Shelia Salisbury

Sirolimus for Angiomyolipoma in Tuberous Sclerosis Complex or Lymphangioleiomyomatosis

BACKGROUND Angiomyolipomas in patients with the tuberous sclerosis complex or sporadic lymphangioleiomyomatosis are associated with mutations in tuberous sclerosis genes resulting in constitutive activation of the mammalian target of rapamycin (mTOR). The drug sirolimus suppresses mTOR signaling. METHODS We conducted a 24-month, nonrandomized, open-label trial to determine whether sirolimus reduces the angiomyolipoma volume in patients with the tuberous sclerosis complex or sporadic lymphangioleiomyomatosis. Sirolimus was administered for the first 12 months only. Serial magnetic resonance imaging of angiomyolipomas and brain lesions, computed tomography of lung cysts, and pulmonary-function tests were performed. RESULTS Of the 25 patients enrolled, 20 completed the 12-month evaluation, and 18 completed the 24-month evaluation. The mean (+/-SD) angiomyolipoma volume at 12 months was 53.2+/-26.6% of the baseline value (P<0.001) and at 24 months was 85.9+/-28.5% of the baseline value (P=0.005). At 24 months, five patients had a persistent reduction in the angiomyolipoma volume of 30% or more. During the period of sirolimus therapy, among patients with lymphangioleiomyomatosis, the mean forced expiratory volume in 1 second (FEV1) increased by 118+/-330 ml (P=0.06), the forced vital capacity (FVC) increased by 390+/-570 ml (P<0.001), and the residual volume decreased by 439+/-493 ml (P=0.02), as compared with baseline values. One year after sirolimus was discontinued, the FEV1 was 62+/-411 ml above the baseline value, the FVC was 346+/-712 ml above the baseline value, and the residual volume was 333+/-570 ml below the baseline value; cerebral lesions were unchanged. Five patients had six serious adverse events while receiving sirolimus, including diarrhea, pyelonephritis, stomatitis, and respiratory infections. CONCLUSIONS Angiomyolipomas regressed somewhat during sirolimus therapy but tended to increase in volume after the therapy was stopped. Some patients with lymphangioleiomyomatosis had improvement in spirometric measurements and gas trapping that persisted after treatment. Suppression of mTOR signaling might constitute an ameliorative treatment in patients with the tuberous sclerosis complex or sporadic lymphangioleiomyomatosis. (ClinicalTrials.gov number, NCT00457808.)

National Trends in CT Use in the Emergency Department: 1995-2007

PURPOSE To identify nationwide trends and factors associated with the use of computed tomography (CT) in the emergency department (ED). MATERIALS AND METHODS This study was exempt from institutional review board approval. Data from the 1995-2007 National Hospital Ambulatory Medical Care Survey were used to evaluate the numbers and percentages of ED visits associated with CT. A mean of 30 044 visits were sampled each year. Data were also subcategorized according to multiple patient and hospital characteristics. The Rao-Scott χ(2) test was performed to determine whether CT use was similar across subpopulations. Data were evaluated according to exponential and logistic growth models. RESULTS From 1995 to 2007, the number of ED visits that included a CT examination increased from 2.7 million to 16.2 million, constituting a 5.9-fold increase and a compound annual growth rate of 16.0%. The percentage of visits associated with CT increased from 2.8% to 13.9%, constituting a 4.9-fold increase and a compound annual growth rate of 14.2%. The exponential growth model provided the best fit for the trend in CT use. CT use was greater in older patients, white patients, patients admitted to the hospital, and patients at facilities in metropolitan regions. By the end of the study period, the top chief complaints among those who underwent CT were abdominal pain, headache, and chest pain. The percentage of patient visits associated with CT for all evaluated chief complaints increased-most substantially among those who underwent CT for flank, abdominal, or chest pain. CONCLUSION Use of CT has increased at a higher rate in the ED than in other settings. The overall use of CT had not begun to taper by 2007.

