Whole-body MR imaging in evaluation of children with juvenile dermatomyositis.

PURPOSE: To evaluate the whole-body MRI (WBMRI) findings in children with juvenile dermatomyositis (JDM) and correlate them with clinical and laboratory results. METHOD: We conducted the present prospective study from October 2019 to September 2021. Thirty children (8.2 ± 3.88 years) with a diagnosis of JDM based on EULAR/ACR classification criteria underwent WBMRI using short tau inversion recovery, diffusion-weighted, and T1 modified DIXON (precontrast and postcontrast) sequences. WBMRI scans were analysed independently by two radiologists for abnormal signal intensity and enhancement in the different muscle groups. Radiological findings were correlated with clinical examination, muscle enzymes, and inflammatory markers. RESULTS: WBMRI revealed abnormal signal intensity and diffusion restriction, predominantly in the thigh (n = 21, 70 % children), calf (n = 18, 60 % children), and hip (n = 16, 53.3 % children) muscles. A significant positive correlation was observed between the serum total creatinine kinase and lactic dehydrogenaselevels, with altered signal intensity and diffusion restriction in the paraspinal and thigh muscles. Diffusion restriction in the hip and calf muscles also showed significant positive correlations with these enzymes. Significant positive correlations were detected between lower limb muscle strength and altered signal intensity and diffusion restriction in the thigh (p = 0.023) and calf (p = 0.002) muscles. Postcontrast images did not yield any additional useful information. CONCLUSIONS: WBMRI provided useful information in evaluation of the extent and distribution of findings in children with JDM. There were significant positive correlations between MRI findings and muscle enzymes and clinical examination results. The addition of contrast to the WBMRI protocol did not provide any additional advantage.

Safety of gadoterate meglumine in children younger than 2 years of age.

BACKGROUND: Few studies on the safety of gadolinium-based contrast agents have been performed in children with even fewer focusing on children younger than 2 years of age. OBJECTIVE: To assess the safety of gadoterate meglumine (Dotarem) in patients younger than 2 years of age by evaluating adverse events following contrast administration. MATERIALS AND METHODS: Pediatric patients younger than 2 years of age undergoing magnetic resonance imaging (MRI) with and without contrast were prospectively enrolled and received a weight-based intravenous dose of gadoterate meglumine (0.1 mmol/kg). The occurrence of adverse events was assessed at the time of injection, 2 h after MRI, and by phone contact using a standard questionnaire 24 h after MRI. Adverse events were documented including the time of onset, duration of symptoms, intensity, causality and subsequent outcome. Descriptive statistics were used to characterize patient information. RESULTS: One hundred fifty exams were completed in 150 patients (median age: 12.1 months, age range: 0.25-23 months; males: 56%). Almost all patients (97.3%) received sedation/anesthesia before and during MRI. Thirty-four adverse events were reported in 23 patients overall (15.3%; male: 73.9%; median age: 11 months, age range: 3-23 months). Within the initial 2 h after the injection, there was one report of transient flushing/warmth and one report of vomiting, the latter of which was related to drinking formula too soon after anesthesia. Twenty-two patients (14.7%), who had all received sedation/anesthesia, experienced minor adverse events within 24 h, most physiological. Fourteen patients (9.3%) reported emesis, eight (5.3%) reported transient flushing/warmth, seven (4.7%) reported nausea, one (0.7%) reported altered taste and one (0.7%) reported dizziness. No patient experienced anaphylaxis. Two patients (1.3%) reported allergic-like reactions, which consisted of wheezing or sneezing. CONCLUSION: No patient experienced adverse events directly related to gadoterate meglumine. Only two adverse events were reported to have occurred in the initial 2 h after the exam, while the rest were reported on the 24-h follow-up call. The higher reported rate of adverse events in this study may be related to concomitant sedation/anesthesia as well as to overreporting from parents on the 24-h follow-up questionnaire. The study confirms a good safety profile for gadoterate meglumine in this very sensitive population.

Diagnostic accuracy of non-contrast magnetic resonance enterography in detecting active bowel inflammation in pediatric patients with diagnosed or suspected inflammatory bowel disease to determine necessity of gadolinium-based contrast agents.

BACKGROUND: Pediatric patients with inflammatory bowel disease (IBD) are at increased risk of gadolinium deposition given the potential need for multiple contrast-enhanced magnetic resonance enterography (MRE) exams over their lifetime. OBJECTIVE: To determine whether gadolinium-based contrast agents are necessary in assessing active bowel inflammation on MRE in pediatric patients with known or suspected IBD. MATERIALS AND METHODS: We conducted a retrospective study of 77 patients (7-18 years; 68.8% male) with known (n=58) or suspected (n=19) IBD and endoscopy with biopsy performed within 30 days of MRE without and with contrast evaluated bowel and non-bowel findings. During three visual analysis sessions, two radiologists reviewed pre-, post-, and pre-/post-contrast MRE images. A third radiologist independently reviewed 27 studies to assess inter-reader reliability. We used Cohen kappa (κ), Fleiss kappa, (κF), McNemar test, and sensitivity and specificity to compare MRE readings to combined endoscopic/histopathological findings (the reference standard). RESULTS: The pre- and pre-/post-contrast-enhanced MRE vs. combined endoscopic/histopathological results had moderate agreement (85.7%; κ 0.713, P<0.001; P-value 0.549). Compared to combined endoscopy/histopathology, pre- vs. pre-/post-contrast sensitivity (67%, confidence interval [CI] 0.53-0.79 vs. 67%, CI 0.53-0.79) and specificity (80%, CI 0.59-0.92 vs. 68%, CI 0.46-0.84) varied little (κ 0.42, P<0.001 and κ 0.32, P=0.003, respectively). The three readers had moderate agreement (85.2%; κ 0.695, P=0.001; P-value 0.625). More penetrating complications were identified following contrast administration (P-value 0.04). CONCLUSION: Use of a contrast agent does not improve the detection of active inflammation in the terminal ileum and colon compared to non-contrast MRE, although use of a contrast agent does aid in the detection of penetrating disease.

