Biomechanical Function and Size of the Anteromedial and Posterolateral Bundles of the ACL Change Differently with Skeletal Growth in the Pig Model.

BACKGROUND: ACL injuries are becoming increasingly common in children and adolescents, but little is known regarding age-specific ACL function in these patients. To improve our understanding of changes in musculoskeletal tissues during growth and given the limited availability of pediatric human cadaveric specimens, tissue structure and function can be assessed in large animal models, such as the pig. QUESTIONS/PURPOSES: Using cadaveric porcine specimens ranging throughout skeletal growth, we aimed to assess age-dependent changes in (1) joint kinematics under applied AP loads and varus-valgus moments, (2) biomechanical function of the ACL under the same loads, (3) the relative biomechanical function of the anteromedial and posterolateral bundles of the ACL; and (4) size and orientation of the anteromedial and posterolateral bundles. METHODS: Stifle joints (analogous to the human knee) were collected from female Yorkshire crossbreed pigs at five ages ranging from early youth to late adolescence (1.5, 3, 4.5, 6, and 18 months; n = 6 pigs per age group, 30 total), and MRIs were performed. A robotic testing system was used to determine joint kinematics (AP tibial translation and varus-valgus rotation) and in situ forces in the ACL and its bundles in response to applied anterior tibial loads and varus-valgus moments. To see if morphological changes to the ACL compared with biomechanical changes, ACL and bundle cross-sectional area, length, and orientation were calculated from MR images. RESULTS: Joint kinematics decreased with increasing age. Normalized AP tibial translation decreased by 44% from 1.5 months (0.34 ± 0.08) to 18 months (0.19 ± 0.02) at 60° of flexion (p < 0.001) and varus-valgus rotation decreased from 25° ± 2° at 1.5 months to 6° ± 2° at 18 months (p < 0.001). The ACL provided the majority of the resistance to anterior tibial loading at all age groups (75% to 111% of the applied anterior force; p = 0.630 between ages). Anteromedial and posterolateral bundle function in response to anterior loading and varus torque were similar in pigs of young ages. During adolescence (4.5 to 18 months), the in situ force carried by the anteromedial bundle increased relative to that carried by the posterolateral bundle, shifting from 59% ± 22% at 4.5 months to 92% ± 12% at 18 months (data for 60° of flexion, p < 0.001 between 4.5 and 18 months). The cross-sectional area of the anteromedial bundle increased by 30 mm throughout growth from 1.5 months (5 ± 2 mm) through 18 months (35 ± 8 mm; p < 0.001 between 1.5 and 18 months), while the cross-sectional area of the posterolateral bundle increased by 12 mm from 1.5 months (7 ± 2 mm) to 4.5 months (19 ± 5 mm; p = 0.004 between 1.5 and 4.5 months), with no further growth (17 ± 7 mm at 18 months; p = 0.999 between 4.5 and 18 months). However, changes in length and orientation were similar between the bundles. CONCLUSION: We showed that the stifle joint (knee equivalent) in the pig has greater translational and rotational laxity in early youth (1.5 to 3 months) compared with adolescence (4.5 to 18 months), that the ACL functions as a primary stabilizer throughout growth, and that the relative biomechanical function and size of the anteromedial and posterolateral bundles change differently with growth. CLINICAL RELEVANCE: Given the large effects observed here, the age- and bundle-specific function, size, and orientation of the ACL may need to be considered regarding surgical timing, graft selection, and graft placement. In addition, the findings of this study will be used to motivate pre-clinical studies on the impact of partial and complete ACL injuries during skeletal growth.

Somatic PTPN11 Mutation in a Child With Neuroblastoma and Protein Losing Enteropathy.

Neuroblastoma and protein losing enteropathy (PLE) are diagnoses commonly seen by oncologists and gastroenterologists, respectively. The concurrence of these 2 entities is rare, and not well explained. We describe the sixth case of PLE in a child with neuroblastoma, and the first for which genetic information is available. Tumor DNA had a mutation in the PTPN11 gene, which has been described in neuroblastoma, and in Noonan syndrome-a diagnosis in which neuroblastoma and PLE independently have been reported. Constitutional DNA was normal. Genetic studies in future patients will be needed to support the link between neuroblastoma and PLE.

