A Predictive Model for Thiamine Responsive Disorders Among Infants and Young Children: Results from a Prospective Cohort Study in Lao People's Democratic Republic.

OBJECTIVE: To develop a predictive model for thiamine responsive disorders (TRDs) among infants and young children hospitalized with signs or symptoms suggestive of thiamine deficiency disorders (TDDs) based on response to therapeutic thiamine in a high-risk setting. STUDY DESIGN: Children aged 21 days to <18 months hospitalized with signs or symptoms suggestive of TDD in northern Lao People's Democratic Republic were treated with parenteral thiamine (100 mg daily) for ≥3 days in addition to routine care. Physical examinations and recovery assessments were conducted frequently for 72 hours after thiamine was initiated. Individual case reports were independently reviewed by three pediatricians who assigned a TRD status (TRD or non-TRD), which served as the dependent variable in logistic regression models to identify predictors of TRD. Model performance was quantified by empirical area under the receiver operating characteristic curve. RESULTS: A total of 449 children (median [Q1, Q3] 2.9 [1.7, 5.7] months old; 70.3% exclusively/predominantly breastfed) were enrolled; 60.8% had a TRD. Among 52 candidate variables, those most predictive of TRD were exclusive/predominant breastfeeding, hoarse voice/loss of voice, cyanosis, no eye contact, and no diarrhea in the previous 2 weeks. The area under the receiver operating characteristic curve (95% CI) was 0.82 (0.78, 0.86). CONCLUSIONS: In this study, the majority of children with signs or symptoms of TDD responded favorably to thiamine. While five specific features were predictive of TRD, the high prevalence of TRD suggests that thiamine should be administered to all infants and children presenting with any signs or symptoms consistent with TDD in similar high-risk settings. The usefulness of the predictive model in other contexts warrants further exploration and refinement. TRIAL REGISTRATION: Clinicaltrials.gov NCT03626337.

Can lung airway geometry be used to predict autism? A preliminary machine learning-based study.

The goal of this study is to assess the feasibility of airway geometry as a biomarker for autism spectrum disorder (ASD). Chest computed tomography images of children with a documented diagnosis of ASD as well as healthy controls were identified retrospectively. Fifty-four scans were obtained for analysis, including 31 ASD cases and 23 controls. A feature selection and classification procedure using principal component analysis and support vector machine achieved a peak cross validation accuracy of nearly 89% using a feature set of eight airway branching angles. Sensitivity was 94%, but specificity was only 78%. The results suggest a measurable difference in airway branching angles between children with ASD and the control population.

Update on the Role of Imaging in Staging of Common Pediatric Abdominal Tumors.

Neuroblastoma, Wilms tumor, and hepatoblastoma are the most common pediatric abdominal malignancies. Management of these diseases is a multidisciplinary process that continues to evolve based on the results of international collaborative trials and advances in understanding of tumor biology. Each of these tumors has unique characteristics and behavior which are reflected in their respective staging systems. It is important for clinicians involved in the care of children with abdominal malignancies to be familiar with current staging guidelines and imaging recommendations. This article reviews the current role of imaging in the management of these common pediatric abdominal malignancies, with emphasis on initial staging.

Establishing a case definition of thiamine responsive disorders among infants and young children in Lao PDR: protocol for a prospective cohort study.

