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OBJECTIVES Four-hour gastric emptying scintigraphy (GES) is the recommended method to identify both adult and childhood gastroparesis (GP). Previous pediatric studies have, however, not used this standard. We sought to determine the characteristics and outcomes of children versus adolescents with GP using the 4-hour GES evaluation. METHODS We performed a retrospective chart review of pediatric patients diagnosed with GP by 4-hour GES (>10% retention at 4 hours). Demographics, body mass index, GP-related symptoms, comorbidities, etiologies, therapies (eg, medications), healthcare utilization, and response to therapy were captured systematically. Symptoms were compared from the initial versus last gastroenterology visit. Outcomes were categorized as no improvement; improvement (resolution of at least 1 symptom while remaining on therapy); and complete resolution of symptoms. RESULTS A total of 239 subjects (12.1 ± 4.1 years [mean ± standard deviation], 70% girls) were included. The identified characteristics of childhood GP were broad with idiopathic GP being the most common etiology. Outcomes over a median of 22 months (25%-75%: 9.0-45.5 months) were 34.8% no improvement, 34.8% some improvement, and 30.3% with complete symptom resolution. Compared to younger children, adolescents had a higher female predominance (P

Objective The aim of the study was to examine the ability of overreading of computed tomography (CT) and right lower quadrant ultrasound (RLQ US) to diagnose appendicitis for children with suspected appendicitis with equivocal CTs at community hospitals. Methods This was a retrospective chart review of all children transferred to a children's hospital from community emergency departments with suspected appendicitis over 2 years for whom both CT and RLQ US were performed. Results One hundred eighty-four children were included with a median age of 10.8 years, and 57.6% were female. Community hospitals documented that CTs were equivocal for appendicitis in 110 (59.8%), positive in 63 (34.2%), and negative in 11 (6.0%). Ninety-seven CTs (88.1%) designated equivocal at community hospitals were later deemed interpretable by pediatric radiologists: 21 (19.1%) as appendicitis and 76 (69.1%) as normal. In 13 children (11.8%), both the community and children's hospital CT interpretations were equivocal. In equivocal cases, RLQ US was consistent with appendicitis in 6 (46.2%), normal in 5 (41.7%), and nondiagnostic in 2. κ value between CT interpretations at community versus children's hospital was 0.13 (95% confidence interval, 0.05-0.22), and κ value between CT interpretation at the children's hospital and RLQ US was 0.59 (95% confidence interval, 0.48-0.70). Conclusions Most CTs deemed equivocal for appendicitis at community hospitals were interpretable by pediatric radiologists. In a few children for whom CTs were designated nondiagnostic, RLQ US provided a definitive diagnosis in almost 90% of cases. The first step in evaluation of children with suspected appendicitis for whom outside CTs are deemed equivocal should be to have the study reinterpreted by a pediatric radiologist.

BACKGROUND: Physicians often obtain a routine renal bladder ultrasound (RBUS) for young children with a first febrile urinary tract infection (UTI). However, few children are diagnosed with serious anatomic anomalies, and opportunity may exist to take a focused approach to ultrasonography. We aimed to identify characteristics of the child, prenatal ultrasound (PNUS), and illness that could be used to predict an abnormal RBUS and measure the impact of RBUS on management. METHODS: We conducted a single-center prospective cohort study of hospitalized children 0 to 24 months of age with a first febrile UTI from October 1, 2016, to December 23, 2018. Independent variables included characteristics of the child, PNUS, and illness. The primary outcome, abnormal RBUS, was defined through consensus of a multidisciplinary team on the severity of ultrasound findings important to identify during a first UTI. RESULTS: A total of 211 children were included; the median age was 1.0 month (interquartile range 0–2), and 55% were uncircumcised boys. All mothers had a PNUS with 10% being abnormal. Escherichia coli was the pathogen in 85% of UTIs, 20% (n = 39 of 197) had bacteremia, and 7% required intensive care. Abnormal RBUS was found in 36% (n = 76 of 211) of children; of these, 47% (n = 36 of 76) had moderately severe findings and 53% (n = 40 of 76) had severe findings. No significant difference in clinical characteristics was seen among children with and without an abnormal RBUS. One child had Foley catheter placement, and 33% received voiding cystourethrograms, 15% antibiotic prophylaxis, and 16% subspecialty referrals. CONCLUSIONS: No clinical predictors were identified to support a focused approach to RBUS examinations. Future studies should investigate the optimal timing for RBUS.

Purpose Clinical prediction of disease severity is important as one considers nonoperative management of simple appendicitis. This study assesses the accuracy of surgeons' prediction of appendicitis severity. Methods From February to August 2016, pediatric surgeons at a single institution were asked to predict whether patients had simple or complex appendicitis preoperatively based on clinical data, imaging, and general assessment. Receiver operating characteristic curves were generated to determine area under the curve (AUC) and optimal cutoff points of clinical findings for diagnosing simple appendicitis. Outcomes included sensitivity and specificity of variables to identify simple appendicitis. Predictions were compared to operative findings using χ2. A p-value Results Of 125 cases (median age 9 years [IQR 7–13], 58% male), simple appendicitis was predicted in 77 (62%) and complex appendicitis in 48 (38%). Predictions were accurate in 59 (77%) simple cases and 45 (94%) complex cases. Although surgeon prediction was more accurate than individual imaging or clinical findings and was highly sensitive (95%) for diagnosing simple appendicitis, specificity was only 71%. Lower WBC ( Conclusion While surgeon prediction of simple appendicitis is more accurate than ultrasound or clinical data alone, diagnostic accuracy is still limited. Type of study Prospective survey. Level of evidence II

