三谷 忠宏

OBJECTIVE: To evaluate the efficacy and safety of Tumguide®, a radiation-free, transillumination-guided system for gastric tube (GT) placement in neonates. STUDY DESIGN: This single-center prospective observational study enrolled neonates requiring GT placement. Tumguide® was used to guide placement. Primary outcomes were intragastric placement success rate and accuracy, defined as radiographically confirmed positioning not requiring adjustment. RESULTS: A total of 71 procedures were performed in 55 neonates. Median gestational age was 37.1 weeks, and median birth weight was 2480 g. The overall intragastric placement success rate was 99%, with 73% accuracy. No adverse events were reported. Protocol modifications significantly improved accuracy from 17% to 85% (p < 0.001). Tumguide® maintained high accuracy across varying body weights. CONCLUSIONS: Tumguide® enables accurate and successful GT placement in neonates. Its real-time visualization and compatibility with small-caliber tubes support its utility as a practical alternative to traditional methods. CLINICAL TRIAL REGISTRATION (IF ANY): This study was registered in the University Hospital Medical Information Network Clinical Trials Registry in Japan (ID: UMIN000055947, URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000063917 ).

Nardilysin (NRDC) plays a role in multiple cellular functions in diverse cellular compartments, including ectodomain shedding in the plasma membrane, as well as chaperoning a key Krebs cycle enzyme in mitochondria. We had previously reported limited clinical information from two individuals with homozygous frameshift variants in NRDC. With inclusion of previously published individuals, here we report 14 individuals (10 females, four males) from nine unrelated families carrying homozygous NRDC pathogenic variants. Common clinical features include severe to profound developmental delay/intellectual disability (12/12), microcephaly (13/13), prematurity (5/13), lethality in the first 3 years of life (9/14), seizures (7/11), joint contractures (4/8), eye/visual abnormalities (5/7), and abnormal brain imaging studies ranging from diffuse atrophy to lissencephaly (8/11). The identified variants include two splice, three frameshift, and three missense variants. RT-PCR from affected individual fibroblasts and a minigene assay in HEK293T cells demonstrate that the splice variants led to exon skipping of NRDC. To further investigate the pathogenicity of the variants in vivo, we used the Drosophila Nrdc (dNrdc) mutant model. dNrdc null mutants caused developmental lethality, which is fully rescued by wild-type human NRDC. Studies in the Drosophila dNrdc mutant models showed that both splice variants and frameshift variants cause severe loss of function, leading to lethality, whereas missense variants cause partial lethality and short lifespan, consistent with less severe phenotype. Our data establish that homozygous variants in NRDC are pathogenic, leading to highly lethal and severe neurodevelopmental disorder in humans.

INTRODUCTION: Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare disorder caused by antibodies against platelet factor 4 (PF4) triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines using non-replicable adenoviral vectors. It emerged during the pandemic, with patients typically presenting with thrombosis at uncommon sites, thrombocytopenia, and elevated D-dimer levels. VITT antibodies and heparin-dependent antibodies bind to distinct PF4 epitopes. Recently, VITT-like clinical, laboratory, and anti-PF4 antibody features have also been observed in patients with adenoviral infections. Only four pediatric cases of cerebral venous sinus thrombosis (CVST) have been reported. CASE REPORT: The patient was a previously healthy 2-year-old girl with no history of heparin exposure or SARS-CoV-2 vaccination. She presented with fever and was diagnosed with adenovirus infection. The fever resolved by day 4, but by day 6 she became increasingly lethargic and experienced vomiting. On day 12, Laboratory data showed severe thrombocytopenia and elevated D-dimer levels. Computed tomography revealed CVST along with a secondary hemorrhage in the right temporal lobe. She underwent hematoma removal with external/internal decompression and was started on continuous intravenous unfractionated heparin, and she was switched to warfarin. The thrombus decreased, platelet count spontaneously increased. Platelet activation assays using acute-phase serum identified a PF4-dependent platelet-activating antibody. CONCLUSION: We report a case of CVST in a 2-year-old girl following adenovirus infection. Unlike heparin-induced thrombocytopenia, where heparin exacerbates the condition, it is effective here by competitively inhibiting anti-PF4 antibody binding. In patients with prior adenovirus infection presenting with CVST and thrombocytopenia, anti-PF4 disorders should be considered.

Rare diseases are collectively common, affecting approximately 1 in 20 individuals worldwide. In recent years, rapid progress has been made in rare disease diagnostics due to advances in next-generation sequencing, development of new computational and functional genomics approaches to prioritize genes and variants and increased global sharing of clinical and genetic data. However, more than half of individuals suspected to have a rare disease lack a genetic diagnosis. The Genomics Research to Elucidate the Genetics of Rare Diseases (GREGoR) Consortium was initiated to study thousands of challenging rare disease cases and families and apply, standardize and evaluate emerging genomics technologies and analytics to accelerate their adoption in clinical practice. Furthermore, all data generated, currently representing over 7,500 individuals from over 3,000 families, are rapidly made available to researchers worldwide through the Analysis, Visualization and Informatics Lab-space (AnVIL) to catalyse global efforts to develop approaches for genetic diagnoses in rare diseases. Most of these families have undergone previous clinical genetic testing but remained unsolved, with most being exome-negative. Here we describe the collaborative research framework, datasets and discoveries comprising GREGoR that will provide foundational resources and substrates for the future of rare disease genomics.

We report a rare case of pediatric supraclavicular pyogenic lymphadenitis presenting with an "asymmetrical shoulder" in a five-year-old boy. The boy developed right neck and shoulder pain following the resolution of cellulitis at the site of insect bites on his right forearm. Despite the absence of visible inflammation in the shoulder or proximal lymph nodes, short tau inversion recovery magnetic resonance imaging (STIR-MRI) revealed an enlarged supraclavicular lymph node with surrounding edema. He fully recovered following intravenous antibiotic treatment. This case highlights that lymphadenitis in remote drainage sites, such as the supraclavicular nodes, may develop even after the resolution of distal cellulitis at the primary site. Notably, in the present case, inflammation was absent in the anatomically proximal lymph nodes (such as those at the elbow or subclavicular lymph nodes) and appeared only in the supraclavicular region. Lastly, the asymmetrical shoulder appearance may serve as a valuable clinical sign of the underlying lymphadenitis. We also discuss key considerations when encountering supraclavicular lymphadenitis, which carries a high risk of malignancy at all ages.