INTRODUCTION: Diagnosis of infantile thiamine deficiency disorders (TDD) is challenging due to the non-specific, highly variable clinical presentation, often leading to misdiagnosis. Our primary objective is to develop a case definition for thiamine responsive disorders (TRD) to determine among hospitalised infants and young children, which clinical features and risk factors identify those who respond positively to thiamine administration. METHODS AND ANALYSIS: This prospective study will enrol 662 children (aged 21 days to <18 months) seeking treatment for TDD symptoms. Children will be treated with intravenous or intramuscular thiamine (100 mg daily for a minimum of 3 days) alongside other interventions deemed appropriate. Baseline assessments, prior to thiamine administration, include a physical examination, echocardiogram and venous blood draw for the determination of thiamine biomarkers. Follow-up assessments include physical examinations (after 4, 8, 12, 24, 36, 48 and 72 hours), echocardiogram (after 24 and 48 hours) and one cranial ultrasound. During the hospital stay, maternal blood and breast-milk samples and diet, health, anthropometric and socio-demographic information will be collected for mother-child pairs. Using these data, a panel of expert paediatricians will determine TRD status for use as the dependent variable in logistic regression models. Models identifying predictors of TRD will be developed and validated for various scenarios. Clinical prediction model performance will be quantified by empirical area under the receiver operating characteristic curve, using resampling cross validation. A frequency-matched community-based cohort of mother-child pairs (n=265) will serve as comparison group for evaluation of potential risk factors for TRD. ETHICS AND DISSEMINATION: Ethical approval has been obtained from The National Ethics Committee for Health Research, Ministry of Health, Lao PDR and the Institutional Review Board of the University of California Davis. The results will be disseminated via scientific articles, presentations and workshops with representatives of the Ministry of Health. TRIAL REGISTRATION NUMBER: NCT03626337.

Outcomes of Preoperative Versus Postoperative Radiation for Heterotopic Ossification Prevention in Children With Neuromuscular Hip Dysplasia Undergoing Proximal Femoral Resection.

BACKGROUND: Few studies exist to inform the extrapolated practice of irradiating children for heterotopic ossification (HO) prevention. We report the incidence of HO formation following prophylactic preoperative compared with postoperative radiation therapy (RT) in children with neuromuscular hip dysplasia (NHD) following proximal femoral resection (PFR). METHODS: A retrospective, 2-institution chart review was performed. Eligibility was limited to patients with at least 1 year of follow-up. Evaluation included radiographic HO grading by a combined severity scale, assessment of synchronous symptoms of pain or decreased range of motion, and stratification by preoperative versus postoperative reception of RT. A control cohort included 4 nonirradiated hips with NHD after PFR. RESULTS: Twenty-five hips in 20 children met eligibility criteria. Eleven hips were irradiated preoperatively and 14 postoperatively. Radiographic evidence of post-RT development of radiographic evidence of heterotopic ossification (rHO) was found in all 25 hips and earlier in patients irradiated preoperatively (median time to rHO was 4.0 vs. 15.7 mo, P=0.03, 95% confidence interval, 0.24-21.5). There was no statistically significant difference in the development of symptomatic HO (P=0.62) between the preoperative (45.5%) and postoperative (35.7%) groups, nor in HO grade (P=0.34). Seven (28%) of the 25 hips (5 preoperative and 2 postoperative) had documentation of rHO-free intervals after surgery, with an average duration of 5.6 months, while the remaining presented with rHO at first follow-up visit. All eligible control hips (100%) developed rHO and symptomatic heterotopic ossification. CONCLUSIONS: Perioperative RT did not prevent the formation of HO in any child with NHD after PFR. Extrapolation of evidence of the efficacy of RT for HO prevention in ambulatory adults after traumatic hip injury to a population of children with central nervous system injury and NHD may be premature. Additional studies are needed to clarify optimal prevention of HO in this population. LEVEL OF EVIDENCE: Level III-therapeutic retrospective comparative study.

Sonography of Abdominal Pain in Children: Appendicitis and Its Common Mimics.

Abdominal pain is very common in the pediatric population (<18 years of age). Sonography is a safe modality that can often differentiate the frequently encountered causes of abdominal pain in children. This pictorial essay will discuss the sonographic findings of acute appendicitis, including the imaging appearance of a perforated appendicitis. It will also present the sonographic features of the relatively common mimics of appendicitis, such as mesenteric adenitis/gastroenteritis, intussusception, Meckel diverticulum, and ovarian torsion.

Current methods for reducing intussusception: survey results.