The human disease fibrodysplasia ossificans progressiva (FOP) is a rare and highly disabling disorder of extensive heterotopic bone growth that is caused by a point mutation (R206H) in the activation domain of Alk2, a BMP (bone morphogenic protein) type 1 receptor. The mutation leads to extensive BMP-signaling induced by Activin A, which is normally an antagonist for wildtype receptors, resulting in excessive and uncontrolled bone formation. Here, we studied the effects of Pasteurella multocida toxin (PMT), which activates osteoclasts and inhibits osteoblast activity, in C2C12 myoblasts expressing the mutant Alk2(R206H) receptor as model of FOP. In our study, we mainly used alkaline phosphatase (ALP) activity as marker to determine osteoblast differentiation. BMP-4 stimulated an increase in ALP activity in C2C12-Alk2wt and C2C12-Alk2(R206H) cells. By contrast, Activin A only induced ALP activity in C2C12-Alk2(R206H) cells. In both cases, PMT acted as a potent inhibitor of ALP activity. PMT-induced inhibition of ALP activity was paralleled by a constitutive activation of the heterotrimeric Gq protein. Expression of a permanently active Gαq blocked Activin A/Alk2(R206H)-dependent increase in ALP activity. Inactivation of Gq by specific inhibitor FR900359 blocked the PMT effect. Similarly, canonical second messengers and effectors of Gαq (e.g. ionophore A23187-induced increase in intracellular Ca2+ and activation of PKC by PMA (phorbol 12-myristate 13-acetate)) inhibited Alk2(R206H)-mediated induction of ALP activity. Notably, Activin A-induced increase in ALP activity in C2C12-Alk2(R206H) cells was also inhibited by stimulation of the α1A-adrenoceptor, which couples to Gαq, by phenylephrine. PMT did not alter tail phosphorylation of the major downstream effectors of the Alk2 receptor, Smad1/5/9; neither did the toxin affect nuclear translocation of the Smad-complex. However, PMT diminished BMP responsive element-induced gene expression. The data indicate that PMT potently inhibits the induction of osteoblast markers in a FOP model via activation of G proteins. Moreover, our findings indicate that activation of G protein-coupled receptors and of G protein signaling might be a rationale for pharmacological therapy of FOP.

The main objective of this paper is to present a new and cost-effective Information and Communication Technology (ICT) tool that can lead to efficient energy management in buildings and optimal operation of electricity networks with increased share of Renewable Energy Sources (RES) and Electric Vehicles (EVs). The new ICT infrastructure is based on the Digital Audio Broadcasting (DAB) standard and its interoperability with smart metering technology, Intelligent Transportation Systems (ITS) and Building Automation Systems (BAS). The main idea involves the attachment of a DAB receiver to electric devices (from small household appliances up to EVs and solar systems and other RES). In this paper, the DAB protocol is described, enabling high cyber-physical security. Moreover, the results of addressing a thermostatically-controlled load using DAB-signaling in Switzerland are also presented. The next steps envisioned are i) the validation of the final protocol version and of the DAB receivers for various electric appliances and DR schemes and, ii) demonstration of the new technology in real-life cases through the National DAB broadcaster in Greece.

Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy in children and adolescents. Infrequently, children with PTC may present with or develop disease not amenable to surgery or radioactive iodine (RAI), and systemic therapy may be an option. Lenvatinib is an oral tyrosine kinase inhibitor that is approved by the Food and Drug Administration for the treatment of adults with locally recurrent or metastatic, progressive, RAI-refractory well-differentiated thyroid carcinoma. The effect of lenvatinib in children with PTC has not been reported.Three children with metastatic PTC not amenable or refractory to RAI who responded to lenvatinib are reported. All of them developed respiratory distress requiring oxygen caused by extensive bilateral metastatic pulmonary disease. The first patient is a 14-year-old female who was initially treated with sorafenib for extensive PTC not amenable to upfront surgery or RAI. She had progressive pulmonary disease after five months, and was subsequently treated with oral lenvatinib (14 mg/mThree pediatric patients are reported with metastatic PTC not amenable or refractory to RAI who achieved a response on lenvatinib.Lenvatinib therapy is well tolerated and demonstrated clinical activity in children with advanced PTC. Lenvatinib should be considered in children with PTC that is refractory or not amenable to conventional management.

Ileocolic intussusception occurs when the terminal ileum “telescopes” into the colon. We observed that ileocolic intussusception lengths are similar regardless of location in the colon. To examine the uniformity of ileocolic intussusception length and its relationship to colon location, symptom duration and reducibility. We retrospectively reviewed ultrasound-diagnosed pediatric ileocolic intussusceptions initially treated with pneumatic reduction at the Mayo Clinic or Texas Children’s Hospital. We recorded demographic, imaging and surgical findings including age, gender, symptom duration, location of the ileocolic intussusception, reducibility with air enema and, if fluoroscopically irreducible, surgical findings. We identified 119 ileocolic intussusceptions (64% boys), with 81% in the right colon. There was no significant relationship between ileocolic intussusception length and colon location (P=0.15), nor ileocolic intussusception length and symptom duration (P=0.36). Ileocolic intussusceptions were more distal with increasing symptom duration (P=0.016). Successful reductions were unrelated to symptom duration (P=0.84) but were more likely with proximal versus distal locations (P=0.02). Ileocolic intussusception lengths are relatively uniform regardless of location along the course of the colon where they present. Our findings suggest that most of the apparent distal propagation of ileocolic intussusceptions is not caused by increasing telescoping of small bowel across the ileocecal valve but rather by foreshortening of the right colon. This implies poor cecal fixation and confirms fluoroscopic and surgical observations of cecal displacement from the right lower quadrant with ileocolic intussusceptions. The movement of the leading edge of the ileocolic intussusception during reduction is first due to “relocating” the cecum into the right lower quadrant after which the reduction of small bowel back across the ileocecal valve then occurs.

In studies of diagnostic performance that fail to detect a statistically significant difference between compared techniques, investigators often declare evidence of equivalence or similarity without having actually tested that assertion due to incorrect methodology or insufficient statistical power. The purpose of our investigation is to measure the prevalence of unfounded assertions of equivalence or similarity in comparison studies presented at the International Pediatric Radiology (IPR) meeting of 2016 and promote awareness of this fallacy of inference to the pediatric radiology community. Two pediatric radiologists independently reviewed the methodology and reporting quality of the 194 scientific paper abstracts from the 2016 IPR meeting. All comparison studies were identified and those failing to detect a statistically significance difference and making a claim of equivalence or similarity in the results or conclusion were assessed for a description of the study design type, statistical power and sample size estimator calculation. Of 194 scientific paper abstracts, 112 (58%) were comparison studies. Of these, 36/112 (32%) made unfounded inferences of equivalence or similarity in diagnostic imaging performance. No study had an equivalence or non-inferiority design. No abstract specified the statistical power of the study, and only one abstract acknowledged a small sample size as a limitation in detecting a statistically significant difference. Inadequate reporting and unfounded inferences of equivalence or similarity were common in diagnostic performance comparison studies presented at IPR 2016. Failure to recognize these limitations could have adverse consequences by leading to the adoption of unvalidated imaging techniques.