Rising Use of CT in Child Visits to the Emergency Department in the United States, 1995–2008

PURPOSE To describe nationwide trends and factors associated with the use of computed tomography (CT) in children visiting emergency departments (EDs) in the United States between 1995 and 2008. MATERIALS AND METHODS This study was exempt from institutional review board oversight. Data from the 1995-2008 National Hospital Ambulatory Medical Care Survey were used to evaluate the number and percentage of visits associated with CT for patients younger than 18 years. A mean of 7375 visits were sampled each year. Data were subcategorized according to multiple patient and hospital characteristics. The Rao-Scott χ(2) test was performed to determine whether CT use was similar across subpopulations. RESULTS From 1995 to 2008, the number of pediatric ED visits that included CT examination increased from 0.33 to 1.65 million, a fivefold increase, with a compound annual growth rate of 13.2%. The percentage of visits associated with CT increased from 1.2% to 5.9%, a 4.8-fold increase, with a compound annual growth rate of 12.8%. The number of visits associated with CT at pediatric-focused and non-pediatric-focused EDs increased from 14,895 and 316,133, respectively, in 1995 to 212,716 and 1,438,413, respectively, in 2008. By the end of the study period, top chief complaints among those undergoing CT included head injury, abdominal pain, and headache. CONCLUSION Use of CT in children who visit the ED has increased substantially and occurs primarily at non-pediatric-focused facilities. This underscores the need for special attention to this vulnerable population to ensure that imaging is appropriately ordered, performed, and interpreted.

Effectiveness of Pentavalent Rotavirus Vaccine Against Severe Disease

OBJECTIVE: To determine the vaccine effectiveness (VE) of complete and partial vaccination with the pentavalent rotavirus vaccine (RV5) in the prevention of rotavirus acute gastroenteritis (AGE) hospitalizations and emergency department visits during the first 3 rotavirus seasons after vaccine introduction. METHODS: Active, prospective population-based surveillance for AGE and acute respiratory infection (ARIs) in inpatient and emergency department settings provided subjects for a case-control evaluation of VE in 3 US counties from January 2006 through June 2009. Children with laboratory-confirmed rotavirus AGE (cases) were matched according to date of birth and onset of illness to 2 sets of controls: children with rotavirus-negative AGE and children with ARI. The main outcome measure was VE with complete (3 doses) or partial (1 or 2 doses) RV5 vaccination. RESULTS: Of age-eligible children enrolled, 18% of cases, 54% of AGE controls, and 54% of ARI controls received ≥1 dose of RV5. The VE of RV5 for 1, 2, and 3 doses against all rotavirus genotypes with the use of rotavirus-negative AGE controls was 74% (95% confidence interval [CI]: 37%–90%), 88% (95% CI: 66%–96%), and 87% (95% CI: 71%–94%), respectively, and with the use of ARI controls was 73% (95% CI: 43%–88%), 88% (95% CI: 68%–95%), and 85% (95% CI: 72%–91%), respectively. The overall VE estimates were comparable during the first and second years of life and against AGE caused by different rotavirus strains. CONCLUSION: RV5 was highly effective in preventing severe rotavirus disease, even after a partial series, with protection persisting throughout the second year of life.

Cardiovascular Anomalies in Turner Syndrome: Spectrum, Prevalence, and Cardiac MRI Findings in a Pediatric and Young Adult Population

OBJECTIVE Turner syndrome affects one in 2,500 girls and women and is associated with cardiovascular anomalies. Visualizing the descending thoracic aorta in adults with Turner syndrome with echocardiography is difficult. Therefore, cardiac MRI is the preferred imaging modality for surveillance. Our goals were to use cardiac MRI describe the spectrum and frequency of cardiovascular abnormalities and to evaluate aortic dilatation and associated abnormalities in pediatric patients with Turner syndrome. MATERIALS AND METHODS The cases of 51 patients with Turner syndrome (median age, 18.4 years; range, 6-36 years) were evaluated with cardiac MRI. The characteristics assessed included aortic structure, elongation of the transverse aortic arch, aortic diameter at multiple locations, and coarctation of the aorta (CoA). Additional evaluations were made for presence of bicuspid aortic valve (BAV), and partial anomalous pulmonary venous return (PAPVR). Associations between the cardiac MRI data and the following factors were assessed: age, karyotype, body surface area, blood pressure, and ventricular sizes and function. RESULTS Sixteen patients (31.4%) had elongation of the transverse aortic arch, eight (15.7%) had CoA, 20 (39.2%) had BAV, and eight (15.7%) had PAPVR. Aortic dilatation was most common at the aortic sinus (30%). Elongation of the transverse aortic arch was associated with CoA (p < 0.01) and BAV (p < 0.05). Patients with elongation of the transverse aortic arch had dilated aortic sinus (p < 0.05). Patients with PAPVR had increased right heart mass (p < 0.05), increased ratio of main pulmonary artery to aortic valve blood flow (p = 0.0014), and increased right ventricular volume (p < 0.05). CONCLUSION Cardiovascular anomalies in pediatric patients with Turner syndrome include aortic abnormalities and PAPVR. The significant association between elongation of the transverse aortic arch and CoA, BAV, and aortic sinus dilatation may contribute to increased risk of aortic dissection. The presence of PAPVR can be hemodynamically significant. These findings indicate that periodic cardiac MRI screening of persons with Turner syndrome is beneficial.

