Diagnosis of foreign body aspiration with ultralow-dose CT using a tin filter: a comparison study.

PURPOSE: Suspected airway foreign body aspiration (FBA) is a common event in paediatric emergency units, especially in children under 3 years of age. It can be a life-threatening event if not diagnosed promptly and accurately. The purpose of this study is to compare the diagnostic performance of an ultralow-dose CT (DLP of around 1 mGycm) with that of conventional radiographic methods (fluoroscopy and chest radiography of the airways) in the diagnosis of FBA children's airways. METHODS: Retrospective cross-sectional study. Data from 136 children were collected: 75 were examined with conventional radiographic methods and 61 with ultralow-dose CT. Effective doses were compared using independent t tests. The results of bronchoscopy, if performed, were used in creating contingency 2 × 2 tables to assess the diagnostic performance between modalities. An extra triple reading of all images was applied for this purpose. RESULTS: The effective doses used in the ultralow-dose CT examinations were lower compared with those in conventional methods (p < 0.001). The median dose for CT was 0.04 mSv compared with 0.1 mSv for conventional methods. Sensitivity and specificity were higher for ultralow-dose CT than those for conventional methods (100% and 98% versus 33% and 96%) as were the positive and negative predicted values (90% and 100% versus 60% and 91%). CONCLUSION: Ultralow-dose CT can be used as the imaging of choice in the diagnosis of airway FBA in emergency settings, thereby avoiding concerns about radiation doses and negative bronchoscopy outcomes.

Clinical response of the novel activating ALK-I1171T mutation in neuroblastoma to the ALK inhibitor ceritinib.

Tumors with anaplastic lymphoma kinase (ALK) fusion rearrangements, including non-small-cell lung cancer and anaplastic large cell lymphoma, are highly sensitive to ALK tyrosine kinase inhibitors (TKIs), underscoring the notion that such cancers are addicted to ALK activity. Although mutations in ALK are heavily implicated in childhood neuroblastoma, response to the ALK TKI crizotinib has been disappointing. Embryonal tumors in patients with DNA repair defects such as Fanconi anemia (FA) often have a poor prognosis, because of lack of therapeutic options. Here we report a child with underlying FA and ALK mutant high-risk neuroblastoma responding strongly to precision therapy with the ALK TKI ceritinib. Conventional chemotherapy treatment caused severe, life-threatening toxicity. Genomic analysis of the initial biopsy identified germline FANCA mutations as well as a novel ALK-I1171T variant. ALK-I1171T generates a potent gain-of-function mutant, as measured in PC12 cell neurite outgrowth and NIH3T3 transformation. Pharmacological inhibition profiling of ALK-I1171T in response to various ALK TKIs identified an 11-fold improved inhibition of ALK-I1171T with ceritinib when compared with crizotinib. Immunoaffinity-coupled LC-MS/MS phosphoproteomics analysis indicated a decrease in ALK signaling in response to ceritinib. Ceritinib was therefore selected for treatment in this child. Monotherapy with ceritinib was well tolerated and resulted in normalized catecholamine markers and tumor shrinkage. After 7.5 mo treatment, the residual primary tumor shrunk, was surgically removed, and exhibited hallmarks of differentiation together with reduced Ki67 levels. Clinical follow-up after 21 mo treatment revealed complete clinical remission including all metastatic sites. Therefore, ceritinib presents a viable therapeutic option for ALK-positive neuroblastoma.

Hemorrhagic pleural effusion secondary to an unusual type III hiatal hernia in a 4-year-old great dane.

An unusual case of combined axial and paraesophageal (type III) hiatal hernia (HH) in a 4-year-old Great Dane is reported. The main presenting complaint was dyspnea, and no history of trauma was present. A tentative diagnosis of HH with secondary pleural effusion was made based on clinical signs and radiographic findings. Exploratory celiotomy revealed herniation of the gastric cardia, fundus, and body through the esophageal hiatus and an adjacent, distinct defect in the diaphragm. Rupture of the short gastric vessels lead to the formation of a hemorrhagic pleural effusion that impaired ventilation. The esophageal hiatus was surgically reduced in size, and the second defect was closed with nonabsorbable sutures. Esophagopexy and tube gastropexy procedures were also performed. The dog was clinically normal 9 months postoperatively. This type of HH is not currently defined within the traditional classification system and to the authors' knowledge has not been previously reported.

Genetic dissection of quantitative trait loci specifying sedative/hypnotic sensitivity to ethanol: mapping with interval-specific congenic recombinant lines.

BACKGROUND: Linkage studies alone do not produce sufficient resolution to narrow the location of a quantitative trait locus (QTL) to a small-enough chromosomal region for gene identification. One solution to this problem is to use interval-specific congenic recombinant (ISCR) lines to narrow the chromosomal interval known to contain the QTL. In previous work, we mapped four QTLs for differential ethanol sensitivity in the inbred long-sleep (ILS) and inbred short-sleep (ISS) strains and generated reciprocal congenic strains in which each full QTL interval from ILS was bred onto the ISS background and vice versa. METHODS: ISCR lines were derived by identifying mice carrying recombination events in the congenic interval during backcrossing of the ISS.ILS.Lore congenics to ISS. Recombinant mice were backcrossed to ISS, and progeny carrying the ISCR chromosome were identified and tested to determine whether the ISCR region carried the donor Lore QTL. RESULTS: We developed multiple ISCR lines for each Lore QTL, in which the QTL interval was broken into a number of smaller intervals. For all four QTLs, we reduced the size of the interval, in one case to 3.7 cM. CONCLUSIONS: Use of ISCR lines can narrow each Lore candidate region to a few centimorgans. Such an interval size is conducive to brute-force approaches to identify candidate genes, entailing bioinformatics, gene expression, and DNA sequencing strategies.