Glenoid version angles are measured to objectively follow changes related to glenohumeral dysplasia in the setting of brachial plexus birth palsy. Measuring glenoid version on cross-sectional imaging was initially described by Friedman et al. in 1992. Recent literature for non-dysplastic shoulders advocates time-consuming reconstructions and reformations for an accurate assessment of glenoid version. To compare Friedman’s original method for measuring glenoid version to a novel technique we developed (“modified Friedman”) with the reference standard of true axial reformations. With institutional review board approval, we retrospectively examined 30 normal and dysplastic shoulders obtained from magnetic resonance imaging examinations of 30 patients with an established diagnosis of brachial plexus birth palsy between January 2012 and September 2017. Four pediatric radiologists performed glenoid version measurements using Friedman’s method, the modified Friedman method and a previously described true axial reformation method. The modified Friedman technique better accounts for scapular positioning by selecting a reference point related to the acromion-scapular body interface. Inter-rater reliability and inter-method agreement were assessed using intraclass correlation, paired t-tests and mixed linear model analysis. Equivalence tests between methods were performed per reader. Glenoid version measurements were significantly different when comparing Friedman’s method to true axial reformations in normal (-10.8±5.7° [mean±standard deviation] vs. -8.8±5.3°; P≤0.001) and dysplastic shoulders (-34.6±17.7° vs. -28.1±17.5°; P≤0.001). Glenoid version measurements were not significantly different when comparing the modified Friedman’s method to true axial reformations in normal (-6.3±5.8° vs. -8.8±5.3°; P=0.06) and dysplastic shoulders (-29.0±18.3° vs. -28.1±17.5°; P=0.06). Friedman’s method was not equivalent to true axial reformations for measurements in dysplastic shoulders for all readers (P=0.68, 0.81, 0.86, 0.99); the modified Friedman method was equivalent to of true axial reformations for measurements in dysplastic shoulders for 3 of 4 readers (P≤0.001, P≤0.001, P≤0.001, P=0.10). In glenohumeral dysplasia, the modified Friedman method and post-processed true axial reformations provide statistically similar and reproducible values. We propose that our modified Friedman technique can be performed in lieu of post-processed true axial reformations to generate glenoid version measurements.

OBJECTIVES Appendicitis is the most common surgical emergency encountered in the pediatric emergency department (ED). We analyzed the time course of children evaluated for suspected appendicitis in relation to implementation of a risk-stratified ultrasound scoring system and structured reporting template (Appy-Score). METHODS In July 2013, a 6-level ultrasound (US)-based appendicitis scoring system was developed and implemented. The records of children (age ≤18 years) who underwent limited abdominal US exams for suspected appendicitis at a large academic pediatric ED were reviewed retrospectively. Time periods evaluated were from January 1 to April 1, 2013 (before implementation of the US scoring system, "PRE") and July 1 to October 1, 2013 (after implementation of the US scoring system, "POST"). Times are presented as medians with interquartile range. RESULTS A total of 926 children were included (median age, 9.5 years [range, 0.1-18 years]; 49% female). Four hundred eighty-one patients were evaluated PRE and 445 POST. When comparing the 2 groups, there were no differences in the PRE and POST periods with regard to time from US ordered to first read (102 vs 112 minutes, P = 0.30), US ordered to disposition (215 vs 208 minutes, P = 0.40) and operating room posting (121 vs 122 minutes, P = 0.59), and overall ED stay (329 vs 333 minutes, P = 0.39). CONCLUSIONS The development of a radiographic appendicitis score, although allowing for a standardized reporting method, did not significantly alter the ED process flow for evaluation of appendicitis. This reflects the complexities in ED throughput and reveals the need for additional factors to change to improve patient flow.

Intussusception, a common cause of bowel obstruction in young children, is primarily treated with air enema reduction. There is little literature comparing the safety and efficacy of air reduction without or with a rectal balloon. To determine the safety and efficacy of a rectal balloon seal in air enema reduction. We retrospectively reviewed the records of children who underwent air reduction for ileocolic or ileo-ileocolic intussusception over an 8-year period. We sorted data from 566 children according to whether a rectal balloon was used in the reduction, and further sorted them by type and experience level of the practitioner. Using logistic regression analyses, we identified risk factors for iatrogenic bowel perforation or failed reduction. Significant associations with bowel perforation included balloon use (P=0.038), age

Rationale and Objectives For imaging pediatric appendicitis, ultrasonography (US) is preferred because of its lack of ionizing radiation, but is limited by operator dependence. This study investigates the US diagnostic performance during night shifts covered by radiology trainees compared to day shifts covered by attending radiologists. Materials and Methods Appy-Scores (1 = completely visualized normal appendix; 2 = partially visualized normal appendix; 3 = nonvisualized appendix with no inflammatory changes in the expected region of the appendix; 4 = equivocal; 5a = nonperforated appendicitis; 5b = perforated appendicitis) from 2935 US examinations (2161:774, day-to-night) from July 2013 to 2014 were correlated with the intraoperative diagnoses and the clinical follow-up. The diagnostic performance of trainees and attendings was compared with Fisher exact test. Interobserver agreement was measured by Cohen kappa coefficient. Results Appendicitis prevalence was 25.3% (day) and 22.5% (night). Sensitivity, specificity, accuracy, negative predictive value, and positive predictive vale were 94.0%, 93.7%, 93.8%, 97.9%, and 83.4% during the day and 92.0%, 91.2%, 91.3%, 97.5%, and 75.2% at night. Specificity (P = .048) and positive predictive value (P = .011) differed, with more false positives at night (7%) than during the day (4.7%). Trainee and attending agreement was high (k = 0.995), with Appy-Scores of 1, 4, and 5a most frequently discordant. Conclusions US has a high diagnostic performance and interobserver agreement for pediatric appendicitis when interpreted by radiology trainees during night shifts or attending radiologists during day shifts. However, lower specificity and positive predictive value at night warrants a thorough trainee education to avoid false-positive examinations.