Safety of contrast-enhanced ultrasound in children for non-cardiac applications: a review by the Society for Pediatric Radiology (SPR) and the International Contrast Ultrasound Society (ICUS).

The practice of contrast-enhanced ultrasound in children is in the setting of off-label use or research. The widespread practice of pediatric contrast-enhanced US is primarily in Europe. There is ongoing effort by the Society for Pediatric Radiology (SPR) and International Contrast Ultrasound Society (ICUS) to push for pediatric contrast-enhanced US in the United States. With this in mind, the main objective of this review is to describe the status of US contrast agent safety in non-cardiac applications in children. The five published studies using pediatric intravenous contrast-enhanced US comprise 110 children. There is no mention of adverse events in these studies. From a European survey 948 children can be added. In that survey six minor adverse events were reported in five children. The intravesical administration of US contrast agents for diagnosis of vesicoureteric reflux entails the use of a bladder catheter. Fifteen studies encompassing 2,951 children have evaluated the safety of intravesical US contrast agents in children. A European survey adds 4,131 children to this group. No adverse events could be attributed to the contrast agent. They were most likely related to the bladder catheterization. The existing data on US contrast agent safety in children are encouraging in promoting the widespread use of contrast-enhanced US.

Near-Peer Teaching in Radiology Symposia: A Success Story in Residents as Teachers.

INTRODUCTION: Peer learning and near-peer teaching have been described in many specialties, less so in Radiology. We present near-peer teaching whereby residents present a series of didactic sessions at the course outset in the form of "symposia" and perform a scholarly activity in the form of teaching. We aim to demonstrate how near-peer teaching in symposia front-loaded within an introductory radiology course can improve medical student satisfaction. METHOD: A total of 169 students were enrolled over a period of 3 years, 55 before (2017-2018) and 114 (2018-2020) after the introduction of the symposium. Anonymous course evaluations were collected from all students. In addition, 240 fourth-year medical students who also attended symposium lectures received satisfaction surveys in 2019 and 2020. RESULTS: All (169/169, 100%) students taking the course evaluated it. Overall evaluation scores rose from 8.3/10 to 9.0/10 post-symposia. Among student satisfaction surveys, 89/240 (37%) specifically commented on symposia; 91% (80/89) of those found symposia very or extremely informative. 29/71 (41%) of all residents were able to participate in the symposia, 20/29 in multiple years throughout residency, allowing them to fulfill the Accreditation Council for Graduate Medical Education interpersonal and communication skills core competencies and meet scholarly activity requirements. CONCLUSION: Near-peer teaching in the form of resident-taught interactive didactics grouped in symposia can have a positive outcome on medical student satisfaction.

Sex-specific biomechanics and morphology of the anterior cruciate ligament during skeletal growth in a porcine model.

Pediatric anterior cruciate ligament (ACL) injuries are on the rise, and females experience higher ACL injury risk than males during adolescence. Studies in skeletally immature patients indicate differences in ACL size and joint laxity between males and females after the onset of adolescence. However, functional data regarding the ACL and its anteromedial and posterolateral bundles in the pediatric population remain rare. Therefore, this study uses a porcine model to investigate the sex-specific morphology and biomechanics of the ACL and its bundles throughout skeletal growth. Hind limbs from male and female Yorkshire pigs aged early youth to late adolescence were imaged using magnetic resonance imaging to measure the size and orientation of the ACL and its bundles, then biomechanically tested under anterior-posterior drawer using a robotic testing system. Joint laxity decreased (p < 0.001) while joint stiffness increased (p < 0.001) throughout skeletal growth in both sexes. The ACL was the primary stabilizer against anterior tibial loading, while the functional role of the anteromedial bundle increased with age (p < 0.001), with an earlier increase in males. ACL and posterolateral bundle cross-sectional area and ACL and anteromedial bundle length were larger in males than females during adolescence (p < 0.01 for all), while ACL and bundle sagittal angle remained similar between sexes. Additionally, in situ ACL stiffness versus cross-sectional area regressions were significant across skeletal growth (r2 = 0.75, p < 0.001 in males and r2 = 0.64, p < 0.001 in females), but not within age groups. This study has implications for age and sex-specific surgical intervention strategies and suggests the need for human studies.

