Heterogeneous Liver on Research Ultrasound Identifies Children with Cystic Fibrosis at High Risk of Advanced Liver Disease: Interim Results of a Prospective Observational Case-Controlled Study.

OBJECTIVE: To assess if a heterogeneous pattern on research liver ultrasound examination can identify children at risk for advanced cystic fibrosis (CF) liver disease. STUDY DESIGN: Planned 4-year interim analysis of a 9-year multicenter, case-controlled cohort study (Prospective Study of Ultrasound to Predict Hepatic Cirrhosis in CF). Children with pancreatic insufficient CF aged 3-12 years without known cirrhosis, Burkholderia species infection, or short bowel syndrome underwent a screening research ultrasound examination. Participants with a heterogeneous liver ultrasound pattern were matched (by age, Pseudomonas infection status, and center) 1:2 with participants with a normal pattern. Clinical status and laboratory data were obtained annually and research ultrasound examinations biannually. The primary end point was the development of a nodular research ultrasound pattern, a surrogate for advanced CF liver disease. RESULTS: There were 722 participants who underwent screening research ultrasound examination, of which 65 were heterogeneous liver ultrasound pattern and 592 normal liver ultrasound pattern. The final cohort included 55 participants with a heterogeneous liver ultrasound pattern and 116 participants with a normal liver ultrasound pattern. All participants with at least 1 follow-up research ultrasound were included. There were no differences in age or sex between groups at entry. Alanine aminotransferase (42 ± 22 U/L vs 32 ± 19 U/L; P = .0033), gamma glutamyl transpeptidase (36 ± 34 U/L vs 15 ± 8 U/L; P < .001), and aspartate aminotransferase to platelet ratio index (0.7 ± 0.5 vs 0.4 ± 0.2; P < .0001) were higher in participants with a heterogeneous liver ultrasound pattern compared with participants with a normal liver ultrasound pattern. Participants with a heterogeneous liver ultrasound pattern had a 9.1-fold increased incidence (95% CI, 2.7-30.8; P = .0004) of nodular pattern vs a normal liver ultrasound pattern (23% in heterogeneous liver ultrasound pattern vs 2.6% in normal liver ultrasound pattern). CONCLUSIONS: Research liver ultrasound examinations can identify children with CF at increased risk for developing advanced CF liver disease.

The international diffuse intrinsic pontine glioma registry: an infrastructure to accelerate collaborative research for an orphan disease.

Diffuse intrinsic pontine glioma (DIPG), a rare, often fatal childhood brain tumor, remains a major therapeutic challenge. In 2012, investigators, funded by the DIPG Collaborative (a philanthropic partnership among 29 private foundations), launched the International DIPG Registry (IDIPGR) to advance understanding of DIPG. Comprised of comprehensive deidentified but linked clinical, imaging, histopathological, and genomic repositories, the IDIPGR uses standardized case report forms for uniform data collection; serial imaging and histopathology are centrally reviewed by IDIPGR neuro-radiologists and neuro-pathologists, respectively. Tissue and genomic data, and cell cultures derived from autopsies coordinated by the IDIPGR are available to investigators for studies approved by the Scientific Advisory Committee. From April 2012 to December 2016, 670 patients diagnosed with DIPG have been enrolled from 55 participating institutions in the US, Canada, Australia and New Zealand. The radiology repository contains 3558 studies from 448 patients. The pathology repository contains tissue on 81 patients with another 98 samples available for submission. Fresh DIPG tissue from seven autopsies has been sent to investigators to develop primary cell cultures. The bioinformatics repository contains next-generation sequencing data on 66 tumors. Nine projects using data/tissue from the IDIPGR by 13 principle investigators from around the world are now underway. The IDIPGR, a successful alliance among philanthropic agencies and investigators, has developed and maintained a highly collaborative, hypothesis-driven research infrastructure for interdisciplinary and translational projects in DIPG to improve diagnosis, response assessment, treatment and outcome for patients.

Improving consistency in radiology reporting through the use of department-wide standardized structured reporting.

PURPOSE: To successfully develop a department-wide standardized structured reporting program and achieve widespread adoption throughout the radiology department. MATERIALS AND METHODS: A structured reporting work group was formed in February 2010 to oversee development of standardized structured reports for a radiology department of 36 radiologists at a tertiary care children's hospital. The committee reached consensus on report organization and provided written guidelines and checklists for division representatives to aid in creation of the structured reports. Report drafts were reviewed by a subcommittee and revised until agreement was reached with the report author. Each report was vetted by all radiologists who would be using the report, and further revisions were made, as appropriate. Reports were then entered into the speech recognition system so that each report was associated with a procedure code or a group of codes from the radiology information system. This enabled automatic report population within the speech recognition system. The initiative was completed by September 2011. Quarterly audits were performed to evaluate for adherence to the standard report format and use of the normal report in cases in which the radiologist believed the study was normal. In August 2012, radiologists were surveyed as to their impressions of the structured reporting program. RESULTS: A total of 228 standardized structured reports were created within 2 years after initiation of the project, corresponding to 199,000 (94%) of 212,000 departmental studies by volume. By the end of the implementation period in September 2011, all 223 (100%) audited reports adhered to the standard report format and 80 (99%) of 81 reports adhered to the normal report. Radiologist feedback was largely favorable. CONCLUSION: Standardized department-wide structured reporting can be implemented in a radiology department, with a high rate of adoption by the radiologists.