Two-pore channels (TPCs) are localized in endo-lysosomal compartments and assumed to play an important role for vesicular fusion and endosomal trafficking. Recently, it has been shown that both TPC1 and 2 were required for host cell entry and pathogenicity of Ebola viruses. Here, we investigate the cellular function of TPC1 using protein toxins as model substrates for distinct endosomal processing routes. Toxin uptake and activation through early endosomes but not processing through other compartments were reduced in TPC1 knockout cells. Detailed co-localization studies with subcellular markers confirmed predominant localization of TPC1 to early and recycling endosomes. Proteomic analysis of native TPC1 channels finally identified direct interaction with a distinct set of syntaxins involved in fusion of intracellular vesicles. Together, our results demonstrate a general role of TPC1 for uptake and processing of proteins in early and recycling endosomes, likely by providing high local Ca2+ concentrations required for SNARE-mediated vesicle fusion.

Purpose To prospectively evaluate the diagnostic performance of ultrasonography (US) for differentiating perforated from nonperforated pediatric appendicitis and to investigate the association between specific US findings and perforation. Materials and Methods This HIPAA-compliant study had institutional review board approval, and the need for informed consent was waived. All abdominal US studies performed for suspected pediatric appendicitis at one institution from July 1, 2013, to July 9, 2014, were examined prospectively. US studies were reported by using a risk-stratified scoring system (where a score of 1 indicated a normal appendix; a score of 2, an incompletely visualized normal appendix; a score of 3, a nonvisualized appendix; a score of 4, equivocal; a score of 5a, nonperforated appendicitis; and a score of 5b, perforated appendicitis). The diagnostic performance of US studies designated 5a and 5b was calculated. The following US findings were correlated with perforation at multivariate analysis: maximum appendiceal diameter, wall thickness, loss of mural stratification, hyperemia, periappendiceal fat inflammation, periappendiceal fluid, lumen contents, and appendicolith presence. The number of symptomatic days prior to presentation was recorded. Surgical diagnosis and clinical follow-up served as reference standards. Results A total of 577 patients with a diagnosis of appendicitis at US met the study criteria (468 with a score of 5a; 109 with a score of 5b). Appendicitis was correctly identified in 573 (99.3%) of 577 patients. US performance in the detection of perforated appendicitis (5b) was as follows: a sensitivity of 44.0% (80 of 182), a specificity of 93.1% (364 of 391), a positive predictive value of 74.8% (80 of 107), and a negative predictive value of 78.1% (364 of 466). Statistically significant associations with perforated appendicitis were longer duration of symptoms (odds ratio [OR] = 1.46, P < .0001), increased maximum diameter (OR = 1.29, P < .0001), simple periappendiceal fluid (OR = 2.08, P = .002), complex periappendiceal fluid (OR = 18.5, P < .0001), fluid-filled lumen (OR = 0.34, P = .002), and appendicolith (OR = 1.67, P = .02). Conclusion US is highly specific but nonsensitive for perforated pediatric appendicitis. Several US findings are significantly associated with perforation, especially the presence of complex periappendiceal fluid. © RSNA, 2016.

Allogeneic hematopoietic stem cell transplant (HSCT) for relapsed pediatric non-Hodgkin lymphoma (NHL) is often reserved for patients with certain NHL subtypes or high-risk disease whereas the remainder receive autologous HSCT. Given the aggressive nature of pediatric NHL, we performed allogeneic HSCTs for all patients regardless of disease risk. We report overall survival (OS) and prognostic variables in 36 pediatric patients who underwent allogeneic HSCT between 1998 and 2016. OS at 3 years was 67%. The 3-year OS varied based on NHL subtype: 100% for anaplastic large cell lymphoma (n = 14), 63% for diffuse large B-cell lymphoma (n = 8), 17% for lymphoblastic lymphoma (LL; n = 9) and 80% for other subtypes combined (n = 5). Disease status influenced outcome with 3-year OS of 100% for patients in complete remission (n = 15), 59% with partial remission (PR; n = 17), and 0% with progressive/stable disease (n = 3) (P = .004). Of the 17 patients in PR, all 6 with LL died of relapsed disease, whereas the other 11 attained remission after HSCT and remained disease-free. The cumulative incidence of relapse after HSCT for LL was 78% compared with 15% for all other NHL subtypes combined (P < .0001). Cumulative incidence of nonrelapse mortality (NRM) was low in our cohort at 6%. Hence, allogeneic HSCT is a well-tolerated and useful therapeutic option with low rates of NRM and relapse for all NHL subtypes except LL with active disease at HSCT.

The main objective of this paper is to present a DAB protocol and a DAB grid agent prototype, as essential parts of a grid ancillary services operational model. The decentralized, small electric loads (electric vehicles, household-appliances, batteries, prosumers), clustered properly by aggregators are equipped in large amounts with the so called “grid-agents”. A grid-agent is a cost-effective, low-power, smart electric control unit consisting of a DAB+ receiver with embedded circuits for local grid voltage and frequency measurements and a microcontroller running algorithms for flexible load control. The grid-agent will optimize the electricity demand with respect to the grid status and/or to external commands received via DAB+. Moreover, especially suited for Transmission System Operators (TSOs), multi-load power facilities that are controlled by energy management systems through specific standards (e.g. KNX for hotels, Modbus for the industrial sector, etc) and even Renewable Energy Sources (RES) Distributed Generators (DGs) are equipped with a single DAB+ grid-agent.