Pediatric cardiac tumors: clinical and imaging features.

Cardiac tumors in children are rare, are more commonly benign, and differ in types when compared with those in adults. Rhabdomyoma, teratoma, and fibroma are the most common cardiac tumors in fetuses and neonates. In infants and children, the most common cardiac tumors are rhabdomyoma and fibroma, which are benign primary cardiac tumors, whereas in adults, thrombus is the most common cardiac mass and myxoma is the most common primary cardiac tumor. Sarcomas are the most common primary malignant cardiac tumors in both children and adults. Metastatic cardiac tumors are less common in children than in adults and include sarcoma, lymphoma, testicular cancer, and Wilms tumor. Patients with cardiac tumors can be asymptomatic or may present with murmur, arrhythmia, heart failure, or sudden death. Echocardiography is the primary modality for initial evaluation of symptomatic patients. Cardiac magnetic resonance imaging provides further characterization of cardiac masses and tumors for diagnostic purposes and can be used to assess cardiac and extracardiac involvement for treatment planning. Treatment varies from conservative management or surgical resection to transplantation, depending on the diagnosis and the patient's symptoms. Rhabdomyoma typically regresses spontaneously during early childhood and does not require surgical intervention if asymptomatic. However, fibroma is generally resected because it does not regress. An understanding of the types of cardiac tumors that occur in infants and children, their clinical implications and associations, and their imaging appearances will facilitate patient management.

Easier to swallow: pictorial review of structural findings of the pharynx at barium pharyngography.

Barium pharyngography remains an important diagnostic tool in the evaluation of patients with dysphagia. Pharyngography can not only help detect functional abnormalities but also help identify a wide spectrum of structural abnormalities in children and adults. These structural abnormalities may reflect malignant or nonmalignant oropharyngeal, hypopharyngeal, or laryngeal processes that deform or alter normal coated mucosal surfaces. Therefore, an understanding of the normal appearance of the pharynx at contrast material-enhanced imaging is necessary for accurate detection and interpretation of abnormal findings. Congenital malformations are more typically identified in the younger population; inflammatory and infiltrative diseases, trauma, foreign bodies, and laryngeal cysts can be seen in all age groups; and Zenker and Killian-Jamieson diverticula tend to occur in the older population. Squamous cell carcinoma is by far the most common malignant process, with contrast-enhanced imaging findings that depend on tumor location and morphology. Treatments of head and neck cancers include total laryngectomy and radiation therapy, both of which alter normal anatomy. Patients are usually evaluated immediately after laryngectomy to detect complications such as fistulas; later, pharyngography is useful for identifying and characterizing strictures. Deviation from the expected posttreatment appearance, such as irregular narrowing or mucosal nodularity, should prompt direct visualization to evaluate for recurrence. Contrast-enhanced imaging of the pharynx is commonly used in patients who present with dysphagia, and radiologists should be familiar with the barium pharyngographic appearance of the normal pharyngeal anatomy and of some of the processes that alter normal anatomy.

The copper toxicosis gene product Murr1 directly interacts with the Wilson disease protein.

Copper toxicosis in Bedlington terriers is an autosomal recessive disorder characterized by excessive hepatic copper accumulation in association with a marked decrease in biliary copper excretion. Recent genetic data have revealed that MURR1, a single copy gene on dog chromosome 10q26, is mutated in this disorder. This gene encodes a 190-amino acid open reading frame of unknown function that is highly conserved in vertebrate species. The Wilson disease protein is a copper transporting ATPase shown to play a critical role in biliary copper excretion. Here we demonstrate that the Wilson disease protein directly interacts with the human homologue of Murr1 in vitro and in vivo and that this interaction is mediated via the copper binding, amino terminus of this ATPase. Importantly, this interaction is specific for this copper transporter, a finding consistent with the observation that impaired copper homeostasis in affected terriers is confined to the liver. Our findings reveal involvement of Murr1 in the defined pathway of hepatic biliary copper excretion, suggest a potential mechanism for Murr1 function in this process, and provide biochemical evidence in support of the proposed role of the MURR1 gene in hepatic copper toxicosis.

The effect of DNA damage on the formation of protein/DNA complexes.

Many cellular functions including gene expression and chromosome structure are highly dependent upon the precise recognition and binding of specific DNA elements by regulatory and structural proteins. DNA damage that alters protein/DNA interactions therefore has the potential to disrupt normal cellular functions including proliferation. As a model to examine the interaction of proteins with damaged DNA, the binding of AP-1 transcription factor to cognate DNA elements with 8-oxoadenine, 8-oxoguanine and abasic sites was studied by gel mobility shift analysis. Of the three types of DNA damage only 8-oxoadenine was without effect on AP-1 binding. A single 8-oxoguanine could partially inhibit AP-1 binding when located at specific positions within and even adjacent to the conserved AP-1 binding sequence. Abasic site damage also demonstrated a position effect but with more overall inhibition. When 8-oxoguanine and abasic sites were combined to model the multiple damage sites produced by ionizing radiation there was a cumulative loss of AP-1 binding that appeared to be synergistic. These results suggest protein/DNA interactions can be quite sensitive to the site, degree, and type of DNA damage, even relatively minor modifications.