Denosumab-induced bone changes in a child: a case report.

We present the case of a 9-year-old girl who developed striking bone changes following two years of denosumab therapy for giant cell lesions of the jaw.

The impact of high-frequency transducers on the sonographic measurements of the pyloric muscle thickness in infants.

BACKGROUND: Ultrasound is the modality of choice for the diagnosis of hypertrophic pyloric stenosis (HPS). The evolution of high-frequency transducers in ultrasound has led to inconsistent ways of measuring the pylorus. OBJECTIVE: To standardize the measurements and evaluate the appearance of the normal and hypertrophied pylorus with high-frequency transducers. MATERIALS AND METHODS: We retrospectively analyzed abdominal ultrasounds of infants with suspected HPS from January 2019-December 2020. We classified the layers of the pylorus while assessing the stratified appearance. Two pediatric radiologists measured the muscle thickness of the pylorus independently by two methods for interrater agreement. Measurement (a) includes the muscularis propria and muscularis mucosa. Measurement (b) includes only the muscularis propria. We also evaluated the echogenicity of the muscularis propria. The interrater agreement, mean, range of the muscle thickness, and the diagnostic accuracy of the two sets of measurements were calculated. RESULTS: We included 300 infants (114 F:186 M), 59 with HPS and 241 normal cases. There was a strong agreement between the readers assessed in the first 100 cases, and ICC was 0.99 (95% CI, 0.98-0.99). Measurement (a), median thickness is 2.4 mm in normal cases and 4.8 mm in HPS. Measurement (b), median thickness is 1.4 mm in normal cases and 4.0 mm in HPS. Measurement (a) has an accuracy of 89.7% (95% CI, 85.7-92.8%) with 98.3% sensitivity and 87.6% specificity. Measurement (b) has an accuracy of 98.0% (95% CI, 95.7-99.3%) with 89.8% sensitivity and 100.0% specificity. The pylorus stratification is preserved in all normal cases and 31/59 (52.5%) cases of HPS. There was complete/partial loss of stratification in 28/59 (47.5%) cases of HPS. In all HPS cases, the muscularis propria was echogenic. CONCLUSION: Measuring the muscularis propria solely has a better diagnostic accuracy, decreasing the overlap of negative and positive cases. The loss of pyloric wall stratification and echogenic muscularis propria is only seen in HPS.

Association of new sonographic features with outcome in neonates with necrotizing enterocolitis.

BACKGROUND: We have recently noted some sonographic features in necrotizing enterocolitis that have received little or no attention in the current literature. These include thickening of the mesentery, hyperechogenicity of intraluminal intestinal contents, abnormalities of the abdominal wall, and poor definition of the intestinal wall. It has been our impression that the above four sonographic findings are generally seen in neonates with more severe necrotizing enterocolitis and may be useful in predicting outcome. OBJECTIVES: The aim of this study is, firstly, to review a large series of neonates, known to have clinical NEC, to document how frequently the above four sonographic features occur in neonates with necrotizing enterocolitis and, secondly, to determine whether they are predictive of outcome. MATERIALS AND METHODS: We retrospectively analyzed the clinical, radiographic, sonographic, and surgical findings in neonates with necrotizing enterocolitis between 2018 and 2021. The neonates were categorized into two groups based on outcome. Group A included neonates with a favorable outcome defined as successful medical treatment with no surgical intervention. Group B included neonates with an unfavorable outcome defined as failed medical treatment requiring surgery (for acute complications or late strictures) or death because of necrotizing enterocolitis. The sonographic examinations were reviewed with attention to the features of mesenteric thickening, hyperechogenicity of intraluminal intestinal contents, abnormalities of the abdominal wall, and poor definition of the intestinal wall. We then determined the association of these four findings with the two groups. RESULTS: We included 102 neonates with clinical necrotizing enterocolitis: 45 in group A and 57 in group B. Neonates in group B were born at a significantly earlier gestational age (median 25 weeks, range 22-38 weeks) and had a significantly lower birth weight (median 715.5 g, range 404-3120 g) than those in group A (median age 32 weeks, range 22-39 weeks, p = 0.003; median weight 1190 g, range 480-4500 g, p = 0.002). The four sonographic features were present in both study groups but with different frequency. More importantly, all four were statistically significantly more frequently present in neonates in group B compared to group A: (i) mesenteric thickening, A = 31 (69%), B = 52 (91%), p = 0.007; (ii) hyperechogenicity of intestinal contents, A = 16 (36%), B = 41 (72%), p = 0.0005; (iii) abnormalities of the abdominal wall, A = 11 (24%), B = 35 (61%), p = 0.0004; and (iv) poor definition of the intestinal wall, A = 7 (16%), B = 25 (44%), p = 0.005. Furthermore, the proportion of neonates with more than two signs was greater in group B compared to group A (Z test, p < 0.0001, 95% CI = 0.22-0.61). CONCLUSION: The four new sonographic features described were found to occur statistically significantly more frequently in those neonates with an unfavorable outcome (group B) than in those with a favorable outcome (group A). The presence or absence of these signs should be included in the sonographic report to convey the radiologists concern regarding the severity of the disease in every neonate, suspected or known to have necrotizing enterocolitis, as the findings may impact further medical or surgical management.