Objective Compare the cost of placing tunneled femoral central lines in the interventional radiology suite to portable bedside placement using time-driven activity-based costing. Methods Detailed process maps were created using information generated from interviews with frontline staff, direct shadowing of patient procedures (19 patients—8 in-suite, 11 portable; patient age 4 days to 37 months; 6 males, 13 females), and electronic medical record review (80 patients—44 in-suite, 36 portable; patient age 1 day to 20 months; 42 males, 38 females) who underwent a tunneled femoral central line placement at a tertiary care pediatric hospital from January 1, 2018, to June 30, 2018. Procedures were conducted in-suite using fluoroscopy guidance or portably at the patient’s bedside using ultrasound. Capacity cost rates for each resource in the process maps were calculated for personnel, equipment, facilities, and supply costs. Costs for each process step were then calculated by multiplying the capacity cost rate by the mean duration of each step. Stepwise costs were summed for the entire process to generate a cost for each tunneled femoral central line placement pathway. Results Total pathway time for tunneled femoral central lines placement in-suite was 123 to 134 min (nonsedated) and 120 to 131 min (sedated) for a cost of $923 to $990 and $1,262 to $1,386, respectively. Total pathway time for tunneled femoral central lines placed portably were 117 to 119 min (nonsedated) and 115 to 147 min (sedated) for a cost of $1,060 to $1,066 and $1,379 to $1,393, respectively. Conclusion Total costs of tunneled femoral central lines placed in-suite were similar to total costs for lines placed portably. Cost should not be a primary consideration when deciding upon tunneled femoral central line approach in these patients.

Background Ovarian and adnexal cysts are frequently encountered at US examinations performed in preadolescent and adolescent patients, yet there are few published studies regarding the outcomes of cysts in this population. Purpose To identify characteristics at US that help to distinguish physiologic ovarian cysts from nonphysiologic entities. Materials and Methods Female patients who underwent pelvic US with or without Doppler from January 2009 through December 2013 were identified by using a centralized imaging database. Patients older than 7 years and younger than 18 years with ovarian or adnexal cysts at least 2.5 cm were included. Demographic characteristics, date of surgery, surgical notes, and pathologic reports were extracted from the electronic medical record. Initial and follow-up dates of US, cyst size and complexity, imaging diagnosis, and change on subsequent US images were recorded. Statistical analysis was performed with the Wilcoxon rank sum and Kruskal-Wallis tests for continuous variables and the Fisher exact test for categorical variables. Results Of 754 patients who met inclusion criteria (age, 8-18 years; mean age, 14.6 years ± 1.9 [standard deviation]; mean cyst size, 5 cm ± 3.3), 409 patients underwent complete follow-up that included resolution at imaging (n = 250) or surgery (n = 159). In the patients with complete imaging follow-up, mean time to US documentation of resolution was 194 days ± 321; 59.6% (149 of 250) patients had nonsimple cyst characteristics. One-hundred fifty-nine patients underwent surgical intervention (mean cyst size, 8.5 cm ± 5.3), and 69.8% (111 of 159) of the cysts had simple characteristics. Of the 159 cysts, 100 (62.8%) were defined in the pathologic report as paratubal cysts. Of 409 patients, no malignancies were encountered in this study population with surgical or imaging resolution. Conclusion No malignancies were encountered in the study population and the majority of cysts resolved at follow-up imaging. Large size, persistence, and separability from the ovary were most helpful for identification of nonphysiologic paratubal cysts. © RSNA, 2019.

In this article, the fourth author's name is misspelled. The correct spelling, as shown above, should be "Nadia F. Mahmood."

Rationale and Objectives To compare the cost of ultrasound (US) versus magnetic resonance imaging (MRI) using time-driven activity-based costing in adolescent female patients with suspected appendicitis. Materials and Methods Process maps were created using data from electronic medical record review and patient shadowing for adolescent female patients undergoing US or noncontrast MRI exams of the abdomen and pelvis for suspected appendicitis. Capacity cost rates for all personnel, equipment, facilities, and supplies in each exam pathway were established from institutional accounting data. The cost of each process step was determined by multiplying step-specific capacity cost rates by the mean time required to complete the step. Total pathway costs for US and MRI were computed by summing the costs of all steps through each pathway, and a direct cost comparison was made between the two modalities. Results Process maps for US and MRI pathways were generated from 231 and 52 patient encounters, respectively. Patients undergoing US exams followed one of six pathways depending on exam order (abdomen versus pelvis performed first) and whether additional time was needed for bladder filling. Mean total US pathway time was 91 minutes longer than for MRI (US = 166 minutes; MRI = 75 minutes). Total MRI pathway cost was $209.97 compared to a mean US cost of $258.33 (range = $163.21–$293.24). Conclusion MRI can be a faster and less costly alternative to US for evaluating suspected appendicitis in adolescent female patients. While precise costs will vary by institution, MRI may be a viable and at times preferable alternative to US in this patient population.

Ultrasound (US) is the preferred imaging modality for evaluating suspected pediatric appendicitis. However, borderline appendiceal enlargement or questionable inflammatory changes can confound interpretation and lead to equivocal exams. The purpose of this study was to determine which findings on equivocal US exams are most predictive of appendicitis. All US exams performed for suspected pediatric appendicitis from July 1, 2013, through July 9, 2014, were initially interpreted using a risk-stratified scoring system. Two blinded pediatric radiologists independently reviewed US exams designated as equivocal and recorded the following findings: increased wall thickness, loss of mural stratification, peri-appendiceal fat inflammation, peri-appendiceal fluid, appendicolith and maximum appendiceal diameter. A third pediatric radiologist resolved discrepancies. US features were correlated with the final diagnosis via multivariate analysis. During the study period, 162/3,750 (4.3%) children had US exams initially interpreted as equivocal (mean age 9.8 +/- 3.8 years). Five outpatients were lost to follow-up. Forty-eight of the remaining 157 (30.6%) children had an operative diagnosis of appendicitis. Findings significantly associated with appendicitis were loss of mural stratification (odds ratio [OR] = 6.7, P=0.035), peri-appendiceal fat inflammation (OR = 10.0, P

The original version on this paper contained an error. The names of M. John Hicks and R. Paul Guillerman, though correctly appeared in the published version, are incorrectly displayed in indexing sites.

