No abstract

IMPORTANCE Less than 10% of patients with cancer have detectable pathogenic germline alterations, which may be partially due to incomplete pathogenic variant detection.OBJECTIVE To evaluate if deep learning approaches identify more germline pathogenic variants in patients with cancer. DESIGN, SETTING, AND PARTICIPANTSA cross-sectional study of a standard germline detection method and a deep learning method in 2 convenience cohorts with prostate cancer and melanoma enrolled in the US and Europe between 2010 and 2017. The final date of clinical data collection was December 2017.EXPOSURES Germline variant detection using standard or deep learning methods. MAIN OUTCOMES AND MEASURESThe primary outcomes included pathogenic variant detection performance in 118 cancer-predisposition genes estimated as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The secondary outcomes were pathogenic variant detection performance in 59 genes deemed actionable by the American College of Medical Genetics and Genomics (ACMG) and 5197 clinically relevant mendelian genes. True sensitivity and true specificity could not be calculated due to lack of a criterion reference standard, but were estimated as the proportion of true-positive variants and true-negative variants, respectively, identified by each method in a reference variant set that consisted of all variants judged to be valid from either approach. RESULTSThe prostate cancer cohort included 1072 men (mean [SD] age at diagnosis, 63.7 [7.9] years; 857 [79.9%] with European ancestry) and the melanoma cohort included 1295 patients (mean [SD] age at diagnosis, 59.8 [15.6] years; 488 [37.7%] women; 1060 [81.9%] with European ancestry). The deep learning method identified more patients with pathogenic variants in cancer-predisposition genes than the standard method

No abstract

This study reports the clinical features and neuroimaging correlates of stroke in Saudi children seen over a 5-year period at the King Fahd Hospital of the University, Al-Khobar, Saudi Arabia. During the study period, 31 (18 boys, 13 girls; mean age, 26.2 months) of the 20,895 children seen had stroke; the annual stroke incidence was 29.7 per 100,000 in the pediatric population. Ischemic strokes accounted for 90% and hemorrhagic 10% of the cases, respectively. The boys-to-girls ratio for ischemic stroke was 2:1. Cranial computed tomographic scans and magnetic resonance imaging findings were abnormal in 82% and 91%, respectively. The etiologic factor was undetermined in 65% of the cases. Our results suggest that stroke is uncommon in Saudi children. However, further studies evaluating a larger population in different clinical settings are required to provide a more comprehensive picture of stroke in children in this area.

The clinical patterns, including history, examination, and electroencephalographic (EEG) and computed tomography (CT) findings were examined prospectively in 263 children (153 boys, 110 girls) with newly diagnosed recurrent seizures. The overall mean age was 4. 2 years, with a range of 0.05-13 years. The age of onset was within the first year of life in 128 (48.7%) of the patients. Hypoxic-ischemic encephalopathy (14.8%), febrile seizures (9.1%) and developmental delay (4.6%) were the predominant signs in this age group. Consanguinity of the parents was present in 29.7% cases. The main EEG abnormalities were epileptiform activity, which was generalized in 133 (50.6%) and focal in 80 (30.4%). Other abnormalities included slow wave activity in 41 (15.6%) and hypsarrhythmia in 3 (1.1%). The main seizure types were generalized in 60.4% and partial in 32.7%. The types of epileptic syndromes included localization-related (28.1%), generalized (23.2%), undetermined (37.4%) and (special) syndromes 11.4%. The cranial CT findings were normal in 60.5%, and the predominant abnormality was cerebral atrophy in 25.3%. The pattern of seizure types and the peak presentation in early childhood are comparable to those in western reports.

No abstract

No abstract

Phase I study of bortezomib combined with chemotherapy in children with relapsed childhood acute lymphoblastic leukemia (ALL): a report from the therapeutic advances in childhood leukemia (TACL) consortium.