Ultrasound for necrotizing enterocolitis: how can we optimize imaging and what are the most critical findings?

Necrotizing enterocolitis (NEC) is a common condition in the neonatal intensive care unit that continues to present challenges in terms of diagnosis and management. Traditionally NEC has been diagnosed and managed by clinical and radiographic findings, but US has shown promise in characterizing and prognosticating NEC. In this manuscript we review the abdominal US technique for NEC, the clinical significance of individual sonographic findings of NEC, and how US can be integrated in the clinical decision process for diagnosing and managing NEC. We also discuss the potential value-added role of a limited abdominal US protocol that focuses on the sonographic findings most indicative of a poor prognosis to include pneumoperitoneum, complex free fluid and focal fluid collections.

Remote ischemic conditioning in necrotizing enterocolitis: study protocol of a multi-center phase II feasibility randomized controlled trial.

PURPOSE: Remote ischemic conditioning (RIC) is a maneuver involving brief cycles of ischemia reperfusion in an individual's limb. In the early stage of experimental NEC, RIC decreased intestinal injury and prolonged survival by counteracting the derangements in intestinal microcirculation. A single-center phase I study demonstrated that the performance of RIC was safe in neonates with NEC. The aim of this phase II RCT was to evaluate the safety and feasibility of RIC, to identify challenges in recruitment, retainment, and to inform a phase III RCT to evaluate efficacy. METHODS: RIC will be performed by trained research personnel and will consist of four cycles of limb ischemia (4-min via cuff inflation) followed by reperfusion (4-min via cuff deflation), repeated on two consecutive days post randomization. The primary endpoint of this RCT is feasibility and acceptability of recruiting and randomizing neonates within 24 h from NEC diagnosis as well as masking and completing the RIC intervention. RESULTS: We created a novel international consortium for this trial and created a consensus on the diagnostic criteria for NEC and protocol for the trial. The phase II multicenter-masked feasibility RCT will be conducted at 12 centers in Canada, USA, Sweden, The Netherlands, UK, and Spain. The inclusion criteria are: gestational age < 33 weeks, weight ≥ 750 g, NEC receiving medical treatment, and diagnosis established within previous 24 h. Neonates will be randomized to RIC (intervention) or no-RIC (control) and will continue to receive standard management of NEC. We expect to recruit and randomize 40% of eligible patients in the collaborating centers (78 patients; 39/arm) in 30 months. Bayesian methods will be used to combine uninformative prior distributions with the corresponding observed proportions from this trial to determine posterior distributions for parameters of feasibility. CONCLUSIONS: The newly established NEC consortium has generated novel data on NEC diagnosis and defined the feasibility parameters for the introduction of a novel treatment in NEC. This phase II RCT will inform a future phase III RCT to evaluate the efficacy and safety of RIC in early-stage NEC.

Fetal Meconium Peritonitis - Prenatal Findings and Postnatal Outcome: A Case Series, Systematic Review, and Meta-Analysis.