BACKGROUND: Intussusception is a common pediatric abdominal emergency, treated with image-guided reduction. Available techniques include fluoroscopic and ultrasonographic monitoring of liquid and air. OBJECTIVE: The purpose of this study was to determine current practices and establish trends by comparing our findings with reports of previous surveys. MATERIALS AND METHODS: This study is based on an e-mail survey sent to all 1,538 members of the Society for Pediatric Radiology. It included questions about demographics, presence of parents/surgeon during procedure, patient selection/preparation, use of sedation, preferred methods of reduction and technical details, approach to unsuccessful reduction, and self-reported incidence of success/perforation. RESULTS: The 456 respondents (30%) reported attempting 3,834 reductions in the preceding 12 months. Of these, 96% use fluoroscopy and 4% use US guidance for reduction; 78% use air, 20% prefer fluid; 75% require intravenous access; 63% expect a surgeon to be present in hospital; 93% do not sedate. Although inflating a rectal balloon is controversial, 39% do so, and 50% employ a pressure-release valve. Seventy-two percent attempt reductions three times in the same position. In case of unsuccessful reductions, 64% wait and re-attempt later, 19% apply manual pressure, and 15% try again in left decubitus position. About 20% reattempt reduction after waiting 2 h or more. CONCLUSION: By providing a better understanding of both trends in and diversity of current practice, we hope to increase the confidence with which the individual practitioner will approach each case.

Nonsurgical management of childhood intussusception: retrospective comparison between sonographic and fluoroscopic guidance.

OBJECTIVES: The purpose of this study was to compare the effectiveness of sonography and fluoroscopy in guiding intussusception reduction and evaluate possible complications for each procedure. METHODS: A retrospective analysis was performed by reviewing 31 cases of intussusception diagnosed and managed between January 2009 and January 2014 at the University of California, Davis Children's Hospital, after obtaining approval from the Institutional Review Board. To eliminate other confounding factors related to technique and experience, only cases performed by 2 pediatric radiologists who exclusively used either fluoroscopy or sonography were compared. RESULTS: Fourteen patients (age range, 6-35 months) were treated by sonographic guidance using saline, and another 17 patients (age range, 2-57 months) were treated by fluoroscopy using either air or a water-soluble contrast agent. All 14 patients (100%) who underwent sonographically guided reduction were successfully treated without complications. Fourteen of the 17 patients (82%) who underwent fluoroscopic guidance had successful reductions. One complication of perforation was documented. CONCLUSIONS: Sonography and fluoroscopy are equally effective in the nonsurgical management of childhood intussusception. The absence of ionizing radiation and better visualization of possible pathologic lead points makes sonography the ideal method.

CT of the chest in suspected child abuse using submillisievert radiation dose.

The cornerstone of child abuse imaging is the skeletal survey, but initial imaging with radiographs may not demonstrate acute and non-displaced fractures, especially those involving the ribs. Given the high mortality of undiagnosed non-accidental trauma, timely diagnosis is crucial. CT is more sensitive in assessing rib fractures; however the effective radiation dose of a standard chest CT is high. We retrospectively identified four children (three boys, one girl; age range 1-4 months) admitted between January 2013 and February 2014 with high suspicion for non-accidental trauma from unexplained fractures of the long bones; these children all had CT of the chest when no rib fractures were evident on the skeletal survey. The absorbed radiation dose estimates for organs and tissue from the four-view chest radiographs and subsequent CT were determined using Monte Carlo photon transport software, and the effective dose was calculated using published tissue-weighting factors. In two children, CT showed multiple fractures of the ribs, scapula and vertebral body that were not evident on the initial skeletal survey. The average effective dose for a four-view chest radiograph across the four children was 0.29 mSv and the average effective dose for the chest CT was 0.56 mSv. Therefore the effective dose of a chest CT is on average less than twice that of a four-view chest radiograph. Our protocol thus shows that a reduced-dose chest CT may be useful in the evaluation of high specificity fractures of non-accidental trauma when the four-view chest radiographs are negative.

Optimizing bone surveys performed for suspected non-accidental trauma with attention to maximizing diagnostic yield while minimizing radiation exposure: utility of pelvic and lateral radiographs.