Heterogeneous liver on research ultrasound identifies children with cystic fibrosis at high risk of advanced liver disease.

BACKGROUND: This study examines whether heterogeneous (HTG) pattern on liver ultrasound (US) identifies children at risk for advanced cystic fibrosis liver disease (aCFLD). METHODS: Prospective 6-year multicenter case-controlled cohort study. Children with pancreatic insufficient cystic fibrosis (CF) aged 3-12 years without known cirrhosis underwent screening US. Participants with HTG were matched (by age, Pseudomonas infection status and center) 1:2 with participants with normal (NL) US pattern. Clinical status and laboratory data were obtained annually and US bi-annually for 6 years. Primary endpoint was development of nodular (NOD) US pattern consistent with aCFLD. RESULTS: 722 participants underwent screening US, with 65 HTG and 592 NL. Final cohort included 55 HTG and 116 NL with ≥ 1 follow-up US. ALT, AST, GGTP, FIB-4, GPR and APRI were higher, and platelets were lower in HTG compared to NL. HTG had a 9.5-fold increased incidence (95% confidence interval [CI]:3.4, 26.7, p<0.0001, 32.7% vs 3.4%) of NOD versus NL. HTG had a sensitivity of 82% and specificity of 75% for subsequent NOD. Negative predictive value of a NL US for subsequent NOD was 96%. Multivariate logistic prediction model that included baseline US, age, and log(GPR) improved the C-index to 0.90 compared to only baseline US (C-index 0.78). Based on survival analysis, 50% of HTG develop NOD after 8 years. CONCLUSIONS: Research US finding of HTG identifies children with CF with a 30-50% risk for aCFLD. A score based on US pattern, age and GPR may refine the identification of individuals at high risk for aCFLD. CLINICAL TRIAL REGISTRATION: Prospective Study of Ultrasound to Predict Hepatic Cirrhosis in CF: NCT 01,144,507 (observational study, no consort checklist).

Risk Stratification to Decrease Unnecessary Diagnostic Imaging for Acute Appendicitis.

BACKGROUND: There has been an increase in the use of imaging modalities to diagnose appendicitis despite evidence that can help identify children at especially high or low risk of appendicitis who may not benefit. We hypothesized that the passive diffusion of a standardized care pathway (including diagnostic imaging recommendations) would improve the diagnostic workup of appendicitis by safely decreasing the use of unnecessary imaging when compared with historical controls and that an electronic, real-time decision support tool would decrease unnecessary imaging. METHODS: We used an interrupted time series trial to compare proportions of patients who underwent diagnostic imaging (computed tomography [CT] and ultrasound) between 3 time periods: baseline historical controls, after passive diffusion of a diagnostic workup clinical pathway, and after introduction of an electronic medical record-embedded clinical decision support tool that provides point-of-care imaging recommendations (active intervention). RESULTS: The moderate- and high-risk groups showed lower proportions of CT in the passive and active intervention time periods compared with the historical control group. Proportions of patients undergoing ultrasound in all 3 risk groups showed an increase from the historical baseline. Time series analysis confirmed that time trends within any individual time period were not significant; thus, incidental secular trends over time did not appear to explain the decreased use of CT. CONCLUSIONS: Passive and active decision support tools minimized unnecessary CT imaging; long-term effects remain an important area of study.

Ultrasound diagnosis of craniosynostosis.

OBJECTIVE: To retrospectively study prenatal ultrasound images of patients with craniosynostosis to determine the extent to which prenatal diagnosis is possible. METHOD: Prenatal ultrasound images of 19 patients with postnatally diagnosed metopic or coronal suture craniosynostosis were retrospectively reviewed. The 26 ultrasound examinations obtained were compared with normal images and tables of gestation. RESULTS: It was not possible to diagnose craniosynostosis in the first trimester. In the second trimester, Kleeblattschädel was diagnosed at 20.5 weeks. A multilobular shape to the skull and diastasis of the frontotemporal suture was identified. In a second child with Kleeblattschädel, the cephalic index was above normal 86.4 (normal range 70 to 86), and the head circumference to abdominal circumference was increased. In the third trimester, the head shape deformation was more obvious. Brachycephaly diagnosis was made in the second trimester. In Crouzon syndrome the hypertelorism was identified at 19.9 weeks. Plagiocephaly was diagnosed at 21.4 weeks. In trigonocephaly the reduced cephalic index was noted at 18.8 weeks. In the third trimester, the deformity was diagnosed in all cases. CONCLUSION: No diagnosis of craniosynostosis was made in the first trimester. In the second trimester, it was possible to diagnose Kleeblattschädel, trigonocephaly, brachycephaly (bilateral coronal suture craniosynostosis), and plagiocephaly (unilateral coronal suture craniosynostosis) in nine of the examinations. In the third trimester and at term, it was possible to diagnose previously listed conditions from six of the seven examinations obtained. Kleeblattschädel was suspected during original examination. A total of 15 examinations of 26 were correctly diagnosed during this investigation.