PURPOSE: To describe the postnatal outcome of fetal meconium peritonitis and identify prenatal predictors of neonatal surgery. METHODS: We retrospectively reviewed all fetuses with ultrasound findings suspicious for meconium peritonitis at a single center over a 10-year period. A systematic review and meta-analysis were then performed pooling our results with previous studies assessing prenatally diagnosed meconium peritonitis and postnatal outcome. Prenatal sonographic findings were analyzed to identify predictors for postnatal surgery. RESULTS: 34 cases suggestive of meconium peritonitis were diagnosed at our center. These were pooled with cases from 14 other studies yielding a total of 244 cases. Postnatal abdominal surgery was required in two thirds of case (66.5 %). The strongest predictor of neonatal surgery was meconium pseudocyst (OR [95 % CI] 6.75 [2.53-18.01]), followed by bowel dilation (OR [95 % CI] 4.17 [1.93-9.05]) and ascites (OR [95 % CI] 2.57 [1.07-5.24]). The most common cause of intestinal perforation and meconium peritonitis, found in 52.2 % of the cases, was small bowel atresia. Cystic fibrosis was diagnosed in 9.8 % of cases. Short-term neonatal outcomes were favorable, with a post-operative mortality rate of 8.1 % and a survival rate of 100 % in neonates not requiring surgery. CONCLUSION: Meconium pseudocysts, bowel dilation, and ascites are prenatal predictors of neonatal surgery in cases of meconium peritonitis. Fetuses with these findings should be delivered in centers with pediatric surgery services. Though the prognosis is favorable, cystic fibrosis complicates postnatal outcomes.

Mild Idiopathic Infantile Hypercalcemia-Part 1: Biochemical and Genetic Findings.

CONTEXT: Idiopathic infantile hypercalcemia (IIH), an uncommon disorder characterized by elevated serum concentrations of 1,25 dihydroxyvitamin D (1,25(OH)2D) and low parathyroid hormone (PTH) levels, may present with mild to severe hypercalcemia during the first months of life. Biallelic variants in the CYP24A1 or SLC34A1 genes are associated with severe IIH. Little is known about milder forms. OBJECTIVE: This work aims to characterize the genetic associations and biochemical profile of mild IIH. METHODS: This is a cross-sectional study including children between age 6 months and 17 years with IIH who were followed in the Calcium Clinic at the Hospital for Sick Children (SickKids), Toronto, Canada. Twenty children with mild IIH on calcium-restricted diets were evaluated. We performed a dietary assessment and analyzed biochemical measures including vitamin D metabolites and performed a stepwise molecular genetic analysis. Complementary biochemical assessments and renal ultrasounds were offered to first-degree family members of positive probands. RESULTS: The median age was 16 months. Median serum levels of calcium (2.69 mmol/L), urinary calcium:creatinine ratio (0.72 mmol/mmol), and 1,25(OH)2D (209 pmol/L) were elevated, whereas intact PTH was low normal (22.5 ng/L). Mean 1,25(OH)2D/PTH and 1,25(OH)2D/25(OH)D ratios were increased by comparison to healthy controls. Eleven individuals (55%) had renal calcification. Genetic variants were common (65%), with the majority being heterozygous variants in SLC34A1 and SLC34A3, while a minority showed variants of CYP24A1 and other genes related to hypercalciuria. CONCLUSION: The milder form of IIH has a distinctive vitamin D metabolite profile and is primarily associated with heterozygous SLC34A1 and SLC34A3 variants.

Utility of sonography for identifying metastatic cervical adenopathy in children with differentiated thyroid carcinoma at presentation.