The human disease fibrodysplasia ossificans progressiva (FOP) is a rare and highly disabling disorder of extensive heterotopic bone growth that is caused by a point mutation (R206H) in the activation domain of Alk2, a BMP (bone morphogenic protein) type 1 receptor. The mutation leads to extensive BMP-signaling induced by Activin A, which is normally an antagonist for wildtype receptors, resulting in excessive and uncontrolled bone formation. Here, we studied the effects of Pasteurella multocida toxin (PMT), which activates osteoclasts and inhibits osteoblast activity, in C2C12 myoblasts expressing the mutant Alk2(R206H) receptor as model of FOP. In our study, we mainly used alkaline phosphatase (ALP) activity as marker to determine osteoblast differentiation. BMP-4 stimulated an increase in ALP activity in C2C12-Alk2wt and C2C12-Alk2(R206H) cells. By contrast, Activin A only induced ALP activity in C2C12-Alk2(R206H) cells. In both cases, PMT acted as a potent inhibitor of ALP activity. PMT-induced inhibition of ALP activity was paralleled by a constitutive activation of the heterotrimeric G

Percutaneous renal biopsy is a commonly performed procedure that guides decision-making for children with renal disease. To compare complications from renal biopsies using real-time ultrasound (US) guidance versus pre-procedure US-aided skin-marking in children. We conducted a priori power analysis using a risk-adjusted model, which indicated we needed a sample size of 643–714 procedures (effect size: 0.8). Then we retrospectively identified consecutive patients who underwent a percutaneous renal biopsy from Jan. 1, 2012, to Dec. 31, 2016. We categorized complications according to the Society of Interventional Radiology (SIR) criteria and compared rates using the Fisher exact test. We analyzed complication predictors using multivariate regression. The study consisted of 701 percutaneous renal biopsies in 553 patients: 313 used real-time US guidance and 388 used pre-procedure US-aided skin-marking. Among the 254/701 (36%) complications, 56/313 (18%) resulted from real-time US guidance and 198/388 (51%) from pre-procedure US-aided skin-marking (P

Rationale: In chronic heart failure, increased adrenergic activation contributes to structural remodeling and altered gene expression. Although adrenergic signaling alters histone modifications, it is unknown, whether it also affects other epigenetic processes, including DNA methylation and its recognition. Objective: The aim of this study was to identify the mechanism of regulation of the methyl-CpG–binding protein 2 (MeCP2) and its functional significance during cardiac pressure overload and unloading. Methods and Results: MeCP2 was identified as a reversibly repressed gene in mouse hearts after transverse aortic constriction and was normalized after removal of the constriction. Similarly, MeCP2 repression in human failing hearts resolved after unloading by a left ventricular assist device. The cluster miR-212/132 was upregulated after transverse aortic constriction or on activation of α 1 - and β 1 -adrenoceptors and miR-212/132 led to repression of MeCP2. Prevention of MeCP2 repression by a cardiomyocyte-specific, doxycycline-regulatable transgenic mouse model aggravated cardiac hypertrophy, fibrosis, and contractile dysfunction after transverse aortic constriction. Ablation of MeCP2 in cardiomyocytes facilitated recovery of failing hearts after reversible transverse aortic constriction. Genome-wide expression analysis, chromatin immunoprecipitation experiments, and DNA methylation analysis identified mitochondrial genes and their transcriptional regulators as MeCP2 target genes. Coincident with its repression, MeCP2 was removed from its target genes, whereas DNA methylation of MeCP2 target genes remained stable during pressure overload. Conclusions: These data connect adrenergic activation with a microRNA—MeCP2 epigenetic pathway that is important for cardiac adaptation during the development and recovery from heart failure.

Despite a recent focus on the preferential use of ultrasound over CT for pediatric appendicitis, most children transferred from community hospitals still undergo diagnostic CT scans. The purpose of this study was to evaluate CT techniques performed for children with acute appendicitis at nonpediatric treatment centers.All patients treated for acute appendicitis at our tertiary-care pediatric hospital from July 1, 2011, through June 30, 2012, were identified. Patient demographics, imaging modality used to diagnoses appendicitis (CT or ultrasound), location (home or referral institution), and CT technique parameters were collected. The estimated mean organ radiation dose, number of imaging phases, and use of contrast media were evaluated at home and referral institutions.During the study period, 1215 patients underwent appendectomies after imaging, with 442 (36.4%) imaged at referral facilities. Most referral patients received a diagnosis by CT (n=384, 87%), compared with 73 of 773 (9.4%) who received a diagnosis by CT at the home institution. The estimated mean (±SD) organ radiation dose was not statistically significantly different between home and referral institutions (13.5±7.3 vs 12.9±6.4 mGy; p=0.58) for single-phase examinations. Of 384 referral patients, 344 had images available for review. In total, 40% (138/344) of patients from referral centers were imaged with suboptimal CT techniques: 50 delayed phase only, 52 dual phase (eight of which were imaged twice in delayed phase), eight triple phase, and 36 without IV contrast agent.CT parameters and radiation doses from single-phase examinations in children with appendicitis were similar at nonpediatric treatment centers and a tertiary care children's hospital. Future educational outreach should focus on optimizing other technical parameters.

Pasteurella multocida toxin (PMT) persistently activates heterotrimeric G proteins of the Gαq/11 , Gα12/13 and Gαi family without interaction with G protein-coupled receptors (GPCRs). We show that PMT acts on heart tissue in vivo and on cardiomyocytes and cardiac fibroblasts in vitro by deamidation of heterotrimeric G proteins. Increased normalized ventricle weights and fibrosis were detected after intraperitoneal administration of PMT in combination with the GPCR agonist phenylephrine. In neonatal rat cardiomyocytes, PMT stimulated the mitogen-activated protein kinase pathway, which is crucial for the development of cellular hypertrophy. The toxin induced phosphorylation of the canonical phosphorylation sites of the extracellular-regulated kinase 1/2 and, additionally, caused phosphorylation of the recently recognized autophosphorylation site, which appears to be important for the development of cellular hypertrophy. Moreover, PMT stimulated the small GTPases Rac1 and RhoA. Both switch proteins are involved in cardiomyocyte hypertrophy. In addition, PMT stimulated RhoA and Rac1 in neonatal rat cardiac fibroblasts. RhoA and Rac1 have been implicated in the regulation of connective tissue growth factor (CTGF) secretion and expression. Accordingly, we show that PMT treatment increased secretion and expression of CTGF in cardiac fibroblasts. Altogether, the data indicate that PMT is an inducer of pathological remodelling of cardiac cells and identifies the toxin as a promising tool for studying heterotrimeric G protein-dependent signalling in cardiac cells.