Effect of increasing depth of dexmedetomidine and propofol anesthesia on upper airway morphology in children and adolescents with obstructive sleep apnea

STUDY OBJECTIVE To examine the dose-response effects of dexmedetomidine (DEX) and propofol (PROP) on airway morphology in children and adolescents with a history of obstructive sleep apnea (OSA). DESIGN Prospective, single-blinded, controlled comparative study. SETTING University-affiliated teaching hospital. PATIENTS 60 patients with a history of OSA who presented for a magnetic resonance imaging (MRI) sleep study. INTERVENTIONS Patients were randomized to two equal groups (DEX or PROP). Magnetic resonance images of the airway were obtained during low (1 μg/kg/hr) and high (3 μg/kg/hr) doses of DEX, or low (100 μg/kg/m) and high (200 μg/kg/m) doses of PROP, based on group assignment. MEASUREMENTS The airway anteroposterior (AP) diameter, transverse diameter, and sectional areas were measured at the level of the nasopharyngeal airway and retroglossal airway. The influence of the two drugs and OSA severity, as determined by polysomnography, on airway dimensions was examined using mixed-effects analysis of covariance models. MAIN RESULTS Upper airway morphology was completed in 45 patients. Most airway measurements showed statistically nonsignificant associations with increasing doses of PROP and DEX. As the dosage increased, average airway dimensions were typically unchanged or slightly increased with DEX compared with airway dimensions that were unchanged or slightly decreased with PROP. An airway intervention was required in three children (11%) in the DEX group and 7 children (23%) in the PROP group (P = NS). CONCLUSIONS Both agents provided an acceptable level of anesthesia for MRI sleep studies in patients with OSA, with statistically nonsignificant changes in airway dimensions.

Susceptibility of Transcranial Electric Motor-evoked Potentials to Varying Targeted Blood Levels of Dexmedetomidine during Spine Surgery

Background:Dexmedetomidine has been increasingly used as an adjunct to opioid–propofol total intravenous anesthesia (TIVA). The authors tested the hypothesis and found that clinically relevant blood levels of dexmedetomidine do not produce significant attenuation of the amplitude of transcranial electric motor-evoked potentials either independently or by interaction with propofol in a dose-dependent manner. Methods:The authors planned to recruit 72 patients with idiopathic scoliosis who had posterior spine fusion surgery during propofol and remifentanil TIVA with dexmedetomidine as an adjunct. However, the authors terminated the study after enrolling 44 patients because of change in surgical technique. Before administering dexmedetomidine, baseline transcranial electric motor-evoked potentials were acquired during TIVA with remifentanil and propofol. Patients were randomized to varying targeted blood levels of dexmedetomidine (0.4, 0.6, and 0.8 ng/ml) and propofol (2.5, 3.75, and 5 &mgr;g/ml) using a factorial design. The primary outcome variable was amplitude of transcranial electric motor-evoked potential. The secondary outcome was amplitude of cortical somatosensory-evoked potentials. Results:Of the 44 recruited patients, 40 completed the study, and their data were analyzed. The administration of dexmedetomidine in increasing doses as an adjunct to propofol-based TIVA caused a clinically and statistically significant attenuation of amplitudes of transcranial electric motor-evoked potentials. Conclusion:The authors conclude that under the stimulation conditions used, dexmedetomidine as an anesthetic adjunct to propofol-based TIVA at clinically relevant target plasma concentrations (0.6–0.8 ng/ml) can significantly attenuate the amplitude of transcranial electric motor-evoked potentials.

Operating Room Traffic: Is There Any Role of Monitoring It?