BACKGROUND: No study has evaluated the diagnostic accuracy of sonography for the depiction of metastatic cervical adenopathy in children with differentiated thyroid carcinoma at presentation or determined which sonographic features are most useful. OBJECTIVE: To evaluate the diagnostic accuracy of sonography for identifying metastatic cervical adenopathy in children with differentiated thyroid carcinoma at presentation and to determine the most useful sonographic features. MATERIALS AND METHODS: We evaluated cervical lymph node sonography and histology in children with proven thyroid carcinoma in a 10-year period. We excluded children in whom a preoperative sonogram was not available and those who did not have surgical resection of lymph nodes. We used histology as the gold standard. On sonography, we analyzed the size, shape, echotexture and vascularity of the lymph nodes and correlated these findings with the histology. RESULTS: We reviewed sonograms and histology of resected lymph nodes in 52 children and adolescents with proven differentiated thyroid carcinoma (33 females; ages 5-18 years, mean 13.2 years). Metastatic cervical lymph node disease was proved on histology in 33/52 (64%) of our patients at presentation. Sonographic findings correctly predicted whether the nodes were histologically involved with metastatic disease in 42/52 (81%). Sensitivity of sonography was 79%, specificity 84%, positive predictive value (PPV) 90%, negative predictive value (NPV) 70% and accuracy 81%. A significant association was seen between round shape (P=0.0002), abnormal echotexture (P≤0.0001) and vascularity (P≤0.0001), and abnormal lymph node histology. Importantly, in 11/26 (47%) patients with sonographic and histologically proven abnormal nodes, the nodes were normal in size and shape and the presence of metastatic involvement was recognized sonographically only on the basis of abnormal echogenicity and vascularity. CONCLUSION: Sonography has a high accuracy, specificity and PPV for identifying metastatic cervical lymph node involvement in children with differentiated thyroid carcinoma at presentation. Most of the abnormal lymph nodes were round in shape and had abnormal echogenicity and vascularity. Importantly, this paper emphasizes that in children, nodes with histologically proven metastases from differentiated thyroid carcinoma can be normal in size and shape. In these patients the presence of metastatic involvement might be recognized sonographically only on the basis of abnormal echogenicity and vascularity.

Remote ischemic conditioning counteracts the intestinal damage of necrotizing enterocolitis by improving intestinal microcirculation.

Necrotizing enterocolitis (NEC) is a devastating disease of premature infants with high mortality rate, indicating the need for precision treatment. NEC is characterized by intestinal inflammation and ischemia, as well derangements in intestinal microcirculation. Remote ischemic conditioning (RIC) has emerged as a promising tool in protecting distant organs against ischemia-induced damage. However, the effectiveness of RIC against NEC is unknown. To address this gap, we aimed to determine the efficacy and mechanism of action of RIC in experimental NEC. NEC was induced in mouse pups between postnatal day (P) 5 and 9. RIC was applied through intermittent occlusion of hind limb blood flow. RIC, when administered in the early stages of disease progression, decreases intestinal injury and prolongs survival. The mechanism of action of RIC involves increasing intestinal perfusion through vasodilation mediated by nitric oxide and hydrogen sulfide. RIC is a viable and non-invasive treatment strategy for NEC.

The role of sonography in differentiating congenital intrinsic duodenal anomalies from midgut malrotation: emphasizing the new signs of duodenal and gastric wall thickening and hyperechogenicity.

BACKGROUND: The clinical and plain radiographic differentiation of congenital intrinsic duodenal anomalies (atresia, web, stenosis) from intestinal malrotation is not always clear. Although sonography has been documented as an important diagnostic tool in the differentiation of these two entities, its role is still not widely appreciated and it is still not universally utilized in this clinical setting. OBJECTIVE: To assess the usefulness of sonographic features of the duodenal and gastric wall in the differentiation of congenital intrinsic duodenal anomalies from midgut malrotation in a large series of neonates and to compare them with other features on abdominal radiographs, ultrasound and upper gastrointestinal series. MATERIALS AND METHODS: Using the surgical database at our tertiary pediatric hospital, we identified neonates who had surgically proven congenital intrinsic duodenal anomalies or malrotation over a period of 15 years (2000-2015). We reviewed imaging findings in both groups of neonates (blinded to the final diagnosis) with attention to the echogenicity and thickness of the wall of the duodenum and stomach, the relationship between the superior mesenteric artery and vein, the position of the third portion of the duodenum and the presence of the whirlpool sign. Findings were compared between the groups using the unpaired t-test and Fisher exact test. RESULTS: We included 107 neonates in the study, 40 with a congenital intrinsic duodenal anomaly, 49 with malrotation (36 with volvulus) and 18 with a combination of both. Duodenal and gastric wall thickening and hyperechogenicity were significantly more common in the group with a congenital intrinsic duodenal anomaly compared to those with malrotation (P<0.0001). Conversely, an abnormal relationship between the superior mesenteric artery and vein, abnormal position of the third part of the duodenum, and the whirlpool sign were significantly more common in neonates with malrotation than in those with congenital intrinsic duodenal anomalies (P<0.0001). CONCLUSION: Duodenal or gastric wall thickening, and increased wall echogenicity are helpful sonographic features in the differentiation of congenital intrinsic duodenal anomalies from malrotation. Evaluation of the duodenal and gastric wall should thus be added to the features routinely assessed on ultrasound examinations in the clinical setting of suspected duodenal obstruction in the neonate.