Age- and sex-specific differences in ACL and ACL bundle size during adolescent growth.

Anterior cruciate ligament (ACL) injuries are increasingly common in adolescents, and injuries in this age-group are associated with many unique challenges. Recent large animal studies suggest that the size and function of the major bundles of the ACL change differently throughout skeletal growth. To better aid clinical treatment of pediatric partial ACL tears and better predict outcomes from age-specific treatments, there is a need to measure changes in ACL bundle size in humans during growth. As such, the objective of this study was to compare changes in the length and cross-sectional area (CSA) of the ACL and its primary bundles in adolescent human subjects. Magnetic resonance imaging (MRI) scans were analyzed to determine the visibility and integrity of the ACL and its anteromedial and posterolateral bundles. MRI scans were considered from a retrospective database of subjects ranging from 10 to 18 years of age. The ACL and its anteromedial and posterolateral bundles were segmented and reconstructed into 3D models, and length and CSA were calculated. Total ACL length and CSA were greater in males compared with females, with a statistically significant interaction between age and sex for CSA. Sex had a significant effect on the CSA of both bundles. These sex-dependent differences emerge with moderate to large effect sizes (range: d = 0.50 to d = 1.23) beginning around 13 years of age. Along with ACL bundle structure-function relationships previously established in preclinical animal models, these findings may point toward biomechanical changes in the adolescent human ACL.

Student-led peer review of an online teaching file: perspectives after 2 years.

PROBLEM: Opportunities for self-directed learning were missing from our medical school curriculum in general and on our radiology electives specifically. Our objective was to explore the feasibility and benefits of using medical students in the development of our student-created teaching files. APPROACH: In 2018, a website was developed at our institution to support medical student radiology education and create a repository for the online publication of student-developed teaching cases. Students participating in radiology clerkships at our institution had an opportunity to submit case presentations for publication to our online teaching file following peer review. The medical students participated in the peer review process facilitated by the faculty director of radiology undergraduate medical education. The faculty member oversaw the training of new student editors and the development of a peer review guide. OUTCOMES: The peer review guide included goals of the teaching file project and direction regarding the peer review process. Student editors were trained using the peer review guide in conjunction with individual meetings with the faculty mentor. At twenty-four months, 82 student-developed cases had been published to the online teaching file following medical student peer review. The teaching file had garnered 3884 page views. NEXT STEPS: The medical student-led peer review process meets core competencies in self-directed learning. The authors plan to explore the application of peer-assisted learning theories to the editing and peer-review process.

Medical student imaging case files in the cloud.

BACKGROUND: Millennial digital learners value meaningful work, immediate feedback, collaborative communication and technology implementation. A student-produced digital imaging teaching case file-centric flipped curriculum offers these benefits. Our questions included: (i) is a cloud-based website platform supporting the online publication of student-selected and student-submitted teaching cases feasible; and (ii) what were the impressions of students of this educational intervention? METHODS: An open-source medical student-centric radiology website was created with limited-access cloud upload capability, with site analytics continuously recorded. Medical students submitted de-identified radiology cases on a topic of their choosing, for peer review and publication. By making the host site publicly accessible, we empowered students to list their publication(s) on resumes. Following six blocks of the 2018/19 academic year after implementation, an electronic survey was sent to the eligible medical student cohort who had were enrolled in a radiology elective in order to assess the effectiveness of the intervention (n = 107). RESULTS: The survey response rate was 52% (n = 56), of which 98% participated (n = 55) and 75% completed a teaching file (n = 42). The students assessed their ability to systematically review imaging, communicate pertinent clinical information, appropriately order imaging, correctly use the ACR Appropriateness Criteria® , consider procedure costs, consider procedure risks, consider procedure benefits, evaluate effectiveness and identify who to direct questions to regarding correct study. Students reported answers on a seven-point Likert scale. Data scores ranged from 5.28 (agree) to 6.71 (strongly agree) across all categories. CONCLUSIONS: Our successful student-developed teaching file takes advantage of digital radiology and the educational tools favoured by millennials. This activity meets core competencies in self-directed and lifelong learning.

Diagnostic ionizing radiation exposure in a population-based sample of children with inflammatory bowel diseases.