Purpose The proliferation of pediatric urgent care centers has increased the need for diagnostic imaging support, but the impact of employing radiology technologists at these centers is not known. The purpose of this study was to evaluate radiographic impact and quality at urgent care centers with and without radiology technologists. Methods A retrospective case-control study was conducted comparing 235 radiographic examinations (study) performed without and 83 examinations (control) performed with a radiology technologist at the authors' pediatric urgent care centers. Studies were evaluated for quality using a five-point, Likert-type scale (1 = poor, 5 = best) regarding field of view, presentation, and orthogonal view orientation. Studies were also evaluated for the incidence of positive results, need for repeat imaging, and discrepancies between initial study and follow-up. Results Imaging quality comparisons between study and control groups were statistically different for field of view (3.98 versus 4.29, P = .014), presentation (4.39 versus 4.51, P = .045), and orthogonal view orientation (4.45 versus 4.69, P = .033). The incidence of repeat imaging was similar (4.7% versus 2.4%, P = 0.526), as well as the discrepancy rates (3.4 versus 2.4%, P = 1.00). The incidence of abnormal radiographic findings for the study and control groups was similar (40.9% versus 34.9%, P = .363). Conclusions Radiography is an important triage tool at pediatric urgent care centers. It is imperative to have optimal radiographic imaging for accurate diagnosis, and imaging quality is improved when radiology technologists are available. If not feasible or cost prohibitive, it is important that physicians be given training opportunities to bridge the quality gap when using radiographic equipment and exposing children to radiation.

PURPOSE The aim of this study was to analyze the feasibility and diagnostic performance of F-FDG PET/MR compared with F-FDG PET/CT in a cohort of pediatric histiocytosis patients with regard to image quality, lesion detection, and FDG quantification. METHODS Children with a diagnosis of Langerhans cell histiocytosis or Rosai-Dorfman disease were prospectively recruited. Seventeen PET/CT and PET/MR examinations were performed on 9 patients (mean age, 6.2 years) following a single-injection dual-imaging protocol. The indication was Langerhans cell histiocytosis in 10 examinations and Rosai-Dorfman disease in 7 examinations. The anonymized data were evaluated for image quality and lesion detection. SUV quantification of each lesion was compared between modalities. RESULTS All PET/MR examinations had good or excellent image quality and were deemed clinically acceptable. There was substantial agreement of PET image quality among readers of PET/MR images. Per patient, PET/MR and PET/CT had complete concordance in identifying active disease. PET/MRI correctly classified 74 (96%) of 77 foci of disease identified on PET/CT. The per-lesion maximum SUVs were strongly correlated between modalities with a Spearman correlation coefficient of 0.73 (P < 0.001). CONCLUSIONS The use of PET/MR is clinically feasible in pediatric patients with a histiocytic disease. PET/MR demonstrates comparable image quality and lesion detection to PET/CT while maintaining strongly correlated quantitative performance. Given the significant radiation dose savings, PET/MR represents an appealing alternative to PET/CT in the care of children with histiocytic disorders.

Renewable based distributed generation (DG) particularly in low voltage (LV) distribution networks may cause voltage limit violations, line overloads and increase in network losses. Siting and sizing of DG penetrations are generally done according to the worst case scenarios. However, since these cases occur rarely in long term operation, a realistic design enables more DG penetration. There are numerous conventional methods, each having several benefits and drawbacks. Local energy management systems can also be part of the solution. This study investigates the negative steady state operational impacts of DG on LV distribution networks and proposes a microgrid management approach to mitigate those impacts. A field data-based virtual test bed is used to simulate undervoltage and overvoltage issues and a microgrid energy management approach is developed and tested to minimize the negative impacts on the network. Moreover, Digital Audio Broadcasting (DAB) as data transmission means in microgrids, is discussed as an adaptable communication solution for its real-world implementation.

The AB-type protein toxin from Pasteurella multocida (PMT) contains a functionally important disulfide bond within its catalytic domain, which must be cleaved in the host cell cytosol to render the catalytic domain of PMT into its active conformation. Here, we found that the reductive potential of the cytosol of target cells, and more specifically, the activity of the thioredoxin reductase (TrxR) is crucial for this process. This was demonstrated by the strong inhibitory effect of the pharmacological TrxR inhibitor auranofin, which inhibited the intoxication of target cells with PMT, as determined by analyzing the PMT-catalyzed deamidation of GTP-binding proteins (G-proteins) in the cytosol of cells. The amount of endogenous substrate levels modified by PMT in cells pretreated with auranofin was reduced compared to cells treated with PMT alone. Auranofin had no inhibitory effect on the activity of the catalytic domain of constitutively active PMT in vitro, demonstrating that auranofin did not directly inhibit PMT activity, but interferes with the mode of action of PMT in cells. In conclusion, the results show that TrxR is crucial for the mode of action of PMT in mammalian cells, and that the drug auranofin can serve as an efficient inhibitor, which might be a starting point for novel therapeutic options against toxin-associated diseases., publishedVersion

SummaryBacterial components are recognized by the immune system through activation of the inflammasome, eventually causing processing of the proinflammatory cytokine interleukin-1β (IL-1β), a pleiotropic cytokine and one of the most important mediators of inflammation, through the protease caspase-1. Synthesis of the precursor protein and processing into its bioactive form are tightly regulated, given that disturbed control of IL-1β release can cause severe autoinflammatory diseases or contribute to cancer development. We show that the bacterial Pasteurella multocida toxin (PMT) triggers Il1b gene transcription in macrophages independently of Toll-like receptor signaling through RhoA/Rho-kinase-mediated NF-κΒ activation. Furthermore, PMT mediates signal transducer and activator of transcription (STAT) protein-controlled granzyme A (a serine protease) expression in macrophages. The exocytosed granzyme A enters target cells and mediates IL-1β maturation independently of caspase-1 and without inducing cytotoxicity. These findings show that macrophages can induce an IL-1β-initiated immune response independently of inflammasome activity.