The role of sonography for depiction of a whirlpool sign unrelated to midgut malrotation in neonates.

BACKGROUND: The sonographic whirlpool sign of volvulus due to midgut malrotation is well recognized. However, variations of the whirlpool sign may be seen in other conditions, but this observation has received little attention in the literature. OBJECTIVE: This study presents a series of neonates with a variety of causes of congenital intestinal obstruction, all associated with a whirlpool sign (unrelated to midgut volvulus), which was correctly recognized preoperatively on sonography. We also emphasize the pivotal role of sonography in managing congenital obstruction of the intestinal tract in neonates. MATERIALS AND METHODS: This is a retrospective analysis of clinical, imaging and surgical findings in 11 neonates with congenital intestinal obstruction associated with a whirlpool sign (unrelated to midgut volvulus) that was recognized preoperatively on sonography and in whom the cause for the whirlpool was documented at surgery. RESULTS: Eleven neonates (eight male, three female) had clinical and radiographic evidence of intestinal obstruction in whom sonography depicted a whirlpool sign, which was recognized on the initial sonogram in nine and on a repeat sonogram in two. The whirlpool was located in the upper abdomen in only two, mid-abdomen in five and right lower quadrant in four. The whirlpool was only 1-2 cm in diameter. An upper gastrointestinal series in three neonates failed to depict the cause of obstruction. Contrast enema in three cases had findings suggesting the site of obstruction was in the ileum but none depicted the exact cause of the obstruction. At surgery, the whirlpool sign correlated with a segmental volvulus of the small intestine in eight neonates and with the coiled distal small intestine associated with apple-peel atresia in the other three. CONCLUSION: This study illustrates neonates in whom a whirlpool sign (unrelated to midgut volvulus) was correctly recognized on sonography before surgery. Sonography proved more useful than an upper gastrointestinal series or contrast enema in depicting the exact cause of the obstruction. Pediatric radiologists must make the effort to search throughout the entire abdomen and pelvis for a small whirlpool sign on sonography, even in the absence of midgut malrotation, in neonates with congenital intestinal obstruction. Its recognition preoperatively will facilitate a rapid diagnosis and will obviate the necessity for contrast examinations of the gastrointestinal tract, which require ionizing radiation.

Meconium peritonitis: the role of postnatal radiographic and sonographic findings in predicting the need for surgery.