OBJECTIVES: The degree of diagnostic radiation exposure in children with inflammatory bowel diseases (IBD) is largely unknown. In this study, we describe this exposure in a population-based sample of children with IBD and determine the characteristics associated with moderate radiation exposure. METHODS: We ascertained radiological study use, demographic characteristics, IBD medication use, and the requirement for hospitalization, emergency department (ED) encounter, or inpatient gastrointestinal surgery among children with IBD within a large insurance claims database. Characteristics associated with moderate radiation exposure (at least one computed tomography (CT) or three fluoroscopies over 2 years) were determined using logistic regression models. RESULTS: We identified 965 children with Crohn's disease (CD) and 628 with ulcerative colitis (UC). Over 24 months, 34% of CD subjects and 23% of UC subjects were exposed to moderate diagnostic radiation (odds ratio (OR) 1.71, 95% confidence interval (CI), 1.36 - 2.14). CT accounted for 28% and 25% of all studies in CD and UC subjects, respectively. For CD subjects, moderate radiation exposure was associated with hospitalization (OR 4.89, 95% CI 3.37 - 7.09), surgery (OR 2.93, 95% CI 1.59 - 5.39), ED encounter (OR 2.65, 95% CI 1.93 - 3.64), oral steroids (OR 2.25, 95% CI 1.50 - 3.38), and budesonide (OR 1.80, 95% CI 1.10 - 3.06); an inverse association was seen with immunomodulator use (OR 0.67, 95% CI 0.47 - 0.97). Except for oral steroids and immunomodulators, similar relationships were seen in UC. CONCLUSIONS: A substantial proportion of children with IBD are exposed to moderate amounts of radiation as a result of diagnostic testing. This high utilization may impart long-term risk, given the chronic nature of the disease.

Tissue-specific changes in size and shape of the ligaments and tendons of the porcine knee during post-natal growth.

Prior studies have analyzed growth of musculoskeletal tissues between species or across body segments; however, little research has assessed the differences in similar tissues within a single joint. Here we studied changes in the length and cross-sectional area of four ligaments and tendons, (anterior cruciate ligament, patellar tendon, medial collateral ligament, lateral collateral ligament) in the tibiofemoral joint of female Yorkshire pigs through high-field magnetic resonance imaging throughout growth. Tissue lengths increased by 4- to 5-fold from birth to late adolescence across the tissues while tissue cross-sectional area increased by 10-20-fold. The anterior cruciate ligament and lateral collateral ligament showed allometric growth favoring change in length over change in cross-sectional area while the patellar tendon and medial collateral ligament grow in an isometric manner. Additionally, changes in the length and cross-sectional area of the anterior cruciate ligament did not increase as much as in the other ligaments and tendon of interest. Overall, these findings suggest that musculoskeletal soft tissue morphometry can vary within tissues of similar structure and within a single joint during post-natal growth.

Circulating biomarkers in extremely preterm infants associated with ultrasound indicators of brain damage.

AIM: To assess to what extent the blood concentrations of proteins with neurotrophic and angiogenic properties measured during the first postnatal month convey information about the risk of sonographically-identified brain damage among very preterm newborns. METHODS: Study participants were 1219 children who had a cranial ultrasound scan during their stay in the intensive care nursery and blood specimens collected on 2 separate days at least a week apart during the first postnatal month. Concentrations of selected proteins in blood spots were measured with electrochemiluminescence or with a multiplex immunobead assay and the risks of cranial ultrasound images associated with top-quartile concentrations were assessed. RESULTS: High concentrations of multiple inflammation-related proteins during the first 2 postnatal weeks were associated with increased risk of ventriculomegaly, while high concentrations of just 3 inflammation-related proteins were associated with increased risk of an echolucent/hypoechoic lesion (IL-6, IL-8, ICAM-1), especially on day 7. Concomitant high concentrations of IL6R and bFGF appeared to modulate the increased risks of ventriculomegaly and an echolucent lesion associated with inflammation. More commonly high concentrations of putative protectors/repair-enhancers did not appear to diminish these increased risks. CONCLUSION: Our findings provide support for the hypothesis that endogenous proteins are capable of either protecting the brain against damage and/or enhancing repair of damage.

Hypophosphatemic rickets in opsismodysplasia.

