Alder Hey Children's Hospital is a children's hospital and NHS foundation trust in West Derby, Liverpool, England. It is one of the largest children's hospitals in the United Kingdom, and one of several specialist hospitals within the Liverpool City Region, alongside the Royal Liverpool University Hospital, Liverpool Women's Hospital, Liverpool Heart and Chest Hospital, the Walton Centre, Mersey Regional Burns and Plastic Surgery Unit, and Clatterbridge Cancer Centre.
Young children are at increased risk for respiratory tract infections and are frequently colonized by respiratory pathogens. However, how the mucosal immune system differs between children and adults is relatively unknown. We collected nasal samples from 50 young children (aged 1-5 years) and 318 young adults (aged 18-34 years) to study how the mucosal immune system and host-microbe interactions differ with age. We used multi-omics data integration to combine host (immunophenotyping, transcriptomic, and cytokines) and microbial (16S-rRNA amplicon sequencing, viral PCRs, and pneumococcal culture) datasets. Young children had a paucity of mucosal granulocytes, while B and T cell subsets were increased. Children also had increased immune activation and inflammation, which associated with the presence of Haemophilus spp. and pneumococcus, but not viruses. In adults, Haemophilus spp. associated with T cell and monocyte recruitment, while Dolosigranulum negatively associated with neutrophil degranulation. Thus, nasal immune composition and host-pathogen interactions were clearly age dependent.
Abstract Spitz tumours are defined by molecular alterations, which include HRAS activating mutations, activating fusions of receptor tyrosine kinases (e.g. ROS1, ALK, NTRK3) and activating fusions of kinases (BRAF, RAF1, MAP3K8) (de la Fouchardière A, Tee MK, Peternel S et al. Fusion partners of NTRK3 affect subcellular localization of the fusion kinase and cytomorphology of melanocytes. Mod Pathol 2021; 34: 735–47). These mutations confer distinctive morphological features to the lesion, recognition of which can direct ancillary investigations and distinction from melanoma. In NTRK-driven tumours, the fusion partner can affect the subcellular localization of the fusion kinase and cytomorphology of the cell. We present a case of NTRK:MYO5A-fused Spitz naevus with characteristic spindled morphology and pseudo-Verocay bodies. A 9-year-old patient presented with a supraumbilical lesion that histologically comprised a dome-shaped dermal melanocytic proliferation with biphenotypic appearance and deep extension. It contained fascicles of spindled cells with ‘pseudo-Verocay bodies’ and superficial dermal nests containing banal naevus cells. Initial low-power impression of NTRK immunohistochemistry appeared negative; however, higher-power examination revealed weak, granular staining along dendritic processes. BRAF, ALK, ROS1 and PRAME were negative. Molecular analysis revealed presence of a MYO5A:NTRK3 fusion consistent with a MYO5A:NTRK3-fused Spitz naevus. A subset of NTRK3-fused tumours is diagnostically challenging as their Spitz classification may be missed due to absence of typical epithelioid morphology and glassy cytoplasm [Addo AK, Beydoun HM, Jeyakumar JE et al. Clinical, morphologic, and molecular findings in neurotrophic tyrosine receptor kinase 3 (NTRK3) fusion Spitz neoplasms. Mod Pathol 2025; 38:100888]. MYO5A:NTRK3-fused Spitz naevi in particular present with spindled melanocytes, fascicular architecture and nuclear palisading resembling Verocay bodies, raising differential diagnoses of soft-tissue neoplasms. MYO5A:NTRK3-fused Spitz naevi show a linear pattern of NTRK immunohistochemistry due to localization of the MYO5A:NTRK3 fusion protein within dendritic processes. This feature may be disregarded on low-power examination and poses a risk of false negative interpretation. Five morphological patterns of NRTK3-driven Spitz tumours are documented, which range from conventional Spitz to spindle cell variants. Recognizing the specific features of NTRK3:MYO5A-fused Spitz naevi facilitates accurate histological interpretation, prompting pathologists to request the relevant investigations and avoid misdiagnoses.
OBJECTIVE:To collate and systematically review the evidence on the impact of substandard housing on early child development in high-income countries. DESIGN:Systematic review. METHODS:Five databases (Medline, Emcare, Web of Science, Scopus and PsycInfo) and relevant grey literature were searched between June and July 2024. Records were screened to include studies which explored the association between substandard housing and cognitive, language, motor, social, emotional and/or behavioural development in children aged 0-8 years living in high-income countries. Studies which only explored lead, radiation or secondhand smoking exposures were excluded. Data were extracted from relevant articles and reported via a narrative synthesis. Risk of bias was assessed using the Risk of Bias in Non-Randomised Studies of Exposures tool. Certainty of findings was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. All screening, data extraction and 20% of quality assessment were performed independently by a second assessor. RESULTS:6258 records were screened, from which 25 studies were included, representing >2 29 000 children from seven high-income countries. Studies mostly explored home air quality and overcrowding. Moderate certainty evidence was found for associations between mould, damp, condensation, overcrowding, hygiene and safety issues and unclean heating/cooking fuels and poorer early child development. Low certainty evidence was found for an inverse relationship with nitrogen dioxide, particulate matter and xylene levels. Very low certainty evidence was found for associations between limited home resources and poorer child development. ORs ranged from 1.28 to 3.53. All studies had a high or very high risk of bias. Meta-analysis was not possible due to heterogeneity. CONCLUSIONS:Policymakers and professionals working with children in healthcare, social and education settings should be aware that housing conditions may impact child development. Research is needed to further evaluate the impacts of substandard housing on childhood development, but notwithstanding this, our review supports the growing momentum for improving living situations for young children. FUNDING:No specific funding was received for this study. PROTOCOL REGISTRATION:PROSPERO: CRD42024564320.