BACKGROUND: The role of imaging in meconium peritonitis is not limited to establishing a diagnosis; rather, it might also be helpful in determining which neonates require surgery. However, few data in the literature correlate the postnatal radiographic and sonographic findings with the need for surgery. OBJECTIVE: To compare the role of postnatal radiographic and sonographic findings in predicting the need for surgery in neonates with meconium peritonitis. MATERIALS AND METHODS: We conducted a retrospective analysis of clinical, imaging and surgical findings in all neonates with meconium peritonitis in the period 1999-2014. We divided the children into operative or non-operative groups and then correlated each group with the presence or absence of the following findings on both the radiographs and sonograms: peritoneal calcification, meconium pseudocyst, intestinal obstruction, volvulus, ascites and pneumoperitoneum. RESULTS: Thirty-seven neonates (22 males, 15 females) had meconium peritonitis in this period, of whom 23 (62%) required surgery and 14 (38%) were successfully treated non-surgically. None had an antenatal infection and three had cystic fibrosis (8%). Bowel obstruction identified on radiography (12/23, P=0.01) and sonography (9/23, P=0.04) and ascites identified with sonography (7/23, P=0.01) were associated with the need for surgical intervention. The presence of pneumoperitoneum and volvulus were also associated with surgical intervention. There was no significant statistical difference in the number of neonates with diffuse peritoneal calcification who were treated operatively or non-operatively. Four (33%) of the 12 neonates with meconium pseudocysts were successfully treated non-operatively. CONCLUSION: Imaging findings that predicted the need for surgery were intestinal obstruction, ascites, volvulus and pneumoperitoneum. Neonates with meconium pseudocysts did not require surgery if they were not associated with the described findings. The findings in our patients also indicate that those with diffuse peritoneal calcification as an isolated finding can be successfully treated non-operatively.

Nutrient enrichment of human milk with human and bovine milk-based fortifiers for infants born weighing <1250 g: a randomized clinical trial.

Background: Human milk-based fortifiers (HMBFs) are being adopted in neonatal care to enrich the nutrients in human milk for very low birth weight (VLBW) infants despite being costly and there being limited efficacy data. No randomized clinical trial has evaluated the use of HMBF compared with bovine milk-based fortifiers (BMBFs) in the absence of formula feeding. Objective: To determine if HMBF compared with BMBF for routine nutrient enrichment of human milk improves feeding tolerance, reduces morbidity, reduces fecal calprotectin (a measure of gut inflammation), and supports the growth of infants <1250 g. Design: In this blinded randomized clinical trial, infants born weighing <1250 g were recruited from neonatal units in Ontario, Canada between August 2014 and November 2015. The infants were fed mother's milk and donor milk as required. Fortification commenced at 100 mL/kg per day of HMBF (0.81 kcal/mL) or BMBF (0.72 kcal/mL) and advanced at 140 mL/kg per day to 0.88 and 0.78 kcal/mL, respectively. The primary outcome was percentage of infants with a feeding interruption for ≥12 h or a >50% reduction in feeding volume. Secondary outcomes included a dichotomous mortality and morbidity index (i.e., affirmative for any one of death, late-onset sepsis, necrotizing enterocolitis, chronic lung disease, or severe retinopathy of prematurity), fecal calprotectin, and growth. Results: Of 232 eligible infants, 127 (54.7%) were randomized (n = 64 HMBF, n = 63 BMBF). Mean ± SD birth weight and gestational age of infants were 888 ± 201 g and 27.7 ± 2.5 wk, respectively. No statistically significant differences were identified in feeding interruptions [17/64 HMBF, 20/61 BMBF; unadjusted risk difference: -6.2% (95% CI: -22.2%, 9.8%)]. There was no statistically significant difference in the mortality and morbidity index (48.4% HMBF, 49.2% BMBF, adjusted P = 0.76), changes in fecal calprotectin, or growth z scores. Conclusions: Among infants born weighing <1250 g and exclusively fed human milk, the use of HMBF did not improve feeding tolerance or reduce mortality and morbidity compared with BMBF. This trial was registered at clinicaltrials.gov as NCT02137473.

Value of abdominal ultrasound in management of necrotizing enterocolitis: a systematic review and meta-analysis.

PURPOSE: Necrotizing enterocolitis (NEC) remains a life-threatening disease among infants in the NICU. Early diagnosis and careful monitoring are essential to improve outcomes. Abdominal ultrasound (AUS) seems a promising addition to current diagnostic modalities, but its clinical utility is uncertain. The aim of this study was to identify AUS features associated with definite NEC (i.e. Bell stage ≥ II), failed medical treatment, surgery, and death. METHODS: Embase, MEDLINE, Web of Science and CINAHL databases were searched for studies that addressed any NEC-related AUS feature in relation to any of the four outcomes. After critical appraisal of relevant study methods, meta-analyses were conducted using a random-effect model. RESULTS: 15 out of 1215 studies were included. All AUS features had sensitivities below 70% and specificities largely above 80% for diagnosing definite NEC; several AUS features were significantly associated with failed medical treatment and surgery. Substantial heterogeneity, poor reporting quality and uncertain risk of bias were found. CONCLUSIONS: While clear associations of AUS features with failed medical treatment exist and AUS may detect definite NEC, substantial heterogeneity, poor reporting quality and an uncertain risk of bias impair the use of AUS for clinical decision making. A prospective, well-designed validation study is needed.