Background Gastrostomy tubes are often dislodged or exchanged in children. Indications for fluoroscopic examination of gastrostomy location include concern for malposition, dislodgement, leak, or gastric outlet obstruction. We hypothesized that most of the studies obtained at our institution were not ordered for one of the aforementioned indications and do not ultimately affect patient management. Methods All fluoroscopic gastrostomy studies performed from January 2011 to December 2012 were reviewed. Transgastric jejunostomy studies were excluded. Patient demographics, indications for the study, elapsed time since placement, imaging findings, and short-term outcomes were recorded. Chi-square analysis was used to evaluate relationships between categorical variables. Results During the study period, 337 patients who underwent fluoroscopic gastrostomy studies were identified; median age was 2.5 y (0.05–23.8). Sixty-two percent (208/337) of the studies were ordered in asymptomatic patients to confirm tube placement location after routine exchange or replacement. Symptomatic patients accounted for 38% of the studies. Ordering physicians were primarily nonsurgeons (72%, 242/337). Abnormal findings were observed in 4.8% (16/337) of patients, six (1.7%) of whom required an operative intervention. The 2.9% (6/208) abnormal study rate for asymptomatic patients was significantly lower than the 7.9% (10/129) rate in the patients who were evaluated for symptomatic indications (P = 0.03). Conclusions Most of the fluoroscopic gastrostomy studies ordered at a tertiary care center did not appear to alter patient care. Development of a standardized management algorithm based on clinical indications is necessary to decrease the number of extraneous gastrostomy studies.

The purpose of this study was to characterize the extent of joint and tendon involvement in patients with juvenile idiopathic arthritis referred for MRI of the wrist or ankle.Forty-five patients (32 female and 13 male patients; mean age, 10 years; age range, 1-19 years) with an established diagnosis of juvenile idiopathic arthritis were referred for MRI of the wrist or ankle between January 2000 and August 2012 (39 wrists and 33 ankles). All MRI examinations and clinical notes were reviewed, and joint and tendon involvement was recorded.Tenosynovitis was present in 50% (36/72) of examinations. Tenosynovitis was not documented in clinical notes before MRI. When tenosynovitis was present, an average of 3.5 tendons were involved (range, 1-12 tendons). For the wrist, 59% (23/39) had tenosynovitis, and the extensor digitorum tendon (23% [9/39]) was most commonly involved. For the ankle, 39% (13/33) had tenosynovitis, and the tibialis posterior tendon (33.3% [11/33]) was most commonly involved. For the wrist, 89.7% (35/39) had active joint inflammation with an average of 3.1 joints involved (range, 0-6 joints), and the intercarpal joint was most commonly involved (69% [27/39]). For the ankle, 69.7% (23/33) had active joint inflammation, with an average of 2.4 joints involved (range, 0-5 joints), and the tibiotalar joint (52% [17/33]) was most commonly involved.Multicompartmental tenosynovitis and arthritis involvement is common in patients with juvenile idiopathic arthritis referred for MRI of the wrist or ankle and is underappreciated on clinical examination. International League of Associations for Rheumatology subclassification and targeted intraarticular steroid injections guided by clinical examination alone may lead to undertreatment or incorrect treatment of active disease.

Many galactic and extragalactic astrophysical sources are currently considered promising candidates as high energy neutrino emitters. Astrophysical neutrinos can be detected as upward-going muons produced in charged-current interactions with the medium surrounding the detector. The expected neutrino fluxes from various models start to dominate on the atmospheric neutrino background at neutrino energies above some tens of TeV. We present the results of a search for an excess of high energy upward-going muons among the sample of data collected by MACRO during ~5.8 years of effective running time. No significant evidence for this signal was found. As a consequence, an upper limit on the flux of upward-going muons from high-energy neutrinos was set at the level of 1.7 10^(-14) cm^(-2) s^(-1) sr^(-1). The corresponding upper limit for the diffuse neutrino flux was evaluated assuming a neutrino power law spectrum. Our result was compared with theoretical predictions and upper limits from other experiments., 19 pages, 8 figures, 2 tables

A new bacterial toxin from pathogen Photorhabdus asymbiotica is now described. The toxin contains a domain with glycosyltransferase activity that modifies a tyrosine residue of Rho GTPases in the host cell, inhibiting Rho activation and interaction with downstream effectors. The second domain is a glutamine deamidase that blocks GTP hydrolysis by Gaq/11 and Gai proteins. Entomopathogenic Photorhabdus asymbiotica is an emerging pathogen in humans. Here, we identified a P. asymbiotica protein toxin (PaTox), which contains a glycosyltransferase and a deamidase domain. PaTox mono-O-glycosylates Y32 (or Y34) of eukaryotic Rho GTPases by using UDP–N-acetylglucosamine (UDP-GlcNAc). Tyrosine glycosylation inhibits Rho activation and prevents interaction with downstream effectors, resulting in actin disassembly, inhibition of phagocytosis and toxicity toward insects and mammalian cells. The crystal structure of the PaTox glycosyltransferase domain in complex with UDP-GlcNAc determined at 1.8-A resolution represents a canonical GT-A fold and is the smallest glycosyltransferase toxin known. 1H-NMR analysis identifies PaTox as a retaining glycosyltransferase. The glutamine-deamidase domain of PaTox blocks GTP hydrolysis of heterotrimeric Gαq/11 and Gαi proteins, thereby activating RhoA. Thus, PaTox hijacks host GTPase signaling in a bidirectional manner by deamidation-induced activation and glycosylation-induced inactivation of GTPases.

The protein toxin Pasteurella multocida toxin (PMT) is the causative agent of atrophic rhinitis in pigs, leading to atrophy of the nasal turbinate bones by affecting osteoblasts and osteoclasts. The mechanism of PMT-induced intoxication is a deamidation of α-subunits of heterotrimeric G proteins, including Gα q , Gα 13 , and Gα i , thereby causing persistent activation of the G proteins. Here we utilized PMT as a transporter of the non-cell-permeating A domain of diphtheria toxin (DTa). Fusion proteins of PMT and DTa ADP-ribosylated elongation factor 2, the natural target of diphtheria toxin, leading to cell toxicity. PMT-DTa effects were competed by PMT, indicating binding to the same cell surface receptor. Fluorescently labeled PMT-DTa and PMT colocalized with specific markers of early and late endosomes. Bafilomycin A, which inhibits vacuolar H + -ATPase, blocked PMT-DTa-induced intoxication of HEK-293 cells. By constructing various PMT-DTa chimeras, we identified a minimal region of PMT necessary for uptake of DTa. The data suggest that PMT is able to transport cargo proteins into eukaryotic cells by utilizing the PMT-specific uptake route.