Background Operating room (OR) human traffic has been implicated as a cause of surgical site infection. We first observed the normal human traffic pattern in our Pediatric Orthopedic ORs, and then examined the effect of surveillance on that traffic pattern. Methods This study consisted of 2 phases: phase I sought to observe the OR traffic pattern (number of door swings, maximum and minimum number of OR personnel, number of OR personnel at 30-minute intervals, or changes in nursing, anesthesia, or surgeon staff) during surgical cases without OR personnel being notified, and for phase II, the same traffic pattern was monitored with their knowledge. Results Two thousand four hundred forty-two minutes of surgical time were observed in phase I, and 1908 minutes were observed in phase II. There was no difference (P=0.06) in the time between door swings between phase I (1.39 min) and phase II (1.70 min), no difference (P=1.000) in the maximum number of people in the OR between phase I (11.5 people, range: 7-15 people) and phase II (11.5 people, range: 8-20 people), and no difference (P=1.000) in the minimum number of people in the OR between phase I (4.67 people, range: 4-6 people) and phase II (4.71 people, range: 3-6 people). There was a difference in the time between door swings (P=0.03) and maximum number of people in the OR (P=0.005) based on the length of the surgery (less or more than 120 min). There was no difference in the time between door swings (P=0.11), but there was a difference in the maximum number of people in the OR (P=0.002) based on type of surgery (spine vs. others). Conclusions There was no role of surveillance of human traffic in the OR. To achieve any change in the OR traffic pattern, monitoring alone may not be sufficient; other novel techniques or incentives may need to be considered.

Congenital lung lesions: prenatal MRI and postnatal findings

BackgroundCongenital lung lesions refer to a spectrum of malformations and developmental abnormalities of the foregut, pulmonary airways and vasculature. These lesions range from small, asymptomatic to large space-occupying masses that can increase risk of fetal death and respiratory compromise after birth. Prenatal sonography has been used for routine screening in pregnancy. The advent of prenatal magnetic resonance imaging leads to complementary use in the diagnosis of fetal anomalies, including in fetuses with congenital lung lesions.ObjectiveTo determine whether fetal MRI can differentiate congenital lung lesions by comparing prenatal diagnosis with postnatal imaging and pathology.Materials and methodsIn a 4-year period, 76 fetuses with suspected lung lesions were referred for fetal MRI. We retrospectively reviewed the MR exams and assigned a specific diagnosis based on predetermined criteria. We then compared the prenatal diagnosis to postnatal imaging and pathology.ResultsOf 76 cases, 7 were excluded because of an alternative diagnosis. Of the 69 remaining patients, 3 died and 13 were lost to follow-up. Among the 53 patients, there were 56 lung lesions. Four of these lesions were difficult to diagnose because of size and location. Based on imaging records we gave the remaining 52 lesions a specific prenatal diagnosis: 28 congenital pulmonary airway malformations (CPAM), 4 bronchopulmonary sequestrations (BPS), 9 cases of overinflation, 9 hybrid lesions and 2 bronchogenic cysts. The prenatal diagnosis was concordant with postnatal evaluation in 51 of the 52 lung lesions. One fetus given the diagnosis of CPAM prenatally was diagnosed with a hybrid lesion postnatally.ConclusionPrenatal MRI is highly accurate in defining congenital lung anomalies. When fetal MRI findings suggest a specific diagnosis, postnatal findings confirmed the prenatal MRI diagnosis in 98% of cases.

Intestinal Parasite Screening in Internationally Adopted Children: Importance of Multiple Stool Specimens

OBJECTIVE: Our goal was to determine the prevalence of intestinal parasites in internationally adopted children, to examine factors associated with infection, and to determine if evaluating multiple stool specimens increases the yield of parasite identification. METHODS: We evaluated internationally adopted children with at least 1 stool specimen submitted for ova and parasite testing within 120 days after arrival to the United States. In children submitting 3 stool specimens, in which at least 1 specimen was positive for the pathogen studied, we examined whether multiple stool specimens increased the likelihood of pathogen identification. RESULTS: Of the 1042 children studied, 27% had at least 1 pathogen identified; with pathogen-specific prevalence of Giardia intestinalis (19%), Blastocystis hominis (10%), Dientamoeba fragilis (5%), Entamoeba histolytica (1%), Ascaris lumbricoides (1%), and Hymenolepsis species (1%). The lowest prevalence occurred in South Korean (0%), Guatemalan (9%), and Chinese (13%) children, and the highest prevalence occurred in Ethiopian (55%) and Ukrainian (74%) children. Increasing age was significantly associated with parasite identification, whereas malnutrition and gastrointestinal symptoms were not. Overall, the yield of 1 stool specimen was 79% with pathogen recovery significantly increasing for 2 (92%) and 3 (100%) specimens, respectively (P < .0001). Pathogen identification also significantly increased with evaluation of additional stool specimens for children with and without gastrointestinal symptoms. CONCLUSIONS: We provide data for evidence-based guidelines for intestinal parasite screening in internationally adopted children. Gastrointestinal symptoms were not predictive of pathogen recovery, and multiple stool specimens increased pathogen identification in this high-risk group of children.