Genetic association studies often examine features independently, potentially missing subpopulations with multiple phenotypes that share a single cause. We describe an approach that aggregates phenotypes on the basis of patterns described by Mendelian diseases. We mapped the clinical features of 1204 Mendelian diseases into phenotypes captured from the electronic health record (EHR) and summarized this evidence as phenotype risk scores (PheRSs). In an initial validation, PheRS distinguished cases and controls of five Mendelian diseases. Applying PheRS to 21,701 genotyped individuals uncovered 18 associations between rare variants and phenotypes consistent with Mendelian diseases. In 16 patients, the rare genetic variants were associated with severe outcomes such as organ transplants. PheRS can augment rare-variant interpretation and may identify subsets of patients with distinct genetic causes for common diseases.

Summary.  Background: Central venous catheters (CVCs) are often inserted into boys with hemophilia to secure venous access for factor prophylaxis and immune tolerance induction therapy. Complications associated with CVCs include catheter‐related infections, local hemorrhage, and mechanical failure. Less frequently reported is CVC‐related deep venous thrombosis (DVT). We conducted a prospective study to determine the frequency and outcome of this complication. Methods: All boys (n = 16) with congenital hemophilia A or B with a CVC in place who were registered in the pediatric comprehensive care program at the Hospital for Sick Children, Toronto, were included in the study. They were prospectively assessed by imaging studies and clinical examinations for CVC‐related DVT at two time‐points, 2 years apart. Each boy was evaluated for inherited hypercoagulability. Results: Eleven (69%) of the 16 boys had radiological evidence of DVT at the first evaluation and 13/16 (81%) at the second evaluation. In two boys there was improvement in the venogram findings at the second evaluation. None of the CVC‐related DVTs completely resolved. Median age at the time of initial insertion of a CVC was 1.0 years (range 0.02–6.7 years). Median duration of CVC placement was 6.4 years (range 3.3–15.5 years). Only 4/13 boys with DVTs had clinical evidence of upper venous system obstruction. Only one boy, who did not develop a DVT, had a low protein C level. Conclusions: CVC‐related DVTs occur in the majority of boys with hemophilia who have CVCs inserted for a prolonged period of time. Annual screening with imaging is recommended for boys with CVCs in place for ≥ 3 years. Consideration should be given to removing CVCs as soon as peripheral venous access is feasible.

Sonographically guided percutaneous liver biopsy in infants is a good and effective diagnostic tool. The complication rate, however, even when performed by an experienced physician, is not insignificant in this age group of patients.

The lymphatic system, an important component of the circulatory system with essential physiologic functions, can be affected by various disease processes. There has been a delay in the development of effective imaging methods for the lymphatic system due to its small size, which limits visualization as well as introduction of contrast material. Traditionally, the lymphatic system has been imaged by injecting contrast material or radiotracers into the feet or hands. This is not sufficient for assessment of the central conducting lymphatics (CCLs) (such as the thoracic duct or the cisterna chyli). Fluoroscopic intranodal lymphangiography with injection of oil-based contrast material into groin lymph nodes improves visualization of CCLs but is limited in practice owing to the use of radiation and the potential risk for paradoxical embolization in children with left-to-right shunt. Dynamic contrast material-enhanced (DCE) magnetic resonance (MR) lymphangiography, which is performed by injecting gadolinium-based contrast material into groin lymph nodes, overcomes these limitations. T2-weighted imaging plays a complementary role to DCE MR lymphangiography in the assessment of CCLs. DCE MR lymphangiography demonstrates preserved integrity or any abnormality of the CCLs (including blockage or leak). The technique has recently been used in evaluating pulmonary lymphatic perfusion syndrome in children with plastic bronchitis, neonatal lymphatic flow disorders, and nontraumatic chylothorax. It is useful in identification of the source of chylous ascites and contributes to understanding of the anatomy of lymphatic malformations. It is successfully used for planning of embolization of aberrant lymphatic channels in a variety of lymphatic flow disorders. This review discusses the anatomy and function of the lymphatic system, the evolution of imaging of the lymphatic system, and DCE MR lymphangiography technique and its applications in children. RSNA, 2017.

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Arm position is the significant variable influencing PICC movement. Side, site and vein do not influence the range of movement significantly. Most PICCs descend deeper into the chest with arm adduction and elbow bending.

ABSTRACT. Objective. The management of parapneumonic effusions in children is controversial. The objective of this study was to evaluate the effectiveness and safety of intrapleural tissue plasminogen activator (tPA) in children who require tube thoracostomy for drainage of a complicated parapneumonic effusion.Methods. An observational cohort study was used to compare children who were treated with intrapleural tPA (either early or late administration) with children who were treated with thoracostomy tube drainage alone.Results. Over a 6-year period, 12 children received early tPA (within 24 hours of diagnosis), 18 children received late tPA (>24 hours after diagnosis), and 23 children received thoracostomy tube drainage alone for the management of a complicated parapneumonic effusion. Total pleural fluid drainage was highest for the late tPA group (691 mL vs 360 mL in the control group); however, the rate of pleural fluid drainage was highest for the early tPA group (7 mL/h vs 3 mL/h in the control group). The duration of chest tube placement was 84 hours for the early tPA group, 209 hours for the late tPA group, and 130 hours for the control group. There was a significant difference in duration of chest tube placement between the early and late tPA groups. No child who was treated with tPA developed local or systemic bleeding.Conclusions. Early administration of intrapleural tPA seems to be a safe and potentially effective treatment in children with complicated parapneumonic effusions. Randomized controlled trial evidence is needed to confirm this finding. Pediatrics 2004;113:e182-e185. URL: http://www.pediatrics.org/cgi/content/full/113/3/e182; alteplase, intrapleural fibrinolytics, parapneumonic effusion, tissue plasminogen activator.

Ultrasonographically guided botulinum toxin A injections into the salivary glands are safe and efficacious in the management of sialorrhea in children with neurologic disorders.