BACKGROUND: Skeletal surveys for non-accidental trauma (NAT) include lateral spinal and pelvic views, which have a significant radiation dose. OBJECTIVE: To determine whether pelvic and lateral spinal radiographs should routinely be performed during initial bone surveys for suspected NAT. MATERIALS AND METHODS: The radiology database was queried for the period May 2005 to May 2011 using CPT codes for skeletal surveys for suspected NAT. Studies performed for skeletal dysplasia and follow-up surveys were excluded. Initial skeletal surveys were reviewed to identify fractures present, including those identified only on lateral spinal and/or pelvic radiographs. Clinical information and MR imaging was reviewed for the single patient with vertebral compression deformities. RESULTS: Of the 530 children, 223 (42.1%) had rib and extremity fractures suspicious for NAT. No fractures were identified solely on pelvic radiographs. Only one child (<0.2%) had vertebral compression deformities identified on a lateral spinal radiograph. This infant had rib and extremity fractures and was clinically paraplegic. MR imaging confirmed the vertebral body fractures. CONCLUSION: Since no fractures were identified solely on pelvic radiographs and on lateral spinal radiographs in children without evidence of NAT, nor in nearly all with evidence of NAT, inclusion of these views in the initial evaluation of children for suspected NAT may not be warranted.

Pediatric soft tissue sarcomas.

After a brief discussion of the rarity of soft tissue sarcomas in children and of the limited ability of magnetic resonance imaging to provide a tissue diagnosis, this article discusses the incidence, presentation, treatment, prognosis, and imaging characteristics of the more common and unusual pediatric soft tissue sarcomas. It begins with extensive discussion of rhabdomyosarcoma, synovial sarcoma, and congenital/infantile fibrosarcoma. It then presents a more abbreviated discussion of uncommon tumors such as alveolar soft part sarcoma, epithelioid sarcoma, extraosseous Ewing's sarcoma, granulocytic sarcoma, hemangiopericytoma, liposarcoma, malignant fibrous histiocytoma, malignant peripheral nerve sheath tumor, and undifferentiated sarcoma.

Pediatric radiology fellows' experience with intussusception reduction.

BACKGROUND: Intussusception reduction allows young children to avoid surgery. However, graduating residents have had relatively little training in intussusception reduction and, for the most part, consider themselves ill-prepared to perform this procedure. OBJECTIVE: The goal of this study was to assess the extent of training in intussusception reduction during one year of a pediatric radiology fellowship and to determine whether graduating fellows consider themselves adequately trained in this technique. MATERIALS AND METHODS: Pediatric radiology fellows were surveyed during June 2010 and asked to characterize their fellowship, to indicate the number of intussusception reductions performed (both the total number and those performed with faculty oversight but without active faculty involvement), and to assess the adequacy of their training. RESULTS: There were 31 responses, representing almost 1/3 of current fellows. Pediatric radiology fellows perform on average 6.9 reductions, 3.8 of which are with faculty oversight but without active faculty involvement. Ninety percent consider themselves well-trained in the technique, whereas 10% are uncertain (none consider their training inadequate). CONCLUSION: Almost all pediatric radiology fellows consider their training in intussusception reduction to be adequate.

Radiology residents' experience with intussusception reduction.

BACKGROUND: Residents should be exposed to adequate procedural volume to act independently upon completion of training. Informal inquiry led us to question whether residents encounter enough intussusception reductions to become comfortable with the procedure. OBJECTIVE: We sought to determine radiology residents' exposure to intussusception reductions, and whether their experiences vary by region or institution. MATERIALS AND METHODS: U.S. radiology residency program directors were asked to encourage their residents to complete a 12-question online survey describing characteristics of their pediatric radiology department, experiences with intussusception reduction, and confidence in their own ability to perform the procedure. RESULTS: Six hundred sixty-four residents responded during the study period. Of those, 308 (46.4%) had not experienced an intussusception reduction, and 228 (34%) had experienced only one or two. Twenty-two percent of fourth-year residents had never experienced an intussusception reduction, and 21% had experienced only one. Among second- through fourth-year residents, only 99 (18.3%) felt confident that they could competently reduce an intussusception (P < 0.0001), and 336 (62.2%) thought they would benefit from a computer-assisted training model simulating intussusception reduction (P < 0.0001). CONCLUSION: Radiology residents have limited opportunity to learn intussusception reduction and therefore lack confidence. Most think they would benefit from additional training with a computer-simulation model.

