Objective

H epatocellular carcinoma (HCC) is the fifth most common human cancer and third most frequent cause of cancer death worldwide. 1 Although over 80% of new HCC cases will occur in Eastern Asia and subSaharan Africa, 2 the startling increase in HCC incidence in the United States over the past 20-25 years and the typically high mortality from this disease have established HCC as an important health concern in this country. [2][3][4][5][6] The clinical management of HCC is complicated by typically late-stage disease at presentation and prevalent underlying liver dysfunction that can render patients ineligible for potentially curative surgical therapies, which are generally suitable for only 20%-30% of HCC patients. 3,5,7 Although regional therapies, such as transarterial embolization and percutaneous treatments, are used in patients with nonresectable disease, their success is curtailed by recurrence as locally advanced or metastatic disease. For these patients, systemic therapy is indicated but has been largely unsuccessful. 3,4,[8][9][10] Thus, a clear need exists to develop effective, life-prolonging therapeutic strategies for the large number of HCC patients with advanced disease.A major challenge in the systemic treatment of HCC is cellular resistance to conventional cytotoxic agents, which, at

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Background and Purpose-There is little data regarding the cost of pediatric stroke care or the elements that contribute to these costs. We examined costs for poststroke care during the first year after diagnosis and compared these costs with the volume of the cerebral infarct and the level of neurological and functional outcome. Methods-We identified 39 children who sustained nontraumatic ischemic or hemorrhagic strokes and confirmed the diagnoses by review of medical and radiology records. Medical costs were tabulated for the year after the diagnosis of stroke. Cerebral infarct volumes were measured from MRI or CT scans. Neurological outcome was assessed by telephone with a modification of the Pediatric Stroke Outcome Measure (PSOM), and functional outcomes were assessed with a standardized quality-of-life measure. Results-The median cost for poststroke care during the year after diagnosis was $42 338 for the entire group. The cost for stroke care was higher for hemorrhagic stroke than for ischemic stroke. Cost had a significant positive correlation with neurological impairment. The modified PSOM score positively correlated with impairments of physical, emotional, social, and school function. Conclusions-The cost of stroke care may be one measure of stroke severity, with more extensive strokes resulting in greater medical costs. In addition, stroke appears to impair children's social ability along with their neurological function. (Stroke. 2008;39:161-165.)

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Researchers using EHR-based phenotype definitions should clearly specify the characteristics that comprise the definition, variations of ADA criteria, and how different phenotype definitions and components impact the patient populations retrieved and the intended application. Careful attention to phenotype definitions is critical if the promise of leveraging EHR data to improve individual and population health is to be fulfilled.

BackgroundWhole-exome sequencing (WES) has become an invaluable tool for genetic diagnosis in paediatrics. However, it has not been widely adopted in the prenatal setting. This study evaluated the use of WES in prenatal genetic diagnosis in fetuses with structural congenital anomalies (SCAs) detected on prenatal ultrasound.MethodThirty-three families with fetal SCAs on prenatal ultrasonography and normal chromosomal microarray results were recruited. Genomic DNA was extracted from various fetal samples including amniotic fluid, chorionic villi, and placental tissue. Parental DNA was extracted from peripheral blood when available. We used WES to sequence the coding regions of parental-fetal trios and to identify the causal variants based on the ultrasonographic features of the fetus.ResultsPathogenic mutations were identified in three families (n = 3/33, 9.1%), including mutations in DNAH11, RAF1 and CHD7, which were associated with primary ciliary dyskinesia, Noonan syndrome, and CHARGE syndrome, respectively. In addition, variants of unknown significance (VUSs) were detected in six families (18.2%), in which genetic changes only partly explained prenatal features.ConclusionWES identified pathogenic mutations in 9.1% of fetuses with SCAs and normal chromosomal microarray results. Databases for fetal genotype-phenotype correlations and standardized guidelines for variant interpretation in prenatal diagnosis need to be established to facilitate the use of WES for routine testing in prenatal diagnosis.Electronic supplementary materialThe online version of this article (10.1186/s12920-018-0409-z) contains supplementary material, which is available to authorized users.