higher skin phototypes (III to VI). Methods We undertook a retrospective review of children aged 18 years and under with eczema who had undergone nbUVB in our department between 1 January 2011 and 31 December 2017. ed data included sex, age, skin phototype, severity as graded by a paediatric dermatologist, cumulative dose, response to treatment and subsequent remission. Results In total, 60 children had nbUVB. Of those, 56 had more than 10 nbUVB exposures. Complete or near-complete clearance was achieved in 31 children (52%). Of those, 24 (77%) had a skin phototype of III or greater. Clinical remission rates of these patients were 100%, 87%, 57% and 52% at 0, 3, 6 and 12 months, respectively. Seventeen patients (28%) suffered side effects. Most commonly these were mild side effects such as erythema and xerosis. Conclusion We have demonstrated that nbUVB is a safe, well-tolerated and efficacious form of treatment for children with atopic eczema. We have shown it to be effective in those with skin phototypes greater than III and shown that they are a group that may derive greater long-term efficacy. In clinical practice, preference for nbUVB as second-line treatment, over oral systemics, should always be considered.