Utility of adult-based ultrasound malignancy risk stratifications in pediatric thyroid nodules.

BACKGROUND: Individual ultrasound (US) features have limited ability to distinguish benign from malignant thyroid nodules. Adult-based systems have been developed to integrate the sonographic features in an effort to improve diagnostic accuracy. None, however, has been validated in children, in whom the likelihood of malignancy is 2-5 times higher than adults. OBJECTIVE: To assess the performance of two adult-based sonographic (US) stratification methods for assessment of thyroid nodules in children. MATERIALS AND METHODS: This retrospective study comprised 124 children who underwent thyroid US. Three radiologists reviewed the US data using the American Thyroid Association (ATA) and the Thyroid Image Reporting and Data System (TI-RADS). Radiologists' accuracy and agreement was assessed. The reference standard was histopathology/cytology or 2-year follow-up of clinical outcome for nonoperative cases. RESULTS: We assessed 71 benign and 52 malignant nodules and excluded 1 nodule. Using the ATA pattern descriptions, 80% of malignant nodules were classified as "high" 36/52 (69%) or "intermediate" 6/52 (11%) likelihood of malignancy. A total of 20/71 (28%) benign nodules were also classified within these two categories. Using the TI-RADS, malignant nodules were classified as 2, 3, 4a, 4b, 4c and 5, with rate of malignancy of 0%, 0%, 7/52 (13.5%), 7/52 (13.5%), 32/52 (61.5%) and 6/52 (11.5%), respectively. Benign nodules were also classified in the 4a (26/71; 36.6%), 4b (17/71; 24%), 4c (14/71; 19.7%) and 5 (1/71; 1.4%) categories. The positive and negative predictive values were 68.0% and 87.5% for ATA, and 71.7% and 80.0% for TI-RADS. CONCLUSION: We validated the use of ATA and TI-RADS methods in children and showed that they have test characteristics similar to those in adults, although neither is independently sufficient to discriminate nodules' likelihood of malignancy.

Intraventricular hemorrhage in term neonates with hypoxic-ischemic encephalopathy: a comparison study between neonates treated with and without hypothermia.

BACKGROUND: To retrospectively determine the prevalence of intraventricular hemorrhage (IVH) in term neonates with hypoxic-ischemic encephalopathy (HIE) using head ultrasound (HUS) and MRI, and to compare the incidence of IVH in term babies with HIE treated by therapeutic hypothermia versus those managed conventionally. METHODS: A total of 61 term neonates from two institutions were diagnosed with HIE shortly after birth. Thirty infants from one institution were treated with whole body hypothermia. These infants had to satisfy the entry criteria for the neonatal hypothermia protocol of the institution. Thirty-one neonates underwent conventional treatment at the second institution. At that time, hypothermia was not yet a standard of care at that institution. All the neonates underwent HUS in their first 23 days of life. The 54 survivors also underwent MRI. The imaging studies were all reviewed for IVH. RESULTS: Amongst the 30 babies, who received whole body hypothermia, there were 18 males and 12 females, the mean birth weight was 3.5 kg (2.5 to 5.2 kg), and the HUS study was performed within 14.8 to 41 hours of life. The group of 31 infants treated conventionally was comprised of 12 boys and 19 girls, the infants had an average birth weight of 3.3 kg (2.3 to 4.2 kg), and they underwent HUS 1 to 23 days after birth, with only five children being older than 1 week at the time of the imaging studies. Four of the 61 infants (7%) were diagnosed with IVH on HUS. Three were confirmed with MRI. The fourth case showed a bilateral enlarged choroid plexus on HUS, but IVH could not be confirmed with MRI, as the infant did not survive. In the group of neonates treated with hypothermia, there were three cases (10%) of IVH, whereas in the group managed conventionally, IVH occurred in one infant (3%). CONCLUSIONS: Our study shows that IVH remains uncommon in term infants with HIE. IVH was more prevalent in the group treated with hypothermia.