BACKGROUND: Opsismodysplasia is a rare spondylo(epi)chondrodysplasia characteristized by delayed skeletal maturation and a constellation of dysplastic features. Although metaphyseal irregularities/cupping have been noted, neither renal phosphate wasting nor rickets have previously been reported. OBJECTIVE: To evaluate hypophosphatemia and rickets in opsismodysplasia. PATIENTS: Two girls with opsismodysplasia presenting with hypophoshpatemia by 3 years of age. METHODS: Routine biochemistries to assess hypophosphatemia and renal phosphate wasting; radiographs (rachitic changes) and DEXA scan (BMD); FGF23 levels, PHEX and FGF23 gene analyses performed (Patient 1). RESULTS: Both children had hypophosphatemia, decreased TRP, and rickets. Oral phosphorus and calcitriol improved metaphyseal mineralization, yet serum phosphate levels remained relatively low and renal phosphate wasting persisted. PHEX and FGF23 gene analyses were negative, whereas serum FGF23 levels were markedly elevated in Patient 1. CONCLUSION: We now demonstrate an association between opsismodysplasia, hypophosphatemic rickets, and FGF23 elevation. Screening phosphorus levels may thus uncover a potentially treatable component of this disease.

Pediatric Applications of Hybrid PET/MR Imaging.

Hybrid PET/MR imaging systems have recently become available for clinical practice. The simultaneous physiologic and anatomic imaging offers the potential to reduce radiation dose and other advantages for pediatric patients. Issues more unique to pediatric imaging, however, must also be addressed, including imaging time and disease sensitivity. Combined with newer tracers and a concerted multidisciplinary effort, the approach has the potential to substantially improve the imaging of a variety of pediatric diseases.

Orientation changes in the cruciate ligaments of the knee during skeletal growth: A porcine model.

Musculoskeletal injuries in pediatric patients are on the rise, including significant increases in anterior cruciate ligament (ACL) injuries. Previous studies have found major anatomical changes during skeletal growth in the soft tissues of the knee. Specifically, the ACL and the posterior cruciate ligament (PCL) change in their relative orientation to the tibial plateau throughout growth. In order to develop age-specific treatments for ACL injuries, the purpose of this study was to characterize orientation changes in the cruciate ligaments of the Yorkshire pig, a common pre-clinical model, during skeletal growth in order to verify the applicability of this model for pediatric musculoskeletal studies. Hind limbs were isolated from female Yorkshire pigs ranging in age from newborn to late adolescence and were then imaged using high field strength magnetic resonance imaging. Orientation changes were quantified from the magnetic resonance images using image segmentation software. Statistically significant increases were found in the coronal and sagittal angles of the ACL relative to the tibial plateau during pre-adolescent growth. Additional changes were observed in the PCL angle, Blumensaat angle, intercondylar roof angle, and the aspect ratio of the intercondylar notch. Only the sagittal angle of the ACL relative to the tibial plateau experienced statistically significant changes through late adolescence. The age-dependent properties of the ACL and PCL in the female pig mirrored results found in female human patients, suggesting that the porcine model may provide a pre-clinical platform to study the cruciate ligaments during skeletal growth. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2725-2732, 2017.

Lung radiology and pulmonary function of children chronically exposed to air pollution.

We analyzed the chest radiographs (CXRs) of 249 clinically healthy children, 230 from southwest Mexico City and 19 from Tlaxcala. In contrast to children from Tlaxcala, children from southwest Mexico City were chronically exposed to ozone levels exceeding the U.S. National Ambient Air Quality Standards for an average of 4.7 hr/day and to concentrations of particulate matter (PM) with aerodynamic diameters

Multifocal bone marrow involvement in cat-scratch disease.

We describe 2 children with prolonged fever of unknown origin and prominent skeletal pain who had multifocal bone disease caused by Bartonella infection. Initial radiologic studies, including plain films, radionuclide scintigraphy and computed tomography, yielded negative results. In both cases, magnetic resonance imaging revealed multiple enhancing bone marrow lesions consistent with clinical symptoms. Microbiologic diagnoses were established serologically.

Respiratory damage in children exposed to urban pollution.