Follow-up skeletal surveys for suspected non-accidental trauma: can a more limited survey be performed without compromising diagnostic information?

OBJECTIVE: Follow-up skeletal surveys have been shown to improve the rate of fracture detection in suspected cases of non-accidental trauma (NAT). As these studies are performed in a particularly radiosensitive population, it is important to evaluate if all of the (approximately 20) radiographs obtained at repeat skeletal survey are clinically useful. Our goal was to evaluate if certain radiographs can be excluded at follow-up skeletal survey without compromising the clinical efficacy. METHODS: This retrospective study included 22 cases of suspected NAT (average age 3.8 months, range 0.7-15 months) in which patients received both initial and follow-up bone surveys. The follow-up survey was performed an average of 16.7 days (range 11-29 days) after the initial survey. Radiographs were reviewed by 2 pediatric radiologists, with discrepancies resolved by consensus. In addition, we combined our data with data from all known previously published reports of follow-up skeletal surveys for NAT for meta-analysis. RESULTS: A total of 36 fractures were found on the initial bone survey in 16/22 patients (73%). Six patients had no fractures detected at initial survey. Follow-up bone surveys demonstrated an additional 3 fractures (2 extremities and 1 rib) in 3/22 cases (14%); 1 was in a patient whose initial survey was negative. No additional fractures in the skull, spine, pelvis, feet, or hands were detected in any case. In combination with patients reported in the literature (194 patients total) no new fracture of the skull, spine, pelvis, or hands was detected at follow-up survey. The skull, spine and pelvis radiographs are the highest dose-exposure studies of the skeletal survey. CONCLUSION AND PRACTICE IMPLICATIONS: If no injury is detected or suspected in the pelvis, spine, hands, or skull at initial bone survey for suspected NAT, a limited follow-up skeletal survey which excludes the pelvis, lateral spine, hands, and skull should be considered to limit radiation exposure without limiting diagnostic information.

Rib head protrusion into the central canal in type 1 neurofibromatosis.

BACKGROUND: Intraspinal rib head dislocation is an important but under-recognized consequence of dystrophic scoliosis in patients with neurofibromatosis 1 (NF1). OBJECTIVE: To present clinical and imaging findings of intraspinal rib head dislocation in NF1. MATERIALS AND METHODS: We retrospectively reviewed clinical presentation, imaging, operative reports and post-operative courses in four NF1 patients with intraspinal rib head dislocation and dystrophic scoliosis. We also reviewed 17 cases from the English literature. RESULTS: In each of our four cases of intraspinal rib head dislocation, a single rib head was dislocated on the convex apex of the curve, most often in the mid- to lower thoracic region. Cord compression occurred in half of these patients. Analysis of the literature yielded similar findings. Only three cases in the literature demonstrates the MRI appearance of this entity; most employ CT. All of our cases include both MRI and CT; we review the subtle findings on MRI. CONCLUSION: Although intraspinal rib head dislocation is readily apparent on CT, sometimes MRI is the only cross-sectional imaging performed. It is essential that radiologists become familiar with this entity, as subtle findings have significant implications for surgical management.

An interactive teaching device simulating intussusception reduction.

Intussusception is relatively uncommon, occurring in 0.5 to 2.3 cases per 1,000 live births in the USA. Radiology residents, therefore, have few opportunities to participate in intussusception reduction during training, and practicing radiologists encounter it infrequently. Training is essential, as successful reduction avoids surgery. The judgment involved in reducing an intussusception is best gained with experience. We developed a training device that simulates fluoroscopic intussusception reduction with air. The device consists of a doll that contains a cylinder with similar stress and strain characteristics to the human colon. The trainee pumps air into the cylinder through a rectal tube using a standard hand-held air reduction pump. A sensor measures the pressure within the chamber and transmits readings to a computer, which displays images from actual intussusception reductions based on the pressure maintained within the device. A random component in the software gives the user a new experience each time and models uncertainties in the actual reduction process, including perforation. This intussusception reduction simulator can enhance resident education, giving residents the opportunity to practice this technique before employing it on a real patient. The simulator can also help practicing radiologists become more comfortable with intussusception air reduction.