Effect of Supplemental Donor Human Milk Compared With Preterm Formula on Neurodevelopment of Very Low-Birth-Weight Infants at 18 Months: A Randomized Clinical Trial.

Importance: For many very low-birth-weight (VLBW) infants, there is insufficient mother's milk, and a supplement of pasteurized donor human milk or preterm formula is required. Awareness of the benefits of mother's milk has led to an increase in use of donor milk, despite limited data evaluating its efficacy. Objective: To determine if nutrient-enriched donor milk compared with formula, as a supplement to mother's milk, reduces neonatal morbidity, supports growth, and improves neurodevelopment in VLBW infants. Design, Setting, and Participants: In this pragmatic, double-blind, randomized trial, VLBW infants were recruited from 4 neonatal units in Ontario, Canada, within 96 hours of birth between October 2010 and December 2012. Follow-up was completed in July 2015. Interventions: Infants were fed either donor milk or formula for 90 days or to discharge when mother's milk was unavailable. Main Outcomes and Measures: The primary outcome was the cognitive composite score on the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) at 18 months' corrected age (standardized mean, 100 [SD, 15]; minimal clinically important difference, 5 points). Secondary outcomes included Bayley-III language and motor composite scores, growth, and a dichotomous mortality and morbidity index. Results: Of 840 eligible infants, 363 (43.2%) were randomized (181 to donor milk and 182 to preterm formula); of survivors, 299 (92%) had neurodevelopment assessed. Mean birth weight and gestational age of infants was 996 (SD, 272) g and 27.7 (2.6) weeks, respectively, and 195 (53.7%) were male. No statistically significant differences in mean Bayley-III cognitive composite score (adjusted scores, 92.9 in donor milk group vs 94.5 in formula group; fully adjusted mean difference, -2.0 [95% CI, -5.8 to 1.8]), language composite score (adjusted scores, 87.3 in donor milk group vs 90.3 in formula group; fully adjusted mean difference, -3.1 [95% CI, -7.5 to 1.3]), or motor composite score (adjusted scores, 91.8 in donor milk group vs 94.0 in formula group; fully adjusted mean difference, -3.7 [95% CI, -7.4 to 0.09]) were observed between groups. There was no statistically significant difference in infants positive for the mortality and morbidity index (43% in donor milk group, 40% in formula group) or changes in growth z scores. Conclusions and Relevance: Among VLBW infants, use of supplemental donor milk compared with formula did not improve neurodevelopment at 18 months' corrected age. If donor milk is used in settings with high provision of mother's milk, this outcome should not be considered a treatment goal. Trial Registration: isrctn.org Identifier: ISRCTN35317141.

Sonographic Bands of Hypoechogenicity in the Spleen in Children: Zebra Spleen.

OBJECTIVE: Zebra spleen is the normal pattern of splenic enhancement during the arterial phase of CT and MRI and is attributed to different flow rates. The purpose of this study was to describe the appearance and occurrence of bands of hypoechogenicity in the spleen on unenhanced sonograms of children with no splenic abnormalities. MATERIALS AND METHODS: We reviewed 100 abdominal ultrasound studies to evaluate the ultrasound characteristics of the spleen. Demographic data were collected for all patients. RESULTS: Homogeneous echogenicity of the spleen was found in 92 children. Heterogeneous echogenicity was present in eight. Three of the eight had discrete macronodules due to known splenic disease. The other five had bands of hypoechogenicity. These five had no known splenic disease, but one had mild splenomegaly of unknown cause. CONCLUSION: The pattern of hypoechoic bands occurred in 5% of our series. This pattern cannot be explained simply by different flow rates and probably reflects different structural components of the parenchyma. At ultrasound this pattern should be considered a normal finding that may simulate a splenic mass.