Southwest Metropolitan Mexico City (SWMMC) children are chronically exposed to complex mixtures of air pollutants. In a cross-sectional arm of our study, we investigated the association between exposure to SWMMC atmosphere and nasal abnormalities, hyperinflation, and interstitial markings assessed by chest X-rays, lung function changes, several serum cytokines, and endothelin-1 in 174 children aged 5-17 years vs. 27 control children residents in low-polluted areas. Control children had no nasal lesions, and only one child showed an abnormal chest X-ray. SWMMC children exhibited nasal abnormalities (22%), hyperinflation (67%), interstitial markings (49%), and a mild restrictive pattern by spirometry (10%). Interstitial markings were associated with a decrease in predicted values of FEF(25-75), FEF(75), and the FEV(1)/FVC ratio. Boys had a higher probability of developing interstitial markings with age (P = 0.004). Blood smear findings included toxic granulations in neutrophils and schistocytes. SWMMC children had more serum IL10 and IL6 and less IL8 than controls. In a longitudinal arm of our study, we found a significant seasonal drop in FVC and FEV(1) associated with a 6-month period of high ozone and PM(10) levels. Our data strongly suggest that a lifelong exposure to urban air pollution causes respiratory damage in children. Moreover, a cytokine network becomes imbalanced, with a shift towards upregulation of anti-inflammatory cytokines. Consequently, these children are potentially at risk for developing chronic lung disease and other systemic effects later in life.

Fibular Hemimelia: More Than Just An Absent Bone.

Fibular hemimelia is a congenital deficiency or absence of the fibula. There is a spectrum of disease from mild fibular hypoplasia to fibular aplasia. The ipsilateral tibia may be hypoplastic, bowed or normal. Fibular hemimelia can be an isolated deformity of the lower leg but frequently it is associated with proximal focal femoral deficiency, deficiencies of the lateral aspect of the foot, or is part of a malformation syndrome. In this article, we review the embryology of the extremities, discuss proposed etiologies for fibular hemimelia, highlight associated abnormalities, and present the radiographic and imaging findings. Surgical treatment options and long-term outcomes are discussed.

MR imaging of the pediatric liver.

Applications of MR imaging of the pediatric abdomen are expanding rapidly. New techniques of MR imaging, such as MRA or MRCP, are becoming commonplace. MR imaging is particularly helpful in the diagnosis and characterization of liver and biliary tree disease in children. Consistent and reproducible quality imaging is achieved with faster imaging sequences tailored to reduce motion artifacts. The lack of radiation, the ability to directly acquire multiple imaging planes, and the superior contrast resolution, particularly with the administration of gadolinium, have contributed to the acceptance of MR imaging as an invaluable tool in the pediatric age group.

Computed tomography reflects lower airway inflammation and tracks changes in early cystic fibrosis.

RATIONALE: Detecting and tracking early cystic fibrosis (CF) lung disease are difficult due to lack of sensitive markers of airway dysfunction. OBJECTIVES: The goals were to detect regional distribution of airway disease through high-resolution computed tomography, correlate abnormalities to lower airway inflammation/infection, and compare computed tomography findings before and after intravenous antibiotic therapy in children with CF younger than 4 years experiencing a pulmonary exacerbation. METHODS: High-resolution computed tomography was performed in 17 children scheduled for bronchoscopy. The radiologist identified the lobes with the "greatest" and "least" disease based on computed tomography, and bronchoalveolar lavage was performed in these areas. In 13 subjects, imaging was repeated after antibiotic completion. Modified Brody scores were assigned by two radiologists. MEASUREMENTS AND MAIN RESULTS: The lobe with greatest disease was predominantly localized to the right and had higher modified Brody scores, indicating more severe abnormalities (p < 0.01), compared with the lobe with least disease. The total modified Brody score (p < 0.01), hyperinflation subscore (p < 0.01), and bronchial dilatation/bronchiectasis subscore (p < 0.01) improved after antibiotics and intensified airway clearance. Interleukin-8 levels (p < 0.01) and % neutrophils (p = 0.04) were increased in the lobe with greatest disease compared with the lobe with least disease. CONCLUSIONS: These results indicate that, in young children with CF experiencing a pulmonary exacerbation, computed tomography detects regional differences in airway inflammation, may be a sensitive outcome to evaluate therapeutic interventions, and identifies early lung disease as being more prominent on the right.